# Public copy: quotes from papers without an open licence are withheld (see notes). excerpts: - edge: - hyperadrenergic_evidence - proposed_mechanism_of - pots papers: 168 evidence: - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: The cause of POTS is complex but includes partial autonomic neuropathy, hypovolemia, hyperadrenergic states (elevated plasma norepinephrine levels), and impaired venous return [5]. note: 'Found by winnow, kev and lev in p028, p029, p015. Claude judged: supports.' - paper: pmid42060631 cited: true text: full license: by verdict: supports section: Discussion quote: Furthermore, the development of primary idiopathic POTS is thought to be related to multiple mechanisms, including viral illness (or any condition that activates the innate immune response); peripheral nerve denervation with hypersensitivity; α-receptor hypersensitivity; autoantibodies to acetylcholine and β-receptors; central hyperadrenergic state; norepinephrine transporter deficiency; reduced baroreceptor gain; idiopathic hypovolemia with changes in aldosterone, renin, neuronal nitric oxide synthase, and angiotensin II activities; autoimmune reactions; mast cell activation; and decreased heart size and mass [38–51]. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid41767063 cited: true text: full license: by verdict: supports section: Background quote: 'According to current evidence, POTS is a subtype of a cardiovascular autonomic dysregulation, characterized by three distinct mechanisms: hypovolemic, hyperadrenergic and neuropathic subtypes [6]. Proposed mechanisms include disorders of autonomic cardiovascular regulation, involving both abnormally increased sympathetic activity and peripheral sympathetic denervation leading to central hypovolemia.' note: 'Found by winnow, kev and lev in p004, p010, p019. Claude judged: supports.' - paper: pmid41538594 cited: true text: full license: by verdict: supports section: Introdução quote: 'São conhecidos três mecanismos fisiopatológicos que podem resultar em fenótipos distintos de POTS: neuropatia autonômica parcial, hipovolemia persistente e estado hiperadrenérgico central e que podem coexistir nos pacientes portadores de POTS.' note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid41533304 cited: true text: full license: by verdict: supports section: Introduction quote: In a subset of these patients, the main pathophysiological mechanism has been proposed to be primary sympathetic activation (hyperadrenergic POTS) [2, 3]. note: 'Found by winnow, kev and lev in p001, p004, p006. Claude judged: supports.' - paper: pmid41314719 cited: true text: full license: by verdict: supports section: Abstract quote: Emerging evidence suggests that trauma-related dysregulation of the autonomic nervous system may manifest as POTS, with hypervigilance and hyperadrenergic states proposed as potential mechanisms. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid41163092 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: A number of mechanisms have been described in patients with POTS, including autonomic dysfunction (AD), hypovolemia, hyper-adrenergic stimulation, deconditioning, anxiety and hypervigilance [7, 8]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid41103515 cited: true text: full license: by verdict: supports section: Differential diagnosis of OD with PPPD > Hemodynamic orthostatic dizziness > Postural orthostatic tachycardia syndrome quote: The pathophysiology of POTS is complex and diverse. Potential causes include a partially denervated circulatory system, a hyperadrenergic state, hypovolemia, peripheral blood pooling, or prolonged bed rest (15). note: 'Found by winnow, kev and lev in p009, p010. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 4 Discussion quote: Hypotheses regarding pathophysiology include abnormally increased sympathetic activity, sympathetic denervation leading to hypovolemia and reflex tachycardia, and autoimmunity to G-protein coupled receptors (2, 3, 79, 81, 82). note: 'Found by winnow, kev and lev in p026, p024. Claude judged: supports.' - paper: pmid40776616 cited: true text: full license: by-nc verdict: supports section: Discussion quote: However, POTS is a cardiovascular autonomic disorder that differs from VVS. It is caused by a complex interaction of cardiac receptor-activating autoantibodies, hyperadrenergic activation, hypovolemia, and partial autonomic neuropathy [8,24-26], with impairment of cerebrovascular autoregulation being an important pathogenic mechanism. note: 'Found by winnow, kev and lev in p028, p030. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Introduction quote: The precise pathophysiology of POTS is not fully understood but several factors may contribute, including hyperadrenergic stimulation, hypovolemia, peripheral autonomic neuropathy, and autoimmunity.6 note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40626134 cited: true text: full license: by verdict: supports section: Abstract quote: Central hypovolemia, peripheral vascular dysfunction, and a hyperadrenergic state may contribute to the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p003, p001. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Investigations have demonstrated that patients with POTS commonly present orthostatic tachycardia owing to SNS hyperactivation [2–4]. These patients typically show elevated SNS activity and diminished parasympathetic activity in the evaluation of autonomic function testing, resulting in a substantial increase in HR [7,13]. note: 'Found by winnow, kev and lev in p004, p005, p028. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: In this study, patients with POTS after HSCT exhibited a significantly greater increase in NE levels upon standing, indicating heightened sympathetic activation. NE changes also correlated with changes in HR, supporting a central role for adrenergic signaling in post-HSCT POTS. note: 'Found by winnow, kev and lev in p004, p032, p033. Claude judged: supports.' - paper: pmid40507411 cited: true text: full license: by verdict: supports section: 4. Discussion quote: 'The consensus meeting of the NIH identified multiple pathophysiological mechanisms leading to orthostatic intolerance and POTS [49]: hypovolemia, deconditioning, inflammatory mediators, excessive sympathetic stimulation, auto-antibodies, small-fiber neuropathy, and connective tissue laxity.' note: 'Found by winnow, kev and lev in p020, p022. Claude judged: supports.' - paper: pmid40432440 cited: true text: full license: by verdict: supports section: Introduction quote: POTS etiology is heterogeneous. Multiple mechanisms have been considered responsible for the development of POTS - peripheral denervation, hyperadrenergic state, hypovolemia, viral illness, mast cell activation, and, recently immune dysregulation [5,6]. note: 'Found by winnow, kev and lev in p034, p005. Claude judged: supports.' - paper: pmid40294227 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40294227. Found by winnow, kev and lev in p003, p011, p001. Claude judged: supports.' - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: The increase of catecholamine is one of the main pathogenesis of POTS (Liao et al., 2013). note: 'Found by winnow, kev and lev in p007, p020, p006. Claude judged: supports.' - paper: pmid39768649 cited: true text: full license: by verdict: supports section: 4. Discussion quote: 'In the expert consensus on POTS of the NIH, the authors recognized eight possible mechanisms leading to POTS [2]: hypovolemia, deconditioning, inflammation such as from mast cell activation syndrome (MCAS), excessive central sympathetic activation, auto-antibodies activating cardiac receptors or inhibiting vascular receptors, small fiber neuropathy, and hEDS with connective tissue laxity.' note: 'Found by winnow, kev and lev in p004, p022, p030. Claude judged: supports.' - paper: pmid39582682 cited: true text: full license: by verdict: supports section: Headache disorders in hEDS and HSD > Orthostatic headaches > Postural tachycardia syndrome quote: Other possible causes include a hyperadrenergic state, excessive histamine-induced vasodilation possibly in context of comorbid mast cell activation syndrome, as well as use of vasoactive drugs (e.g., tricyclic antidepressants and opiates) again due to comorbid conditions in hypermobile patients. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid39355826 cited: true text: full license: by verdict: supports section: Discussion quote: Despite similar clinical characteristics, POTS is likely a heterogeneous group of disorders. These include an autoimmune mechanism associated with antibodies to the postsynaptic acetylcholine receptors of the autonomic nerves, high levels of circulating norepinephrine as a result of a genetically determined malfunction of norepinephrine reuptake proteins, and importantly, a form of autonomic cardiac neuropathy. note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid39297132 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Many pathophysiological mechanisms have been proposed, including, but not limited to, inadequate volume regulation (hypovolemic POTS), peripheral noradrenergic denervation (neuropathic POTS), increased sympathetic activity and circulating catecholamines (hyperadrenergic POTS), mast cell activation, and the presence of activating autoantibodies.1 note: 'Found by winnow, kev and lev in p001, p007, p002. Claude judged: supports.' - paper: pmid39268060 cited: true text: full license: by verdict: supports section: Overview of POTS > Proposed mechanisms underlying POTS quote: Several mechanisms have been proposed as the potential pathophysiology behind POTS and are often labeled as the sub-types of neuropathic, hyperadrenergic and hypovolemic POTS (40). note: 'Found by winnow, kev and lev in p035, p033. Claude judged: supports.' - paper: pmid39165715 cited: true text: full license: by-nc verdict: supports section: Highlight key points quote: Many mechanisms have been defined in POTS etiology, such as autonomic denervation, hypovolemia, hyperadrenergic stimulation, low condition, and hypervigilance [4]. note: 'Found by winnow, kev and lev in p007, p001. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p004, p005, p028. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p002, p024, p001. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome quote: POTS is theorized to be the culmination of multiple underlying pathological processes, including peripheral neuropathy/denervation, hypovolemia with altered renin–aldosterone levels, and a hyperadrenergic state. note: 'Found by winnow, kev and lev in p009, p013. Claude judged: supports.' - paper: pmid38336892 cited: true text: full license: by verdict: supports section: Introduction quote: Various POTS etiologies have been hypothesized such as abnormal hyperadrenergic activation due to catecholamine excess, compensatory tachycardia due to peripheral autonomic neuropathy, and chronic autoinflammatory or autoimmune processes5. note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: Pathophysiology of POTS quote: POTS, a syndrome of heterogeneous aetiologies, is linked to deconditioning from prolonged space flight or bed rest, volume dysregulation, mast cell activation disorders, autoimmunity, and hyperadrenergic state.[1–3] Irrespective of aetiology, the exaggerated orthostatic HR response in POTS is associated with three distinct pathophysiological entities, namely peripheral autonomic dysfunction, absolute hypovolaemia, and central hyperadrenergic state (Figure 2). note: 'Found by winnow, kev and lev in p005, p009, p010. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Introduction quote: POTS may be classified into phenotypes—neuropathic, hypovolemic, and hyperadrenergic—based on suspected pathophysiologic mechanism. note: 'Found by winnow, kev and lev in p004, p018. Claude judged: supports.' - paper: pmid37999672 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37999672. Found by winnow, kev and lev in p006, p025, p026. Claude judged: supports.' - paper: pmid37705599 cited: true text: full license: by verdict: supports section: Introduction quote: Other etiologies of POTS include abnormally increased sympathetic activity, excess circulating catecholamines (CAs), and absolute hypovolemia due to low blood volume. note: 'Found by winnow, kev and lev in p005, p023, p025. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 3. Etiopathogenic basis quote: The pathophysiological mechanisms resulting in autonomic dysfunction in POTS may include sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac sympathoexcitation response (hyperadrenergic POTS) with increased serum norepinephrine, volume dysregulation (hypovolemia), baroreceptor dysfunction, peripheral neuropathy, and autoimmunity due to molecular mimicry following infections by pathogens such as Epstein–Barr virus, cytomegalovirus, or Borrelia Burgdorferi (1, 15). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: POTS could result from mild autonomic neuropathy, hypovolemia and abnormal renin-aldosterone response, and genetic or acquired deficiency of norepinephrine receptors leading to a hyperadrenergic state [15]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid37508741 cited: true text: full license: by verdict: supports section: 4. Discussion quote: The main mechanism of POTS is autonomic nerve dysfunction due to increased sympathetic excitation resulting from elevated plasma NE levels [17]. note: 'Found by winnow, kev and lev in p002, p019. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: '4. Individualized Pharmacologic Therapies for Pediatric POTS: Predictors of Therapeutic Efficacy > 4.3. Predictors for Metoprolol Efficacy in Pediatric POTS > 4.3.1. Orthostatic Plasma Norepinephrine Level' quote: Increased sympathetic activity is a main mechanism underlying POTS. The elevation of upright plasma norepinephrine levels may induce impaired vasoconstriction via the baroreceptor reflex [76]. note: 'Found by winnow, kev and lev in p011, p032, p005. Claude judged: supports.' - paper: pmid37378164 cited: true text: full license: by verdict: supports section: Introduction quote: The two significant hypotheses for the pathophysiology can be divided into neuropathic POTS, a form of parasympathetic denervation occurring in the lower extremities, forcing a burst of sympathetic outflow as a corrective effort. It can also be divided into hyperadrenergic POTS, an excessive outburst of norepinephrine when initiating an erect position. note: 'Found by winnow, kev and lev in p003, p006. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: supports section: Pathophysiology of POTS quote: Excessive sympathetic outflow (causing orthostatic hypertension), down-regulated venous receptors (causing decreased venous return), decreased plasma aldosterone-to-renin ratio (causing reduced sodium retention and plasma volume expansion), and elevated angiotensin II without concomitant hypertension (decreased sensitivity to vasoconstrictive effects) are some of the mechanisms that have been identified in the pathophysiology of POTS [13]. Other factors that have been identified as precipitating POTS include hypovolemia, deconditioning, neuroendocrine dysfunction (central hyperadrenergic state), neuropathy, infection, medications (antihypertensives, antipsychotics), surgery, pregnancy, concussion, and autoimmunity [14]. note: 'Found by winnow, kev and lev in p009, p021. Claude judged: supports.' - paper: pmid37209261 cited: true text: full license: none verdict: supports section: Introduction > Mechanisms of Cardiac Damage quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37209261. Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Abstract quote: The exact mechanisms of post-COVID-19 POTS are unclear. Still, different hypotheses have been given, including autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-CoV-2, or sympathetic nervous system stimulation secondary to infection. note: 'Found by winnow, kev and lev in p001, p020. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Discussion quote: A hyperadrenergic state associated with elevated levels of norepinephrine may also lead to the syndrome. note: 'Found by winnow, kev and lev in p003, p014, p015. Claude judged: supports.' - paper: pmid36873318 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Multiple pathophysiologic mechanisms have been proposed to explain POTS, including autonomic neuropathy, hypovolemia, impaired vasoconstriction, and hyperadrenergic state.2,3 note: 'Found by winnow, kev and lev in p007, p021, p024. Claude judged: supports.' - paper: pmid36781629 cited: true text: full license: by verdict: supports section: Discussion quote: In addition, the norepinephrine elimination mechanism is impaired among POTS patients with significant sympathetic activation [28, 29]. Therefore, attention has been given to the role of hyperadrenaline status in developing POTS. note: 'Found by winnow, kev and lev in p034, p006, p035. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: The pathophysiology of POTS remains unknown, however there is a number of physiological mechanisms that have been supposed to be involved. These may include sympathetic dysregulation, hypovolemia, hyperadrenergic stimulation, deconditioning12,57, autoantibody mediated response57, and mast cell activation58,59. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid36292504 cited: true text: full license: by verdict: supports section: 4. Discussion quote: As one of the mechanisms of POTS is excess sympathetic activation (Vernino 2021), we hypothesize that also in milder COVID-19 patients, initially a high sympathetic drive is present, which disappears over time during recovery of the infection. note: 'Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid36187012 cited: true text: full license: by verdict: supports section: Discussion quote: Although the underlying mechanisms for POTS are heterogeneous, excessively increased sympathetic activity is one of the most contributing factors to POTS. note: 'Found by winnow, kev and lev in p022, p006. Claude judged: supports.' - paper: pmid36111700 cited: true text: full license: by-nc verdict: supports section: Introduction quote: The precise aetiology of POTS remains unknown, although the haemodynamic changes are thought to reflect convergence of multiple pathophysiological processes including peripheral autonomic neuropathy, hypovolemia, elevated sympathetic tone, deconditioning and auto‐antibodies to cardiovascular receptors [7]. note: 'Found by winnow, kev and lev in p027, p005, p006. Claude judged: supports.' - paper: pmid36000360 cited: true text: full license: by verdict: supports section: Discussion > POTS phenotypes quote: Hyperadrenergic POTS is believed to result from increased levels of circulating norepinephrine, while patients with neuropathic POTS have partial neuropathy in lower vascular beds. note: 'Found by winnow, kev and lev in p065, p079, p049. Claude judged: supports.' - paper: pmid35992935 cited: true text: full license: by verdict: supports section: Introduction quote: Other proposed pathophysiological mechanisms include abnormally increased sympathetic activity and circulating catecholamine excess (hyperadrenergic type; Schondorf and Low, 1993; Jacob and Biaggioni, 1999), and absolute hypovolemia due to low blood volume (Vernino et al., 2021). note: 'Found by winnow, kev and lev in p005, p025, p004. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p017, p005, p009. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.4. Physiological Predictors for the Efficacy of Metoprolol in Pediatric POTS quote: A hyperadrenergic state is one of the important mechanisms leading to POTS. Increases in orthostatic plasma norepinephrine, which might be the result of damaged baroreflex-mediated vasoconstriction, represent the key hyperadrenergic biochemical change in patients with POTS [83]. note: 'Found by winnow, kev and lev in p040, p003, p010. Claude judged: supports.' - paper: pmid35733987 cited: true text: full license: by verdict: supports section: Introduction quote: The etiology is not fully understood, elevated circulating norepinephrine levels have been reported in POTS patients suggesting that increased sympathetic activity may play a role (Goldstein et al., 2002; Lambert et al., 2008). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid35351159 cited: true text: full license: by verdict: supports section: Discussion > Comorbidities of patients with PF quote: Enhanced sympathetic response has been proposed as a mechanism of POTS among patients with PF. note: 'Found by winnow, kev and lev in p004, p016. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What is the pathophysiology of POTS? quote: Features described in subgroups of patients include increased sympathetic nervous system tone (i.e., hyperadrenergic POTS),17 partial peripheral sympathetic denervation leading to relative central hypovolemia (i.e., neuropathic POTS)27 and low blood volume (i.e., absolute hypovolemia),28 which may drive some of the other hemodynamic findings. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid35232225 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35232225. Found by winnow, kev and lev in p007, p022, p031. Claude judged: supports.' - paper: pmid35127870 cited: true text: full license: by verdict: supports section: Introduction quote: Its main pathogenesis includes high catecholamine levels in blood circulation, overexcitement of sympathetic nerve function, vasodilation, or low central blood volume (3–6). note: 'Found by winnow, kev and lev in p034, p005, p035. Claude judged: supports.' - paper: pmid35118574 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35118574. Found by winnow, kev and lev in p006, p027, p029. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mechanisms quote: Hyperadrenergic stimulation in POTS is thought to be genetic. This manifestation affects up to 50% of patients with POTS and is considered to involve a centrally driven sympathetic activation characterized by supine vasoconstriction and tachycardia.5,8,14,15 note: 'Found by winnow, kev and lev in p018, p013. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Putative Mechanisms for Symptomatic Tachycardia in Post-COVID-19 Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Introduction > Definition of postural orthostatic tachycardia syndrome quote: The onset of POTS has been attributed to dysautonomia, hypovolemia, deconditioning, a hyperadrenergic physiologic state, hypervigilance (unusual focus on bodily sensations), or any combination of these conditions.1 note: 'Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p014, p023, p024. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: ANS in the CNS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026, p006, p024. Claude judged: supports.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Potential causes of excessive sympathetic activation in POTS include absolute or positional central hypovolemia,5 intrinsically increased sympathetic CNS outflow as proposed in hyperadrenergic POTS, or increased central command in the face of postural muscle atrophy.48 note: 'Found by winnow, kev and lev in p055, p006, p051. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Introduction quote: Hyperadrenergic POTS is due to an excess sympathetic response. note: 'Found by winnow, kev and lev in p006, p007, p023. Claude judged: supports.' - paper: pmid33150760 cited: true text: full license: by verdict: supports section: Body quote: However, it seems that there are two main types of POTS, the adrenergic and neuropathic type (10). The adrenergic type is characterized by high plasma norepinephrine (NE) levels due to NE synaptic spillover, with values in the upright position exceeding 3.5 nmol/L. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots quote: Current perspectives on the pathogenesis of POTS have been categorized as altered central blood volume, abnormal autonomic reflexes and elevated sympathetic tone, damaged skeletal muscle pump activity, local vascular tension regulation dysfunction, iron insufficiency, mast cell activation (MCA), and autoimmune dysfunction (3, 6, 12). note: 'Found by winnow, kev and lev in p007, p011, p012. Claude judged: supports.' - paper: pmid32848537 cited: true text: full license: by verdict: supports section: Introduction quote: The cause of POTS has not yet been established (Benarroch, 2012), though many possible disease mechanisms including autonomic denervation (Kimpinski et al., 2012; Haensch et al., 2014), autonomic autoimmunity (Ruzieh et al., 2017), hypovolemia (Benarroch, 2012; Kimpinski et al., 2012), hyperadrenergic stimulation (Kimpinski et al., 2012), and deconditioning have been proposed (Benarroch, 2012; Fu and Levine, 2015). note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid32823577 cited: true text: full license: by verdict: supports section: 1. Introduction quote: The pathophysiology of POTS is poorly understood [1,2]. Proposed mechanisms include neuropathic and hyperadrenergic dysregulation, volume depletion, physical deconditioning, and autoimmunity [14,15,16,17,18]. note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Several potential underlying mechanisms have been suggested for POTS including autonomic denervation, hypovolemia, hyperadrenergic stimulation, and autoantibodies against adrenergic receptors. note: 'Found by winnow, kev and lev in p017, p031. Claude judged: supports.' - paper: pmid32743496 cited: true text: full license: by verdict: supports section: Introduction quote: The pathophysiology of POTS is not well understood, and is thought to reflect the integration of multiple pathophysiological processes, including autoimmune, hyperadrenergic, and hypovolemic mechanisms [3]. note: 'Found by winnow, kev and lev in p006, p032, p035. Claude judged: supports.' - paper: pmid32673517 cited: true text: full license: by-nc verdict: supports section: Body quote: POTS is a heterogeneous condition associated with multiple pathophysiological mechanisms. In some patients, the orthostatic tachycardia is thought to be caused by a primary sympathetic activation, whereas in others it is thought to be secondary to chronic hypovolemia, partial sympathetic denervation in lower limbs, cardiovascular deconditioning, mast cell activation, or autoimmunity.7, 8, 9, 10, 11, 12 note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid32612820 cited: true text: full license: by verdict: supports section: Introduction quote: The pathophysiology remains unknown but many theories have been described including hypovolemia, autonomic dysfunction, hyperadrenergic state, adrenergic receptor deficiency, mast cell activation, renin-aldosterone paradox and physical deconditioning [10]. This may explain why various treatment options have been used for the management of POTS, but with suboptimal results. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Mechanisms and symptoms quote: As noted by Ziffra et al.,1 although not completely understood, the pathophysiology of postural orthostatic tachycardia syndrome (POTS) appears to be multifactorial. Autonomic nervous system dysfunction,2 increased sympathetic tone,3 and physical deconditioning4,5 are some of the suggested contributory factors. note: 'Found by winnow, kev and lev in p001, p011, p019. Claude judged: supports.' - paper: pmid32222376 cited: true text: full license: none verdict: supports section: Etiology and the concepts of primary and secondary POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32222376. Found by winnow, kev and lev in p003, p020, p021. Claude judged: supports.' - paper: pmid31888497 cited: true text: full license: by verdict: supports section: Background quote: Sympathetic denervation in lower extremities, preserved cardiac innervation and increased sympathetic activities (hyper-adrenergic state) have been shown to be sole etiologies of POTS [2, 3, 6, 8]. note: 'Found by winnow, kev and lev in p008, p046. Claude judged: supports.' - paper: pmid31798399 cited: true text: full license: by verdict: supports section: Introduction > Orthostatic Cardiovascular Responses Are Impaired in Patients With Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: 'Postural Orthostatic Tachycardia Syndrome includes at least four subtypes: hyperadrenergic POTS with excessive sympathetic discharge; hypovolemic POTS (with compensatory tachycardia); neuropathic POTS with impaired vasoconstriction and compensatory tachycardia; and, rarely, noradrenaline transporter deficiency with synaptic noradrenaline accumulation (Low et al., 1995, 2009; Raj, 2013).' note: 'Found by winnow, kev and lev in p053, p011, p013. Claude judged: supports.' - paper: pmid31788462 cited: true text: full license: by verdict: supports section: Discussion quote: The role of hyper-adrenergic state in the development of POTS has gained more and more attention in recent years. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid31547749 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: From a pathological viewpoint, an α1AR‐AAb‐mediated impaired pressor response to α1AR endogenous ligand norepinephrine would be expected to compensatorily increase the sympathetic output to normalize vasoconstriction and blood pressure. The relatively unprotected cardiac chronotropic β1AR would respond to this increased adrenergic activity with an enhanced tachycardia, which would be exaggerated by the β1AR‐AAb, and might explain the clinical characteristics of POTS. note: 'Found by winnow, kev and lev in p003, p023, p005. Claude judged: supports.' - paper: pmid31384930 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Several potential underlying mechanisms have been suggested for POTS including autonomic denervation, hypovolaemia, hyperadrenergic stimulation, and autoantibodies against adrenergic receptors.2,3 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid31307619 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31307619. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid31156539 cited: true text: full license: by verdict: supports section: Discussion quote: Cardiovascular autoantibodies with a causative role have been proposed in POTS, but another hypothesis is the presence of abnormally increased sympathetic activity alongside findings of peripheral autonomic neuropathy. note: 'Found by winnow, kev and lev in p038, p007. Claude judged: supports.' - paper: pmid30372565 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30372565. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Clinical approach toward POTS diagnosis > Investigations > Plasma and urine catecholamines quote: Hyperadrenergic POTS may relate to an increase in production of norepinephrine37 or defective norepinephrine clearance.38–42 note: 'Found by winnow, kev and lev in p015, p003, p016. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid27660311 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27660311. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: 'Abstract > Conclusions:' quote: The pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. note: 'Found by winnow, kev and lev in p004, p010, p005. Claude judged: supports.' - paper: pmid26610893 cited: true text: full license: by-nc verdict: supports section: INTRODUCTION quote: The pathophysiological mechanisms underlying POTS are also diverse and multifactorial, and include hypovolemia,5 hyperadrenergic states,6 lower-extremity neuropathies,7 and deconditioning.8 note: 'Found by winnow, kev and lev in p005, p011. Claude judged: supports.' - paper: pmid26241226 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: Other possible causes of POTS are a central hyperadrenergic state, which has a genetic predisposition, and indolent mastocytosis.7–14 note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p023, p026, p027. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Physiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p011, p014, p025. Claude judged: supports.' - paper: pmid25811760 cited: true text: full license: by verdict: supports section: Discussion quote: The increased plasma level of catecholamine was suggested to be involved in the pathogenesis of POTS [18,19], evidenced by a heart rate increment in such children. note: 'Found by winnow, kev and lev in p021, p018, p019. Claude judged: supports.' - paper: pmid25792354 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25792354. Found by winnow, kev and lev in p004, p017. Claude judged: supports.' - paper: pmid25483980 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p005, p020. Claude judged: supports.' - paper: pmid25204388 cited: true text: full license: by verdict: supports section: Discussion quote: It is known that hyperadrenergic state has been well recognized one of the important mechanisms for POTS, and present study firstly provided the information about the role of plasma norepinephrine as a biomarker to predict the effect of treatment of metoprolol on POTS children. note: 'Found by winnow, kev and lev in p022, p012. Claude judged: supports.' - paper: pmid25180969 cited: true text: full license: by verdict: supports section: Discussion quote: Various hypotheses, such as hypovolemia [37], venous pooling [38], hyperadrenergic states [39]–[41], and restricted adrenergic neuropathies [42] have been suggested to be possible mechanisms underlying POTS. note: 'Found by winnow, kev and lev in p002, p022. Claude judged: supports.' - paper: pmid25120493 cited: true text: full license: by verdict: supports section: Conclusion quote: POTS on the other hand may involve sympathetic denervation in the lower limbs, a hyperadrenergic state and/or abnormalities in the NET. note: 'Found by winnow, kev and lev in p017, p019, p020. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: Abstract quote: Some patients with POTS have evidence of elevated sympathoneural tone. This hyperadrenergic state is likely a driver of the excessive orthostatic tachycardia. note: 'Found by winnow, kev and lev in p001, p004, p020. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p045, p048, p070. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p003, p026. Claude judged: supports.' - paper: pmid24002370 cited: true text: full license: by-nc verdict: supports section: Discussion > Norepinephrine and POTS quote: 'Despite the heterogeneous pathophysiology of POTS, increased sympathetic activity seems to be a common final pathway, and thus an area of focus in POTS research. There are two possible mechanisms for increased synaptic concentrations of norepinephrine: an increase in synaptic norepinephrine release or a decrease in synaptic norepinephrine clearance.' note: 'Found by winnow, kev and lev in p030, p031, p032. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Pathogenesis of POTS is heterogenous and may include sympathetic hyperactivity with peripheral denervation, hypovolemia, and physical deconditioning [3]. note: 'Found by winnow, kev and lev in p009, p006, p008. Claude judged: supports.' - paper: pmid23720636 cited: true text: full license: by verdict: supports section: Cognitive impairment theories > Neurotransmitters in CFS and POTS quote: Shannon et al. (2000) found that in the case of one family, the cause of POTS was traced to a point mutation in the coding region of the NET gene which produced a dysfunctional transporter protein. This defect was found to augment the sympathoneural signal, and also increased the rate of overflow of norepinephrine into plasma. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid23283362 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23283362. Found by winnow, kev and lev in p006, p007. Claude judged: supports.' - paper: pmid23244360 cited: true text: full license: none verdict: supports section: 'Common variant OI: POTS & postural VVS > Hyperadrenergic POTS' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23244360. Found by winnow, kev and lev in p020, p021, p017. Claude judged: supports.' - paper: pmid21977261 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p007, p016. Claude judged: supports.' - paper: pmid21906029 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: The orthostatic tachycardia in POTS is easily explained by this increase in sympathetic activity and the corresponding decrease in vagal tone evidenced by the decrease in high frequency power spectra of HR. note: 'Found by winnow, kev and lev in p029, p033. Claude judged: supports.' - paper: pmid21266211 cited: true text: full license: none verdict: supports section: Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21266211. Found by winnow, kev and lev in p030, p004, p007. Claude judged: supports.' - paper: pmid19289653 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19289653. Found by winnow, kev and lev in p002, p039. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p001, p003, p004. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: There are some cases, however, in which the primary underlying problem seems to be excessive sympathetic discharge. These patients often have extremely high levels of upright norepinephrine. note: 'Found by winnow, kev and lev in p028, p024, p031. Claude judged: supports.' - paper: pmid12416949 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 12416949. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid11458707 cited: true text: abstract license: none verdict: supports section: Abstract > Unlabelled quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11458707. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid11201632 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11201632. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid9868411 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 9868411. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Introduction and background quote: The research does not support the notion that a single mechanism is responsible for the development of cognitive symptoms, since POTS is a diverse syndrome with possible hypovolemic, neuropathic, hyperadrenergic, autoimmune, and post-viral subtypes. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid42369281 cited: true text: full license: by verdict: partial section: Toward a trauma-informed conceptual model of POTS quote: Via the PAG, trauma may set the central autonomic network into one of its escape modes, such as fight, flight or freeze; failure to fully recalibrate the autonomic network back to a healthy operating mode after the trauma has passed may contribute to a state of persistent sympathetic activation for predisposed individuals, in turn leading to a dysregulated brain–body communication system that leads to manifestations of ANS dysregulation that increase the risk of a POTS diagnosis. note: 'Found by winnow, kev and lev in p011, p020, p035. Claude judged: partial.' - paper: pmid42037960 cited: true text: full license: by verdict: partial section: Introduction quote: It was noted as a potentially characteristic sign of hyperadrenergic/low-flow subtypes of POTS, which is characterized by excessive sympathetic activation, whereas the low-flow subtype involves impaired peripheral vasoconstriction and reduced venous return; both mechanisms may predispose to transient cutaneous hyperemia during autonomic fluctuations. note: 'Found by winnow, kev and lev in p016, p005. Claude judged: partial.' - paper: pmid41976810 cited: true text: full license: by verdict: partial section: 1. Introduction quote: 'Sheldon et al. [6] summarise two possible mechanisms for PoTS: firstly, autonomic denervation leading to impaired peripheral venoconstriction, which leads to venous pooling, hypovolaemia, and hyperadrenergic stimulation with raised plasma norepinephrine levels, or, secondly, deconditioning, which may be compounded by anxiety and hypervigilance secondary to the underlying physiological abnormalities.' note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid41357159 cited: true text: full license: none verdict: partial section: Discussion > Cardiovascular determinants quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p009, p032, p039. Claude judged: partial.' - paper: pmid40310095 cited: true text: full license: by verdict: partial section: 4. Discussion quote: In addition, many patients with POTS also have a primary hyperadrenergic state, and the sympathetic tone is markedly increased, and even more when standing [40,41], which can cause a marked increase in heart rate [42], and as a result, their discomfort is more pronounced when they are upright. note: 'Found by winnow, kev and lev in p035, p036. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Migraine Headaches quote: Post-ganglionic sympathetic denervation and amplified sympatho– adrenomedullary axis activity are felt to be related to the pathophysiology of neurogenic and hyperadrenergic POTS, respectively. note: 'Found by winnow, kev and lev in p016, p034, p024. Claude judged: partial.' - paper: pmid39540412 cited: true text: full license: by-nc verdict: partial section: How to Explain the Pathophysiology to Patients and Families quote: Anxiety about these symptoms potentiates the pathophysiology, as additional excessive adrenaline is made in response—drying out the patient, increasing fluid requirements, and cycling the pathophysiology. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid39463038 cited: true text: full license: by verdict: partial section: DISCUSSION quote: Norcliffe‐Kaufman et al. recently reported that patients with POTS have increased somatic vigilance and may experience an anxiety‐related hyperadrenergic state in an upright position [31], which can trigger hyperventilation and potentially affect cerebral perfusion. The increased sympathetic activity in POTS may therefore be exacerbated by a state of heightened anxiety, which could further increase symptoms. note: 'Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid39395208 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: Although the A457P model failed to result in the recovery of mature NET when co‐expressed with DHHC1, the hypothesis of disordered NET palmitoylation being involved in the pathogenesis of autonomic disorders like POTS remains relevant. Indeed, inhibition of this process strongly decreases surface and total NET protein, thus impairing the cellular uptake of NE and potentially generating a hyperadrenergic state that mimics the cellular and physiologic POTS phenotype. note: 'Found by winnow, kev and lev in p001, p092, p054. Claude judged: partial.' - paper: pmid39297140 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: While upright, patients can also experience exaggerated sympathetic nervous system activity, paralleled by exaggerated increases in ventilation,5, 6, 7, 8, 9 which decreases carbon dioxide levels in the blood (ie, hypocapnia). note: 'Found by winnow, kev and lev in p006, p003. Claude judged: partial.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: Abstract quote: The underlying causes of POTS following COVID-19 remain unknown, with various theories proposed such as renin–angiotensin–aldosterone system (RAAS) dysregulation, hyperadrenergic reaction, and direct viral infection. note: 'Found by winnow, kev and lev in p001, p007, p008. Claude judged: partial.' - paper: pmid39076856 cited: true text: full license: by verdict: partial section: 5. Symptoms and Pathologic Findings of Cardiovascular Disease in Post-Acute COVID-19 Syndrome > 5.2 Pathologic Findings > 5.2.4 Postural Orthostatic Tachycardia Syndrome (POTS) quote: "Hypothetically, POTS is caused by autonomic dysfunction in long COVID patients \n[138]. Autonomic dysfunction\ \ in long COVID is provoked by the hyperadrenergic \nstate and the resetting of baroreceptor control, which\ \ is stimulated by \nangiotensin II upregulation." note: 'Found by winnow, kev and lev in p043. Claude judged: partial.' - paper: pmid38962840 cited: true text: full license: by-nc-nd verdict: partial section: INTRODUCTION quote: The increased baroreceptor activity results in an exaggerated sympathoneural response, resulting in compensatory reflex tachycardia [8, 10]. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid38585862 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38585862. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: partial section: DISCUSSION quote: Malfunction of these nuclei could give rise to sympathetic hyperactivity, producing HR and SBP disturbances during postural changes, as could be seen in hyperadrenergic POTS [7]. note: 'Found by winnow, kev and lev in p006, p018, p020. Claude judged: partial.' - paper: pmid37631004 cited: true text: full license: by verdict: partial section: 8. Electroceutical Therapy for Autoimmune Disease > 8.7. Postural Orthostatic Tachycardia Syndrome (POTS) quote: Consistently, induction of antibodies with similar functional properties in a rabbit experimental model could trigger a hyperadrenergic POTS phenotype [94]. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid37435242 cited: true text: full license: by verdict: partial section: Discussion quote: Some patients have shown evidence of increased adrenergic function separate from tachycardia, suggesting that POTS represents a hyperadrenergic state. Commonly, patients with POTS have increased catecholamine levels than healthy controls [8]. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Discussion quote: Additionally, the role of angiotensin-converting enzyme 2 (ACE2) receptor dysfunction has been implicated in the etiology of POTS, as COVID-19 attenuates ACE2 receptor activity and consequently upregulates sympathetic activation [14]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid36818521 cited: true text: full license: by-nc-nd verdict: partial section: Discussion > Possible Mechanisms for OI and Role of the Autonomic Nervous System quote: Many factors, such as hypovolemia, an excessive orthostatic shift in plasma volume, autonomic dysfunction, increased sympathetic tone, physical deconditioning, poor venous return, enhanced blood venous pooling, and immunological factors, may contribute to the occurrence of OI with POTS.24 note: 'Found by winnow, kev and lev in p005, p021. Claude judged: partial.' - paper: pmid36414707 cited: true text: full license: by verdict: partial section: Abstract quote: These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder. note: 'Found by winnow, kev and lev in p027, p030, p001. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Management: Pharmacologic Treatment > Postural Orthostatic Tachycardia Syndrome49,50,170' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p035, p158, p166. Claude judged: partial.' - paper: pmid35802513 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35802513. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34746821 cited: true text: full license: by-nc-nd verdict: partial section: Introduction > Carotid body – a unifying hypothesis? quote: This predisposes patients to hypoperfusion of tissues cephalad to the heart, causing stagnant hypoxia from reduced carotid blood flow – a key step causing SNA activation (Marshall, 1994; Prabhakar et al., 2005) in the pathophysiologic cascade in POTS. note: 'Found by winnow, kev and lev in p001, p010, p011. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Discussion quote: It is postulated that the cytokine storm from the COVID-19 infection results in sympathetic dysregulation, causing the abnormal autonomic response in POTS [6]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid34634682 cited: true text: full license: none verdict: partial section: Introduction > Postural Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34634682. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid34409582 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34409582. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid34268642 cited: true text: full license: none verdict: partial section: Autonomic Disorders and Headache quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34268642. Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid34055686 cited: true text: full license: by verdict: partial section: Discussion quote: The exaggerated response to adrenergic receptors, the increased catecholamine levels, and the exacerbated hypovolemic state in the morning may explain the excessive HR increment after standing observed in the morning for POTS children and adolescents. note: 'Found by winnow, kev and lev in p025, p027. Claude judged: partial.' - paper: pmid34035985 cited: true text: full license: by verdict: partial section: Discussion quote: Hyperadrenergic states, usually the result of a genetic predisposition, can lead to increased norepinephrine (NE) levels which, together with impaired clearance or decreased uptake, can manifest as anxiety, tremulousness, and elevated diastolic BP.5 note: 'Found by winnow, kev and lev in p008, p011. Claude judged: partial.' - paper: pmid33926653 cited: true text: full license: none verdict: partial section: DISCUSSION > Sodium Loading in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p009, p043, p048. Claude judged: partial.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: These antibodies exerted a partial antagonistic effect against the peripheral vasoconstrictive compensation of orthostasis, resulting in an overshooting sympathoneural response to maintain vascular tone. Consequently, this sympathetic response leads to tachycardia via unopposed β1-adrenergic receptor activation. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Introduction quote: The multiple factors like moderate autonomic dysfunction, increased sympathetic tone, inadequate venous return or excessive blood venous pooling, and severe deconditioning may be responsible for POTS symptoms. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid33486983 cited: true text: full license: none verdict: partial section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33486983. Found by winnow, kev and lev in p003, p017, p022. Claude judged: partial.' - paper: pmid33316414 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid33114659 cited: true text: full license: by verdict: partial section: 1. Introduction quote: 'The pathophysiological mechanisms of POTS remain poorly understood and three different phenotypes are described: the “hyper-adrenergic” [3], the “neuropathic” [6,7,8] and POTS associated with physical deconditioning [4,9,10] or to a prolonged exposure to gravity absence [4,11,12,13].' note: 'Found by winnow, kev and lev in p005, p050, p003. Claude judged: partial.' - paper: pmid32880754 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p006, p008. Claude judged: partial.' - paper: pmid32284866 cited: true text: full license: by-nc verdict: partial section: Discussion quote: 'The aetiology of POTS is uncertain, but a number of mechanisms have been proposed. Increased sympathetic activity appears to be a common feature.' note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid31780890 cited: true text: full license: by verdict: partial section: Discussion quote: Previous studies suggested that metoprolol could achieve better therapeutic effects in children with high catecholamine level, high adrenergic status, and β-receptor hypersensitivity (Thieben et al., 2007). note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p031. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: PATHOPHYSIOLOGY OF POTS quote: The excessive sympathetic tone is considered to be of central origin in hyperadrenergic POTS, but smaller increases in plasma NE upon standing, which are not uncommon in POTS, may also result as a compensatory response to hypovolemia and peripheral autonomic neuropathy. In some patients with POTS, a deficiency in the NE transporter protein may also lead to an excessive NE response.43,44 note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.2 Hyperadrenergic State quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p017, p018, p022. Claude judged: partial.' - paper: pmid27938459 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27938459. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid25713509 cited: true text: full license: by verdict: partial section: Neurovisceral phenotypes > Joint hypermobility > Association with psychiatric disorder quote: In disorders that typically involve impaired collagen (present in blood vessels) such as joint hypermobility and postural tachycardia syndrome it is likely that reduced venous return during standing due to venous pooling or denervation causing low plasma volume may be responsible for a an increased sympathetic state–as the body attempts to compensate for these abnormalities—resulting in orthostatic intolerance and associated symptoms (Bohora, 2010; Benarroch, 2012; Mathias et al., 2012). note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid25653673 cited: true text: full license: by verdict: partial section: Discussion quote: Among other mechanisms are the vagal impairment and hyperadrenergic activity supported by the high levels of upright plasma epinephrine (reflecting SNS activation) in this study and marked impairment of cardiac baroreflex sensitivity (23-25). Furthermore, compensatory increase in cerebral sympathetic outflow leads to elevated norepinephrine levels, which result in an increase in HR and myocardial contractility (19, 26). note: 'Found by winnow, kev and lev in p024, p025. Claude judged: partial.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: partial section: Abstract > Conclusions quote: POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients. note: 'Found by winnow, kev and lev in p003, p006, p026. Claude judged: partial.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: partial section: Pathophysiology quote: Muenter swift et al.[19] showed POTS patients have exaggerated muscle sympathetic nerve activity (MSNA) responses to baroreflex challenges compared to healthy control subjects, although resting supine MSNA values did not differ between the groups. note: 'Found by winnow, kev and lev in p014, p012, p013. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p035, p009. Claude judged: partial.' - paper: pmid21751966 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21751966. Found by winnow, kev and lev in p002, p020. Claude judged: partial.' - paper: pmid19324216 cited: true text: full license: none verdict: partial section: WHY ARE “POSITIVE” TILT TEST RESULTS SIMILAR (EARLY ON) IN FAINTERS AND POTS? quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19324216. Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid17709712 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 17709712. Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid11206727 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11206727. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid11198483 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11198483. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - autoimmune_evidence - proposed_mechanism_of - pots papers: 136 evidence: - paper: pmid42688561 cited: true text: full license: by-nc verdict: supports section: Discussion > Pathophysiological Mechanisms of POTSHR quote: Several mechanisms have been proposed for POTS in COVID-19 survivors, including autoimmunity, autonomic neuropathy, hypovolaemia, deconditioning and persistent inflammation, among which autoimmunity is prominent, where autoantibodies form against A/B adrenoceptors and muscarinic acetylcholine receptors. note: 'Found by winnow, kev and lev in p034. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: Research is underway to establish a link between certain autoantibodies, such as G-protein-coupled adrenergic receptors and muscarinic cholinergic receptor antibodies found in elevated levels in POTS, which corresponds to the theory that POTS may have an immune-mediated pathogenesis [19]. note: 'Found by winnow, kev and lev in p084. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Discussion quote: Besides small fiber neuropathy, proposed POTS mechanisms include immune-mediated inflammation triggered by autoantigens or persistent viral particles [11, 20]. note: 'Found by winnow, kev and lev in p047. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Autoimmunity > Autoimmune markers in POTS and other common autonomic disorders quote: The pathophysiology of POTS has been deemed largely heterogeneous and traditionally classified as neuropathic, hypovolemic, and hyperadrenergic (Low et al., 2009). In the past decade, however, investigators zeroed in on autoimmunity as one of the major mechanisms. note: 'Found by winnow, kev and lev in p003, p014, p018. Claude judged: supports.' - paper: pmid41069916 cited: true text: full license: by verdict: supports section: Editorial quote: Although the pathophysiology of POTS remains complex and not fully understood, several studies suggest the possibility of an immunological cause in a significant portion of the cases [1,3,5,6,10], which might be triggered by stressors such as viral infections, trauma, pregnancy, or surgery [3]. Immune dysfunction caused by the aforementioned factors might lead to the formation of autoantibodies against adrenergic, cholinergic, and acetylcholine receptors [5], henceforth paving the way to autoimmunity. note: 'Found by winnow, kev and lev in p004, p001, p002. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 4 Discussion quote: Hypotheses regarding pathophysiology include abnormally increased sympathetic activity, sympathetic denervation leading to hypovolemia and reflex tachycardia, and autoimmunity to G-protein coupled receptors (2, 3, 79, 81, 82). note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid40776616 cited: true text: full license: by-nc verdict: supports section: Discussion quote: It is caused by a complex interaction of cardiac receptor-activating autoantibodies, hyperadrenergic activation, hypovolemia, and partial autonomic neuropathy [8,24-26], with impairment of cerebrovascular autoregulation being an important pathogenic mechanism. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid40763323 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Increased viral exposure may have triggered autoimmune mechanisms that contribute to the pathogenesis of POTS. Autoantibodies targeting adrenergic and muscarinic receptors are known to play a role in POTS, and viral infections have been shown to stimulate the production of such autoantibodies.6-9 note: 'Found by winnow, kev and lev in p024, p006, p028. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Introduction quote: The precise pathophysiology of POTS is not fully understood but several factors may contribute, including hyperadrenergic stimulation, hypovolemia, peripheral autonomic neuropathy, and autoimmunity.6 note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Given the proposed role of modulatory autoantibodies targeting ARs in POTS, we also conducted a post hoc analysis to measure AR-modulating autoantibody activity in patients with and without POTS.28,29 note: 'Found by winnow, kev and lev in p004, p010, p032. Claude judged: supports.' - paper: pmid40432440 cited: true text: full license: by verdict: supports section: Introduction quote: In 2012, Wang et al. were the first to imply autoimmunity as a possible etiology of POTS by detecting autoimmune IgG antibodies in patients with POTS [9]. Later, in 2014, Li et al. documented specific antibodies against receptors in the autonomic nervous system in POTS patients, specifically autoantibodies against adrenergic alpha-1 receptors (ADRA1) and autoantibodies against beta-1 (ADRB1) and beta-2 adrenergic receptors (ADRB2) [10]. note: 'Found by winnow, kev and lev in p001, p007, p008. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 2. Case Presentation quote: However, an autoimmune basis of post-COVID POTS was evident given a positive ANA, comorbid SFN, and post-infectious onset of symptomatology. It was previously demonstrated pre-COVID-19 pandemic that patients with POTS have a higher prevalence of positive ANA and other autoimmune markers than the general population [5]. note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid39597891 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Other etiologies of POTS have been implicated more recently, including autoimmunity and possible neuroinflammation [10,11]. note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Patients with autoimmune-related POTS may also present with autoimmune disorders as comorbidities. The onset of POTS in these patients may be related to autoantibodies against ganglionic acetylcholine receptors and α1-adrenergic receptors, although no definitive pathways have been identified.[10] note: 'Found by winnow, kev and lev in p011, p032, p027. Claude judged: supports.' - paper: pmid39355826 cited: true text: full license: by verdict: supports section: Discussion quote: Despite similar clinical characteristics, POTS is likely a heterogeneous group of disorders. These include an autoimmune mechanism associated with antibodies to the postsynaptic acetylcholine receptors of the autonomic nerves, high levels of circulating norepinephrine as a result of a genetically determined malfunction of norepinephrine reuptake proteins, and importantly, a form of autonomic cardiac neuropathy. note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 2. COVID-19-Related POTS > 2.2. Presumed Mechanism for COVID-19-Related POTS > 2.2.2. Hyperadrenergic Reaction quote: Increased AR antibodies due to COVID-19 infection may lead to vasoconstriction and tachycardia, which has been proposed as a possible mechanism in POTS [35]. note: 'Found by winnow, kev and lev in p014, p027, p009. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: 'Autoimmune: Autoimmune responses directed at components of the ANS or other self-antigens may contribute to the development and progression of POTS, creating an immunological enigma within the etiological framework [40,41].' note: 'Found by winnow, kev and lev in p014, p020, p003. Claude judged: supports.' - paper: pmid38900132 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38900132. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid38736760 cited: true text: full license: by verdict: supports section: Discussion quote: The antibodies that recognize the adrenergic and cholinergic receptors can be considered probably responsible for some alterations presented by the patient, namely dysautonomia symptoms and POTS. This hypothesis is supported by the fact that most patients with POTS possessed autoantibodies that activated ADRA1, ADRB1, and ADRB2 receptors [21]. note: 'Found by winnow, kev and lev in p001, p019, p020. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.1. Adrenergic Receptors quote: The autoantibody-mediated vasodilation mechanism of POTS is apparent when an individual stands. The augmented sympathetic activity leads to orthostatic tachycardia and palpitations. note: 'Found by winnow, kev and lev in p013, p015, p021. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Autoimmunity has been proposed as a possible etiological mechanism in POTS, with high prevalence of diverse antibodies in previous reports (Fedorowski, 2019). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid38240001 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Particularly, the production of adrenergic autoantibodies is believed to be an important factor in postinfection POTS. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010, p018, p009. Claude judged: supports.' - paper: pmid37999672 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37999672. Found by winnow, kev and lev in p025, p005, p006. Claude judged: supports.' - paper: pmid37981644 cited: true text: full license: by verdict: supports section: Discussion quote: We speculate that since acute COVID-19 is known to trigger a profound autoimmune response37,38 and there is evidence of autoimmunity being a potential disease mechanism in classical POTS39,40, autoimmune factors may be decisive for POTS development in PACS. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid37822957 cited: true text: full license: by verdict: supports section: Introduction quote: The exact etiology of POTS is still unknown, although in recent years evidence has accumulated that in a subset of patients with POTS the pathogenesis of dysautonomia may be immune-mediated. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 3. Etiopathogenic basis quote: The pathophysiological mechanisms resulting in autonomic dysfunction in POTS may include sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac sympathoexcitation response (hyperadrenergic POTS) with increased serum norepinephrine, volume dysregulation (hypovolemia), baroreceptor dysfunction, peripheral neuropathy, and autoimmunity due to molecular mimicry following infections by pathogens such as Epstein–Barr virus, cytomegalovirus, or Borrelia Burgdorferi (1, 15). note: 'Found by winnow, kev and lev in p008, p006, p020. Claude judged: supports.' - paper: pmid37631004 cited: true text: full license: by verdict: supports section: 8. Electroceutical Therapy for Autoimmune Disease > 8.7. Postural Orthostatic Tachycardia Syndrome (POTS) quote: Its origin remains under investigation, and a number of underlying physiopathological mechanisms have been proposed, including autoimmune reactions [92]. In support of autoimmune-mediated pathways in POTS is the identification in a subgroup of patients expressing serum antiadrenergic autoantibodies capable of exerting direct agonist and allosteric effects that alter receptor function [93]. note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: Some patients with POTS have an increased association with autoimmune disorders, suggesting immune-mediated pathophysiology of the autonomic nervous system [16]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid37510775 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Pathophysiological mechanisms underlying this phenomenon are unclear though it is believed that autoimmunity may play a crucial role through inappropriate activation of adrenergic and angiotensin receptors [15,16,17,18]. note: 'Found by winnow, kev and lev in p004, p016. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: 3. Main Pathogenesis of POTS quote: Based on these findings, autoimmune dysfunction is considered one of the pathogenic mechanisms responsible for POTS. note: 'Found by winnow, kev and lev in p013, p008. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: An autoimmune basis for a small number of POTS patients has been linked to the observation of orthostatic symptoms following a viral illness [11]. Additionally, autoantibodies to the ganglionic nicotinic acetylcholine receptor and alpha 1 adrenergic, beta 1 and 2 adrenergic, and angiotensin II type 1 receptors have been detected in a few patients. note: 'Found by winnow, kev and lev in p005, p006, p001. Claude judged: supports.' - paper: pmid37393658 cited: true text: full license: none verdict: supports section: DISCUSSION > RAAS Abnormalities in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: POTS and COVID-19 > Proposed Mechanisms quote: More specific to POTS, adrenergic and muscarinic acetylcholine receptor autoantibodies, dysautonomia, small fiber neuropathies, platelet storage pool deficiencies, mast cell dysfunction with dysregulated histamine release as well as physical deconditioning have been implicated.31 note: 'Found by winnow, kev and lev in p015, p018, p010. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response. Few of the patients were detected to have autoantibodies to adrenergic, acetylcholine, and angiotensin II receptors [12,15].' note: 'Found by winnow, kev and lev in p012, p051, p079. Claude judged: supports.' - paper: pmid36947108 cited: true text: full license: none verdict: supports section: Dysautonomia in PASC > What do we know about autonomic dysfunction in PASC? quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Discussion quote: Autoimmunity with crossreactivity of antibodies against various viral illnesses towards ganglionic nicotinic acetylcholine receptors, alpha-1 and beta-1 and 2 adrenergic receptors, and angiotensin type II receptors can lead to POTS [9]. note: 'Found by winnow, kev and lev in p003, p015. Claude judged: supports.' - paper: pmid36873318 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: In recent years, autoimmunity has drawn attention as a potential cause of POTS in some patients.4,5 We and others have identified the presence of antiadrenergic autoantibodies in a subgroup of POTS patients.6, 7, 8 note: 'Found by winnow, kev and lev in p001, p007, p021. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Discussion quote: Although post-COVID-19 autonomic pathophysiology is complex and has not been fully elucidated, autoimmunity is thought to be a critical aspect of POTS. Several reports have demonstrated that COVID-19 antibodies cross-react with autonomic nervous system components, such as ganglia, nerve fibers, and G-protein-coupled receptors, which can trigger dysfunction [3,11]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: The aetiology is uncertain, but the hypothesis that, in some patients at least, POTS may be an autoimmune disease (AD) is currently being tested [4]. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid36414707 cited: true text: full license: by verdict: supports section: Discussion > Proinflammatory state in POTS quote: Growing evidence points toward POTS being an autoimmune disease, oftentimes triggered by a viral or bacterial infection28. note: 'Found by winnow, kev and lev in p001, p024, p027. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Discussion quote: Some cases of neuropathic POTS are thought to arise from immune-mediated neuropathy. note: 'Found by winnow, kev and lev in p037, p039. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: The pathophysiology of POTS remains unknown, however there is a number of physiological mechanisms that have been supposed to be involved. These may include sympathetic dysregulation, hypovolemia, hyperadrenergic stimulation, deconditioning12,57, autoantibody mediated response57, and mast cell activation58,59. note: 'Found by winnow, kev and lev in p007, p026. Claude judged: supports.' - paper: pmid36075372 cited: true text: full license: none verdict: supports section: Introduction > Other cardiovascular complications associated with COVID-19 vaccines > Arrhythmias quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36075372. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Selected Etiology: Autoimmune > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p066, p067, p062. Claude judged: supports.' - paper: pmid36000360 cited: true text: full license: by verdict: supports section: Discussion > POTS phenotypes quote: Additionally, autoantibodies against β1, β2, α1, M1, M2 receptors may be responsible for some cases of POTS [1,56]. note: 'Found by winnow, kev and lev in p058, p079. Claude judged: supports.' - paper: pmid35992935 cited: true text: full license: by verdict: supports section: Introduction quote: In recent years, an increasing number of studies reported the presence of autoantibodies against G-coupled protein receptors in patients with neuropathic POTS, suggesting an immune-mediated pathogenesis in a subset of these patients (Li et al., 2014; Fedorowski et al., 2017; Ruzieh et al., 2017; Watari et al., 2018; Gunning, et al., 2019). note: 'Found by winnow, kev and lev in p005, p025. Claude judged: supports.' - paper: pmid35870086 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p013. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p009, p014. Claude judged: supports.' - paper: pmid35852546 cited: true text: full license: none verdict: supports section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Plausibilität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid35766055 cited: true text: full license: by-nc-nd verdict: supports section: 'Abstract > Background:' quote: The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. note: 'Found by winnow, kev and lev in p001, p032, p005. Claude judged: supports.' - paper: pmid35725868 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005, p006. Claude judged: supports.' - paper: pmid35680184 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35680184. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Inflammation and Autoimmunity quote: In addition, the role for the autoimmune system and inflammation in the aetiology of POTS is supported by the increased antibodies and incidence of autoimmune conditions seen in patients with POTS compared to controls (46). note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What is the pathophysiology of POTS? quote: Postural orthostatic tachycardia syndrome may have an immunological cause. Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid35269395 cited: true text: full license: by verdict: supports section: Abstract quote: The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid35118574 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35118574. Found by winnow, kev and lev in p001, p004, p005. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS quote: Although the exact cause of POTS is unknown at this time, autoimmunity, hypovolemia, genetics, and a dysregulation of the autonomic nervous system are all thought to play a role in the syndrome.11 note: 'Found by winnow, kev and lev in p009, p011. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: There is evidence suggesting a major role for autoimmunity in the pathophysiology of post-viral POTS [73]. Patients with POTS have been shown to have a higher prevalence of specific autoantibodies (AAbs), including G-Protein coupled receptor (GPCR) antibodies, which could explain an increase in sympathetic tone by activating adrenergic receptors and eliciting a negative allosteric effect on muscarinic GPCRs [74,75]. note: 'Found by winnow, kev and lev in p025, p022. Claude judged: supports.' - paper: pmid34729276 cited: true text: full license: by verdict: supports section: Discussion quote: 'Most patients with POTS have elevated autoantibodies to at least one of a wide range of receptors associated with autonomic function: adrenergic receptors (beta1 and beta2), muscarinic receptors (M2 and M4), acetylcholine receptors (N type and P/Q type), opioid-like 1 receptors, and angiotensin II type 1 receptors [8]. These biomarkers in patients with POTS reinforce the notion that there is an autoimmune component to its pathophysiology.' note: 'Found by winnow, kev and lev in p009, p010. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Introduction quote: Besides hypovolemia, anemia, neurodegenerative aspects and connective tissue disorders, autoimmunity seems to play an important role in the pathogenesis of PoTS in some patients [[3], [4], [5], [6], [7]]. note: 'Found by winnow, kev and lev in p006, p009, p023. Claude judged: supports.' - paper: pmid34409582 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34409582. Found by winnow, kev and lev in p001, p002, p004. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Putative Mechanisms for Symptomatic Tachycardia in Post-COVID-19 Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid34275953 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34275953. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid34265539 cited: true text: full license: none verdict: supports section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Immune-mediated mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid34246578 cited: true text: full license: by-nc-nd verdict: supports section: Pathophysiology of POTS quote: These autoantibodies have been proposed to be a unifying mechanistic explanation for the cardiovascular changes in POTS, but the role of these antibodies remains unclear. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Role of immunotherapy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p023, p033. Claude judged: supports.' - paper: pmid34127505 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34127505. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid34117922 cited: true text: full license: by verdict: supports section: Conclusion quote: The papers discussed in this month’s journal club build upon previous work exploring autoimmunity as a causal factor in a sub-population of patients with POTS disease. note: 'Found by winnow, kev and lev in p002, p004, p019. Claude judged: supports.' - paper: pmid34055446 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Causes of POTS include abnormal blood pressure regulation, impaired nerve function, and autoimmune conditions. note: 'Found by winnow, kev and lev in p011, p002, p010. Claude judged: supports.' - paper: pmid34035985 cited: true text: full license: by verdict: supports section: Discussion quote: Primary partial dysautonomia (or neurogenic) POTS is thought to a pathologic immune-mediated response via serum auto-antibodies to α1-adrenergic receptors in vascular smooth muscle, muscarinic M4 receptors, and α3-Ach receptors on peripheral ganglia.4 note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Introduction quote: Some of the common causes of the disorder include the hypothalamus-pituitary-adrenal axis dysfunction, mitochondrial and mast cell disorders, cardiac sympathetic dysautonomia, irregular activation of the renin-angiotensin system, or a baroreflex dysfunction [3,4]. However, proposed mechanisms suggest an autoimmune basis with autoantibodies toward alpha-1 adrenergic receptors, beta-1/beta-2 receptors, M1/M2 muscarinic receptors, and ganglionic N-type acetylcholine receptors [3-5]. note: 'Found by winnow, kev and lev in p001, p008, p003. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Fazit für die Praxis quote: COVID-19, das multisystemische Inflammationssyndrom bei Kindern (MIS-C) und das posturale orthostatische Tachykardiesyndrom (POTS) nach COVID-19 sind durch Veränderungen der Herzfrequenz und Herzratenvariabilität (HRV) gekennzeichnet, die auf eine Beteiligung des autonomen Nervensystems hinweisen.Ursächlich werden eine Schädigung des sog. cholinergen antiinflammatorischen Signalweges und die Bildung von Autoantikörpern gegen adrenerge- und muskarinerge Rezeptoren diskutiert und in unserem Fall tatsächlich nachgewiesen. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Fisiopatologia e as apresentações clínicas > Amiloidose quote: Estudos demonstraram que a teoria autoimune pode ser o mecanismo fisiopatológico das formas “idiopáticas” de algumas síndromes disautonômicas, como a falência autonômica pura (FAP), SPOT ou a síndrome da fadiga crônica.43 note: 'Found by winnow, kev and lev in p050, p047. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: INTRODUCTION quote: The syndrome has been postulated to have post-viral autoimmune activation as a possible etiology (3). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026, p004. Claude judged: supports.' - paper: pmid33562074 cited: true text: full license: by verdict: supports section: 1. Introduction quote: One of the first reports of elevated autoantibodies in dysautonomia was reported by Vernino and co-workers, who proposed that ganglionic acetylcholine receptor (AChR) autoimmunity may cause the condition [12]. A series of subsequent publications by this group led them to suggest that a substantial percentage of POTS cases might be autoimmune [13,14,15,16]. note: 'Found by winnow, kev and lev in p002, p003, p005. Claude judged: supports.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: A growing body of evidence has shown that POTS may have an autoimmune basis. Multiple studies have shown various autoantibodies in conditions leading to dysautonomia.4,5 Therefore, it was hypothesized that autoantibodies against adrenergic and muscarinic receptors may play a prominent role in the pathophysiology of POTS.6 note: 'Found by winnow, kev and lev in p006, p001, p007. Claude judged: supports.' - paper: pmid33316414 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Discussion quote: There are reports suggesting that POTS may be an autoimmune disorder.13–15 In one study, POTS patients had elevated levels of autoantibodies that cross-reacted with beta and muscarinic receptors and resulted in tachycardia.15 note: 'Found by winnow, kev and lev in p010, p011. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Discussion quote: Gunning III et al. demonstrated antibodies to alpha-1 adrenergic receptors in 89% and M4 anti-acetylcholine receptor antibodies in 53% of a cohort of 55 patients [17]. These studies support an autoimmune basis in a substantial number of POTS patients, opening up a window for potential immunotherapy in refractory POTS patients. note: 'Found by winnow, kev and lev in p007, p025. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots > Autoimmune Dysfunction quote: Autoimmune disturbance has been considered as one of the mechanisms involved in POTS due to frequent findings of autoantibodies in patients (11, 86, 87). note: 'Found by winnow, kev and lev in p007, p019. Claude judged: supports.' - paper: pmid32848537 cited: true text: full license: by verdict: supports section: Discussion quote: The autoimmune hypothesis of POTS etiology could be a link between immune triggers, such as viral and bacterial infections, or vaccinations, as patients often identify a triggering factor with the beginning of symptoms. Presence of other autoimmune disorders has been reported in 20% of POTS patients (Blitshteyn, 2015). note: 'Found by winnow, kev and lev in p037. Claude judged: supports.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: It has been observed that some patients develop POTS following an infection. This observation has given rise to the hypothesis of an autoimmune‐mediated cause of POTS. note: 'Found by winnow, kev and lev in p016, p018, p031. Claude judged: supports.' - paper: pmid32743496 cited: true text: full license: by verdict: supports section: Discussion > Adrenergic receptor AAb activity in POTS quote: This allosteric impact is potentially greater than the direct orthosteric effects, and we believe this allosteric modulation is involved in the pathophysiology of POTS [7]. These indirect effects are not measured with our standard assay. note: 'Found by winnow, kev and lev in p007, p035, p036. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Neuropathic Pots: Midodrine and Pyridostigmine' quote: Neuropathic POTS is regarded as a restricted autoimmune autonomic ganglionopathy (AAG), associated with auto-antibodies in the ganglionic acetylcholine receptor (30, 31). note: 'Found by winnow, kev and lev in p011, p026. Claude judged: supports.' - paper: pmid32477718 cited: true text: full license: by verdict: supports section: Discussion quote: A separate study by the Mayo Clinic5 aiming to evaluate the prevalence and pathogenetic mechanisms of POTS found that, in a population of 152 patients, at least half of the cases had a neuropathic basis and that a substantial percentage of cases could be of autoimmune origin (ie, at least one in seven patients). note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid32321428 cited: true text: full license: by verdict: supports section: Background quote: Beyond genetic norepinephrine transporter deficiency, several theories have been proposed for the syndrome’s etiology, including antiadrenergic autoimmunity [2–4], baroreflex dysfunction [5], deconditioning [6], abnormal mast cell activation [1], excessive sympathetic drive and/or sympathetic denervation [7]. note: 'Found by winnow, kev and lev in p026, p005. Claude judged: supports.' - paper: pmid31547756 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: There is an emerging body of evidence that suggests an autoimmune basis for POTS.3 Several studies have investigated the presence of autoantibodies in POTS and their effects on cholinergic and adrenergic receptors.3 note: 'Found by winnow, kev and lev in p003, p004, p005. Claude judged: supports.' - paper: pmid31547749 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Background quote: Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. note: 'Found by winnow, kev and lev in p001, p003, p005. Claude judged: supports.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Background quote: A growing body of evidence suggests that POTS may be an autoimmune disorder. Antinuclear antibodies and elevations of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies have all been reported. note: 'Found by winnow, kev and lev in p001, p003, p004. Claude judged: supports.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: An autoimmune etiology in POTS is suggested by a number of clinical features (e.g., female predominance, preceding viral illness, prior vaccination history, and coexistence of other autoimmune conditions) along with autoantibodies.6 Antibody‐mediated autoimmune disorders usually have an HLA class II association.7 note: 'Found by winnow, kev and lev in p002, p014, p015. Claude judged: supports.' - paper: pmid31001074 cited: true text: full license: by verdict: supports section: Introduction quote: This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al., 2015; Watari et al., 2018) support this hypothesis. It has already been established that activating autoantibodies (AAb) to the α1-adrenergic (α1AR), β1/2-adrenergic receptors (β1/2AR), and angiotensin-receptor type 1 can be found in serum from POTS patients but not in controls (Fedorowski et al., 2017; Yu et al., 2018). note: 'Found by winnow, kev and lev in p003, p005, p027. Claude judged: supports.' - paper: pmid30883381 cited: true text: full license: by-nc verdict: supports section: 'Comments > Two common causes of hemodynamic orthostatic dizziness/vertigo: OH versus POTS' quote: Some patients with POTS have anti-ganglionic (α3) acetylcholine receptor antibody, suggesting a limited form of autoimmune autonomic neuropathy [46]. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid30372565 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30372565. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: In some individuals, including those with postconcussive onset of POTS symptoms, POTS may be the consequence of an autoimmune mediated autonomic neuropathy, which may require treatment targeted to the autoimmune condition in addition to exercise and other standard POTS treatments. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: An autoimmune basis has been suggested as a causal mechanism of POTS, and several autoreactive IgGs have been identified, including ganglionic acetylcholine receptor (gAChR), voltage‐gated potassium channel complex, cardiac lipid raft‐associated proteins, α1‐adrenergic receptor, as well as β1‐ and β2‐adrenergic receptors.5, 6, 7 note: 'Found by winnow, kev and lev in p003, p001, p015. Claude judged: supports.' - paper: pmid29618472 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.6 Immune-Mediated quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Autoimmunity and mast cell activation syndromes have been postulated as contributing to the development of POTS in some patients, but immunotherapy is rarely indicated and the relevance of autoantibodies and mast cells in most patients with POTS remains controversial.3–5 note: 'Found by winnow, kev and lev in p003, p020. Claude judged: supports.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: supports section: Abstract > Aims quote: To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Autoimmune/Autoantibodies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p031, p032. Claude judged: supports.' - paper: pmid25087056 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25087056. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p068, p044. Claude judged: supports.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: supports section: Abstract > Background quote: Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR). note: 'Found by winnow, kev and lev in p001, p003, p006. Claude judged: supports.' - paper: pmid24102827 cited: true text: abstract license: none verdict: supports section: Abstract > Background And Purpose quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24102827. Found by winnow, kev and lev in p003, p001. Claude judged: supports.' - paper: pmid23562385 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23562385. Found by winnow, kev and lev in p001, p014, p016. Claude judged: supports.' - paper: pmid23002038 cited: true text: full license: none verdict: supports section: 4 Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23002038. Found by winnow, kev and lev in p004, p005, p019. Claude judged: supports.' - paper: pmid19058765 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Introduction and background quote: The research does not support the notion that a single mechanism is responsible for the development of cognitive symptoms, since POTS is a diverse syndrome with possible hypovolemic, neuropathic, hyperadrenergic, autoimmune, and post-viral subtypes. note: 'Found by winnow, kev and lev in p017, p007, p060. Claude judged: partial.' - paper: pmid42512077 cited: true text: full license: by verdict: partial section: 1. Introduction quote: While the pathogenesis of POTS remains incompletely understood, the current literature has documented the presence of circulating autoantibodies in affected patients [15,16]. note: 'Found by winnow, kev and lev in p006, p005. Claude judged: partial.' - paper: pmid42037722 cited: true text: full license: by verdict: partial section: Mechanistic phenotypes supporting a compensatory framework > Immune-mediated mechanisms quote: 'These findings support immune-mediated perturbations of autonomic signaling in selected patients. Yet orthostatic tachycardia can still represent a compensatory final common pathway: immune-mediated vasomotor impairment or receptor-level signaling changes reduce effective vascular resistance or venous return, and HR rises to preserve perfusion.' note: 'Found by winnow, kev and lev in p001, p026. Claude judged: partial.' - paper: pmid41103515 cited: true text: full license: by verdict: partial section: Differential diagnosis of OD with PPPD > Hemodynamic orthostatic dizziness > Postural orthostatic tachycardia syndrome quote: Some patients with POTS possess anti-ganglionic (α3) acetylcholine receptor antibodies, indicating a limited form of autoimmune autonomic neuropathy (16). note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Finally, COVID-19 may trigger development of autoantibodies, including antiphospholipid antibodies or antibodies against adrenergic and muscarinic receptors, that could then contribute to the cardiovascular manifestations of LHC (11, 13). note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid39447442 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39447442. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid38464711 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Another major hypothesis is molecular mimicry and its autoimmune response, specifically G-protein-coupled receptors antibodies, which can cause an increased sympathetic tone [5, 20]. The autoimmune mechanism has been theorized to be associated with COVID-19-related POTS as well, and the data could also be an explanation of the higher prevalence in women due to the pathophysiology behind autoimmune diseases. note: 'Found by winnow, kev and lev in p039. Claude judged: partial.' - paper: pmid38396973 cited: true text: full license: by verdict: partial section: 2. Presence of Autoantibodies to gAChR and the Pathomechanism Causing Autonomic Dysfunction quote: We mentioned the agonistic mechanism of autoantibodies when we reported on autoimmunity in postural orthostatic tachycardia syndrome (POTS) [20]. This discussion was inspired by a report at the time, in the same research field, of the presence of autoantibodies that activate receptors in patients with POTS [21,22]. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid37400156 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37400156. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid37388279 cited: true text: full license: by verdict: partial section: 'Long Covid symptoms, effect on organs, and pathological mechanisms > Autonomic system sequelae > Mechanisms of autonomic dysfunction > Autoimmune attack:' quote: It is speculated that autoimmune mechanisms and autoantibody formation may be involved in the manifestation of autonomic symptoms in long Covid (121). It has also been shown that postural tachycardia syndrome and orthostatic hypotension are associated with these processes (122). note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37378800 cited: true text: full license: by verdict: partial section: Discussion quote: Watari et al. found that anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies occurred more frequently in patients with POTS compared to HCs, suggesting that anti-gAChR antibodies may be associated with POTS and its underlying autonomic [32]. note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid37255928 cited: true text: full license: by verdict: partial section: Auto-antibodies in POTS and Long Covid—significance and implications for future study quote: Antibodies to the α- and β- adrenoceptors may exert effects in POTS by either impaired vasoconstriction (mediated by α-adrenoceptors in the peripheral vasculature) resulting in venous pooling and reduced cardiac venous return) or positive chronotropic effects, exacerbating postural heart rate rise [11]. note: 'Found by winnow, kev and lev in p020, p009, p021. Claude judged: partial.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: COVID-19 vaccination induced autoimmunity quote: Autoimmunity may be the key pathogenetic pathway of post-vaccination POTS-like symptoms, particularly with adjuvanted mRNA vaccines. note: 'Found by winnow, kev and lev in p011, p019, p029. Claude judged: partial.' - paper: pmid36732397 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: Molecular mimicry between microbial agents and the human host hypothetically plays a role in the development of autoimmunity. In the three cases of postvaccination POTS, the symptoms and signs were almost identical to those of PASC, indicating that COVID-19 vaccines share the same target autoantibody epitope with PASC presenting as immune-mediated POTS. note: 'Found by winnow, kev and lev in p013, p007. Claude judged: partial.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Autonomic dysfunction in POTS could also be a result of the virus itself or the immune response it stimulates, with immune-mediated neurological syndromes having been described.8 In addition, there may also be an association with POTS and autoantibodies following COVID-19 illness,9 which suggests an autoimmune component to PASC and POTS. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid36509178 cited: true text: full license: none verdict: partial section: Discussion > Hospitalization status quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36509178. Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Discussion quote: Although the exact mechanism of vaccine-induced POTS is not clear, the autoimmune pathophysiology might be a key component [13-15]. note: 'Found by winnow, kev and lev in p001, p014, p004. Claude judged: partial.' - paper: pmid35937046 cited: true text: full license: by verdict: partial section: Postural orthostatic tachycardia syndrome and its possible effect on LQTS quote: The underlying mechanism of POTS after COVID-19 vaccines is still unclear. Either autoantibodies against α1-adrenergic receptors in the cardiovascular system or diminished response to angiotensin II contributes to the impairment of vasoconstriction and induced postural tachycardia. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid35062788 cited: true text: full license: by verdict: partial section: 6. Discussion quote: Furthermore, with cohorts of POTS patients recently being found to have adrenergic or muscarinic autoantibodies [36,77,78], and given known MC surface expression of adrenergic and muscarinic receptors which are active in the regulation of MC function [36], it even becomes possible, at least in theory, to drive MC activation (and thus at least those types of POTS underpinned by MCAS) via such autoantibodies as well. note: 'Found by winnow, kev and lev in p020, p021. Claude judged: partial.' - paper: pmid34993884 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34993884. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: partial section: Discussion quote: It can be speculated from previous studies that autonomic nervous dysfunction in patients diagnosed with comorbidities of POTS and chronic fatigue syndrome may be related to autoantibodies against G-protein-coupled receptors and small fiber neuropathy.41–43 However, at present, the exact role of these antibodies is not fully understood. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid33382525 cited: true text: abstract license: none verdict: partial section: Abstract > Background And Purpose quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33382525. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid29682372 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The Mayo Clinic experience study showed some correlation between autoimmunity and POTS. This study entails specific antibodies, such as ganglionic acetylcholine receptor antibody [8] and alpha-1 adrenergic receptor antibody that act as partial antagonists and induce reflex compensatory sympathetic activation [9]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid27638661 cited: true text: full license: by-nc verdict: partial section: Discussion quote: These results could explain the variety of labels that have been used to explain this symptomatology, as autoantibodies to these receptors have been previously linked with CRPS, POTS, and CFS [28–31]. note: 'Found by winnow, kev and lev in p035. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: The absence of a distal to proximal gradient in sudomotor deficits, observed by us and by others lends additional support to the possibility that an immune-mediated process underlies neuropathic POTS [5,8,37]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p034. Claude judged: partial.' - edge: - hypovolemic_evidence - proposed_mechanism_of - pots papers: 89 evidence: - paper: pmid42342500 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42342500. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: Hypovolemia is common in POTS and plays a central role in developing a rapid heart rate, even with normal blood pressure. note: 'Found by winnow, kev and lev in p030, p031, p029. Claude judged: supports.' - paper: pmid42037722 cited: true text: full license: by verdict: supports section: Introduction quote: Despite consistent diagnostic criteria, POTS is mechanistically heterogeneous. Major reviews emphasize roles for hypovolemia, venous pooling, deconditioning, peripheral autonomic neuropathy, hyperadrenergic states, and immune-mediated mechanisms. note: 'Found by winnow, kev and lev in p015, p007, p017. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: These patients have comparatively reduced levels of standing plasma renin activity and aldosterone, which can contribute to systemic volume dysregulation [5]. Relative hypovolemia in this case or following either poor fluid intake or loss of fluids due to gastrointestinal disorders can lead to the development of secondary orthostatic intolerance and eventually POTS [5]. note: 'Found by winnow, kev and lev in p012, p018. Claude judged: supports.' - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Discussion > Cardiovascular determinants quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p009, p031. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Introduction quote: The precise pathophysiology of POTS is not fully understood but several factors may contribute, including hyperadrenergic stimulation, hypovolemia, peripheral autonomic neuropathy, and autoimmunity.6 note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40626134 cited: true text: full license: by verdict: supports section: Abstract quote: Central hypovolemia, peripheral vascular dysfunction, and a hyperadrenergic state may contribute to the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p001, p003, p007. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: Abstract quote: Our findings demonstrate that an insufficient cerebral blood supply, driven by hypovolemia and impaired vascular compliance, combined with autonomic dysregulation, underlies the hallmark tachycardia in Postural Orthostatic Tachycardia Syndrome. note: 'Found by winnow, kev and lev in p001, p003, p008. Claude judged: supports.' - paper: pmid39614968 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. note: 'Found by winnow, kev and lev in p035, p004, p005. Claude judged: supports.' - paper: pmid39268060 cited: true text: full license: by verdict: supports section: Overview of POTS > Proposed mechanisms underlying POTS quote: Several mechanisms have been proposed as the potential pathophysiology behind POTS and are often labeled as the sub-types of neuropathic, hyperadrenergic and hypovolemic POTS (40). note: 'Found by winnow, kev and lev in p033, p036. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: 'Thoracic hypovolemia: While dysautonomia is a core feature, a crucial aspect of understanding POTS is the concept of thoracic hypovolemia, where a reduction in blood volume within the thoracic cavity leads to a diminished venous return [3].' note: 'Found by winnow, kev and lev in p011, p020, p013. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome quote: POTS is theorized to be the culmination of multiple underlying pathological processes, including peripheral neuropathy/denervation, hypovolemia with altered renin–aldosterone levels, and a hyperadrenergic state. note: 'Found by winnow, kev and lev in p009, p010. Claude judged: supports.' - paper: pmid38328599 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Hypovolemic postural orthostatic tachycardia syndrome (POTS) is thought to be caused by dysregulated circulating blood volume. note: 'Found by winnow, kev and lev in p001, p005. Claude judged: supports.' - paper: pmid38171114 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: For those with a reduced blood volume as the main mechanism, due to the reduced blood volume, they cannot be successfully compensated by increasing the cardiac output during long-term standing, thereby triggering reflexive tachycardia and consequently developing POTS.4 note: 'Found by winnow, kev and lev in p007, p040, p039. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Introduction quote: Hypovolemic POTS is due to dysfunction of the renin–angiotensin–aldosterone system resulting in low plasma blood volume and may be identified with 24-h urine sodium concentration less than 100 mmol/L1. note: 'Found by winnow, kev and lev in p004, p023. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: POTS could result from mild autonomic neuropathy, hypovolemia and abnormal renin-aldosterone response, and genetic or acquired deficiency of norepinephrine receptors leading to a hyperadrenergic state [15]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: 1. Introduction quote: POTS in children can result from several pathophysiological mechanisms, including peripheral vascular dysfunction, hypovolemia, autonomic dysfunction, a hyperadrenergic state, impaired skeletal-muscle pump activity, and autoimmune dysfunction [8,9,10]. note: 'Found by winnow, kev and lev in p010, p003, p005. Claude judged: supports.' - paper: pmid37443510 cited: true text: full license: by verdict: supports section: 4. Discussion quote: POTS is caused by cerebral hypoperfusion in the brain due to a relative lack of blood volume, thus inducing orthostatic intolerance symptoms. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: In the majority of patients, intravascular volume is reduced, thus leading to decreased venous return to the heart and causing reflex tachycardia and orthostatic intolerance. note: 'Found by winnow, kev and lev in p005, p001. Claude judged: supports.' - paper: pmid37393658 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p006, p026, p001. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Introduction and background quote: The mechanisms proposed to explain POTS include autonomic neuropathy, increased sympathetic tone, a hypovolemic state with an altered renin-angiotensin-aldosterone system, and autoimmunity [13-17]. note: 'Found by winnow, kev and lev in p011, p003, p020. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: Various pathophysiologic mechanisms of POTS exist, but some common ones include hypovolemia, autoimmunity, and neuropathy. Reduction in intravascular volume can result in decreased venous return to the heart and lead to reflex tachycardia. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: The pathophysiology of POTS remains unknown, however there is a number of physiological mechanisms that have been supposed to be involved. These may include sympathetic dysregulation, hypovolemia, hyperadrenergic stimulation, deconditioning12,57, autoantibody mediated response57, and mast cell activation58,59. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p005, p017. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.2. Physiological Predictors for the Oral Rehydration Salts Efficacy in Pediatric POTS quote: One of the major underlying causes of POTS is hypovolemia. note: 'Found by winnow, kev and lev in p026, p003, p010. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Hypovolaemia quote: Firstly, it has been suggested that POTS occurs due to decreased blood volume and deconditioning of the heart, which subsequently increases cardiac sympathetic nervous system (SNS) output (24, 32, 33). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: According to the current points of view, relative central hypovolemia, autonomic nervous dysfunction, and peripheral vascular dysfunction are speculated to be the mechanisms for POTS,30 which may be enhanced by complications with comorbidities. note: 'Found by winnow, kev and lev in p023, p031. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Hypovolemia may trigger hyperadrenergic POTS and lead to cerebral hypoperfusion and the impairment of central autonomic networks [56]. note: 'Found by winnow, kev and lev in p022, p023. Claude judged: supports.' - paper: pmid34746821 cited: true text: full license: by-nc-nd verdict: supports section: Introduction > Carotid body – a unifying hypothesis? quote: 'Central hypovolemia is a cardinal feature of POTS: evidence supports excessive reduction of central blood volume in typical POTS patients when upright and we demonstrated that central blood volume is reduced in POTS (Stewart et al., 2018a). This predisposes patients to hypoperfusion of tissues cephalad to the heart, causing stagnant hypoxia from reduced carotid blood flow – a key step causing SNA activation (Marshall, 1994; Prabhakar et al., 2005) in the pathophysiologic cascade in POTS.' note: 'Found by winnow, kev and lev in p006, p001, p010. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Introduction > Definition of postural orthostatic tachycardia syndrome quote: The onset of POTS has been attributed to dysautonomia, hypovolemia, deconditioning, a hyperadrenergic physiologic state, hypervigilance (unusual focus on bodily sensations), or any combination of these conditions.1 note: 'Found by winnow, kev and lev in p004, p015. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p014, p017, p019. Claude judged: supports.' - paper: pmid34055686 cited: true text: full license: by verdict: supports section: Discussion quote: Another acknowledged mechanism is central hypovolemia (1, 2). note: 'Found by winnow, kev and lev in p026, p027. Claude judged: supports.' - paper: pmid33926653 cited: true text: full license: none verdict: supports section: DISCUSSION > Low Blood Volume in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p045, p009, p010. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots > Altered Central Blood Volume quote: When hypovolemia exists at rest, the body cannot fully compensate for the decrease in blood volume after standing (27), which has to coexist with elevated HR in the upright position (28). Paradoxically, normal plasma volumes in patients with POTS have been reported (29, 30), indicating that hypovolemia is not the unique cause of POTS. note: 'Found by winnow, kev and lev in p008, p009, p010. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: Pots Subtypes in Children and Adolescents > Hypovolemic POTS quote: Central hypovolemia leads to a decrease in venous return, resulting in an increase of heart rate as compensation. Low blood volumes have been observed in many children and adolescents with POTS (23, 24). note: 'Found by winnow, kev and lev in p010, p011, p018. Claude judged: supports.' - paper: pmid32612820 cited: true text: full license: by verdict: supports section: Introduction quote: The pathophysiology remains unknown but many theories have been described including hypovolemia, autonomic dysfunction, hyperadrenergic state, adrenergic receptor deficiency, mast cell activation, renin-aldosterone paradox and physical deconditioning [10]. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid32112609 cited: true text: full license: by verdict: supports section: DISCUSSION quote: The main pathogenesis of POTS is hypovolemia, autonomic nervous dysfunction, hyperadrenergic, muscle pump dysfunction, and vascular endothelial dysfunction. These mechanisms can appear to co‐exist (Raj, 2013; Sheldon et al., 2015; Thanavaro & Thanavaro, 2011). note: 'Found by winnow, kev and lev in p018, p006. Claude judged: supports.' - paper: pmid31384930 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Several potential underlying mechanisms have been suggested for POTS including autonomic denervation, hypovolaemia, hyperadrenergic stimulation, and autoantibodies against adrenergic receptors.2,3 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p002, p001, p014. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: PATHOPHYSIOLOGY OF POTS quote: Hypovolemia is often a contributing factor in POTS, as plasma volume, red cell volume, and total blood volume are reduced compared with control subjects in studies.28,38 In POTS, the renin-angiotensin-aldosterone system responsible for the regulation of plasma volume does not function properly, impairing the typical water and sodium retention needed to build plasma volume.39 note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.4 Hypovolemia quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid27660311 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27660311. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: 'Abstract > Conclusions:' quote: The pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. note: 'Found by winnow, kev and lev in p004, p005, p007. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Physiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p011, p013. Claude judged: supports.' - paper: pmid25792354 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25792354. Found by winnow, kev and lev in p022, p004. Claude judged: supports.' - paper: pmid25713509 cited: true text: full license: by verdict: supports section: Neurovisceral phenotypes > Postural Tachycardia Syndrome > Clinical picture and autonomic dysfunction quote: However, hypovolemia, abnormalities of the noradrenaline transporter (Esler et al., 2006; Lambert et al., 2008; Bayles et al., 2012), infection (Schondorf and Low, 1993), deconditioning (Parsaik et al., 2012), and poor orthostatic cerebral autoregulation (Ocon et al., 2009) are also implicated in Postural Tachycardia Syndrome pathophysiology. note: 'Found by winnow, kev and lev in p009, p021. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: Abstract quote: Another common pathophysiological mechanism in POTS is a hypovolemic state. Many POTS patients with a hypovolemic state have been found to have a perturbed renin-angiotensin-aldosterone profile. note: 'Found by winnow, kev and lev in p009, p001, p004. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p072, p040. Claude judged: supports.' - paper: pmid22721633 cited: true text: full license: none verdict: supports section: 4. Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22721633. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid22247480 cited: true text: full license: none verdict: supports section: Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22247480. Found by winnow, kev and lev in p030, p006. Claude judged: supports.' - paper: pmid21266211 cited: true text: full license: none verdict: supports section: Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21266211. Found by winnow, kev and lev in p029, p001, p007. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: supports section: Abstract > Objectives quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p035, p041, p001. Claude judged: supports.' - paper: pmid20479333 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20479333. Found by winnow, kev and lev in p002, p013, p015. Claude judged: supports.' - paper: pmid11201632 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11201632. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid42591853 cited: true text: full license: by verdict: partial section: ME/CFS as a low output syndrome due to small heart > Orthostatic intolerance (OI) (classical mechanism) quote: It has been reported that patients with postural orthostatic tachycardia, which is often observed in patients with chronic OI and/or ME, have a smaller heart coupled with reduced blood volume compared with healthy controls (53, 54). Using cardiac magnetic resonance imaging, Fu et al. (53) precisely assessed heart size, mass, and blood volume in POTS patients and found that all of these parameters were significantly lower compared with healthy sedentary controls. note: 'Found by winnow, kev and lev in p013, p021. Claude judged: partial.' - paper: pmid42114076 cited: true text: abstract license: none verdict: partial section: Abstract > Recent Findings quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42114076. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid42037960 cited: true text: full license: by verdict: partial section: Discussion quote: Hypovolemia, whether central or secondary to nutritional compromise, can drive the symptoms of POTS [6]. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid41976810 cited: true text: full license: by verdict: partial section: 1. Introduction quote: 'Sheldon et al. [6] summarise two possible mechanisms for PoTS: firstly, autonomic denervation leading to impaired peripheral venoconstriction, which leads to venous pooling, hypovolaemia, and hyperadrenergic stimulation with raised plasma norepinephrine levels, or, secondly, deconditioning, which may be compounded by anxiety and hypervigilance secondary to the underlying physiological abnormalities.' note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid41703216 cited: true text: full license: by verdict: partial section: Body quote: Other studies demonstrate small cardiac chamber size and low stroke volume, indicating reduced cardiac filling pressures and impaired venous return [3]. These hemodynamic abnormalities likely contribute to orthostatic tachycardia. note: 'Found by winnow, kev and lev in p002, p001. Claude judged: partial.' - paper: pmid40944681 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: The patient's marked tachycardia in both supine and standing postures with associated symptoms of orthostatic intolerance observed after starting tirzepatide may be linked to the combination of lower-than-normal plasma volume for her size, which could contribute to a small standing stroke volume, and the drug's action as a dual GIP and GLP-1 receptor agonist. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: partial section: CBF in OI > CBF in POTS quote: More than 50% of POTS participants presented with central hypovolemia, resulting primarily from blood sequestration within the splanchnic vasculature, leading to reduced upright cerebral blood volume. note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Cardiovascular deconditioning may be implicated in POTS via cardiac atrophy and hypovolemia causing reactive tachycardia.[9] note: 'Found by winnow, kev and lev in p009, p039. Claude judged: partial.' - paper: pmid39297140 cited: true text: full license: by-nc-nd verdict: partial section: Discussion > Impaired systemic hemodynamic status in POTS quote: Moreover, many patients with POTS have low blood volumes,2 which could also contribute to reduced stroke volume and, in turn, reduced brain perfusion. Further investigations into the role of peripheral venous hemodynamic status and impaired blood volume regulation as a mechanism driving postural ventilation are warranted. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 7. The Role of Fibrinaloid Microclots in POTS quote: Other mechanisms for POTS in long COVID may include:Relative hypovolemia secondary to inadequate peripheral vasoconstriction. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid38287400 cited: true text: full license: by verdict: partial section: Discussion quote: The “low-flow” POTS proposed by Stewart [24] is also characterized by a decrease in central blood volume, similar to the hemodynamic characteristics of the Su group. note: 'Found by winnow, kev and lev in p029, p031. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: Pathophysiology of POTS quote: A significant number of POTS patients demonstrate a state of chronic intravascular hypovolaemia.[3] Abnormal RAAS activity, characterised by inadequate aldosterone secretion by angiotensin II, is the main mechanism of hypovolaemia.[13] note: 'Found by winnow, kev and lev in p008, p010. Claude judged: partial.' - paper: pmid36000360 cited: true text: full license: by verdict: partial section: Discussion > POTS phenotypes quote: Several recent studies [1,3,11] speculate that POTS comprise multiple phenotypes including hyperadrenergic, neuropathic and hypovolaemic POTS. note: 'Found by winnow, kev and lev in p051, p079, p084. Claude judged: partial.' - paper: pmid34268642 cited: true text: full license: none verdict: partial section: Autonomic Disorders and Headache quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34268642. Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Discussion quote: A subset of patients with POTS has low levels of standing plasma renin activity, aldosterone, and blood volume as compared to normovolemic patients [10]. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid33316414 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid32983103 cited: true text: full license: by verdict: partial section: Pediatric VVS and/or POTS Comorbid With Allergic Diseases > Pathogenesis quote: At present, it is believed that several mutual mechanisms, including the relative central hypovolemia, the dysregulation of peripheral vascular tone, and the imbalance of sympathetic and vagal functions, can all reduce the cardiac output when one stands upright and ultimately result in syncope in children with VVS and/or POTS (18, 19). note: 'Found by winnow, kev and lev in p006, p008. Claude judged: partial.' - paper: pmid32494413 cited: true text: full license: by verdict: partial section: Dr. Mehdirad remarks > Mechanisms and symptoms quote: Hypovolemia or excessive lower-extremity and splanchnic venous pooling results in inadequate venous return, which may possibly explain some of the manifestations of POTS.14 note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid31798399 cited: true text: full license: by verdict: partial section: Introduction > Orthostatic Cardiovascular Responses Are Impaired in Patients With Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: Another contributor to most forms of orthostatic syncope in adults is hypovolemia, which may be associated with impaired renal sodium reabsorption in patients with POTS (Raj, 2013). note: 'Found by winnow, kev and lev in p015, p012. Claude judged: partial.' - paper: pmid31780890 cited: true text: full license: by verdict: partial section: Discussion quote: The pathogenesis of POTS is still unclear, possibly including autonomic dysfunction (Shannon et al., 2000), excessive vasodilation (Liao et al., 2013), and low central blood volume (Zhang et al., 2012). note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid31405524 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31405524. Found by winnow, kev and lev in p008, p028. Claude judged: partial.' - paper: pmid29876157 cited: true text: full license: by verdict: partial section: Review quote: Patients with this syndrome have a partial neuropathic state with impaired lower extremity sympathetic innervation, abnormal venous pooling, and hypovolemic state with low renin–angiotensin–aldosterone system upregulation [24]. A study showed that some patients with POTS had inappropriately normal levels of plasma renin activity and paradoxically lower levels of aldosterone despite their hypovolemia when compared to healthy subjects [25]. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid29682372 cited: true text: full license: by verdict: partial section: 3. Discussion quote: Several mechanisms have been proposed for the development of these symptoms including sympathetic denervation and central causes such as sympathetic overdrive, hypovolemia, and involvement of the renin-angiotensin-aldosterone system. note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid29451148 cited: true text: full license: by-nc-sa verdict: partial section: DISCUSSION quote: In 1940, MacLean and Allen first reported the presence of hypovolemia in children with POTS, and further studies revealed an increased venous capacity in the lower extremities of children with POTS attributable to the local anatomy and functional abnormality of the lower limbs.[1617] note: 'Found by winnow, kev and lev in p022. Claude judged: partial.' - paper: pmid27936059 cited: true text: full license: by verdict: partial section: Discussion quote: Convertino, et al. showed that low blood volume might cause increase in BRS [42]. When POTS patients change to upright position from supine position, returned blood volume decreases, and cardiac output decreases; at this time, if BRS increases abnormally, it would cause an over excitation caused by sympathetic nervous system reflectively when blood pressure of patients decreases slightly, thus to cause an over increase in heart rate of children at upright position. note: 'Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid26814068 cited: true text: abstract license: none verdict: partial section: Abstract > Objective quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26814068. Found by winnow, kev and lev in p001, p004. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Hemodynamic Physiology of Standing quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p004, p025, p024. Claude judged: partial.' - paper: pmid25483980 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid25474569 cited: true text: full license: by verdict: partial section: Introduction quote: Studies indicated that POTS patients, with hypovolemia, had inadequate venous return to the heart in an upright position [11]–[13]. note: 'Found by winnow, kev and lev in p029, p006, p027. Claude judged: partial.' - paper: pmid25168872 cited: true text: full license: by verdict: partial section: Discussion quote: Though we did not measure intravascular volume in our patients, one could propose, an alternative, cogent, and coherent, interpretation of these observations. Development of the POTS phenotype begins with abnormal sympathetic regulation of volume status via renin‐angiotensin system (Garland et al. 2007) leading to volume depletion. note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - paper: pmid23753844 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Hypovolemia & Blood Volume Regulation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p023, p015, p020. Claude judged: partial.' - paper: pmid16262605 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16262605. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid9244228 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 9244228. Found by winnow, kev and lev in p003. Claude judged: partial.' - edge: - neuropathic_evidence - proposed_mechanism_of - pots papers: 83 evidence: - paper: pmid42342500 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42342500. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid42037722 cited: true text: full license: by verdict: supports section: Introduction quote: Despite consistent diagnostic criteria, POTS is mechanistically heterogeneous. Major reviews emphasize roles for hypovolemia, venous pooling, deconditioning, peripheral autonomic neuropathy, hyperadrenergic states, and immune-mediated mechanisms. note: 'Found by winnow, kev and lev in p022, p001, p007. Claude judged: supports.' - paper: pmid41767063 cited: true text: full license: by verdict: supports section: Discussion quote: In neuropathic POTS, peripheral autonomic injury—primarily small‐fiber neuropathy—is a core mechanism. This peripheral denervation leads to impaired vasoconstriction in the lower extremities, resulting in excessive venous pooling during orthostatic stress, which “passively” triggers compensatory tachycardia. note: 'Found by winnow, kev and lev in p023, p025, p004. Claude judged: supports.' - paper: pmid41675297 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: This is generally differentiated from neuropathic POTS, which is felt to relate to redistributive central hypovolemia in the upright position as opposed to absolute hypovolemia. This is hypothesized to be due to small fiber neuropathy leading to decreased adrenergic vasoconstriction in the legs or the splanchnic vasculature, causing baroreflex unloading, decreased reflex cardiovagal stimulation, increased reflex sympathetic excitation, and reflex tachycardia.46 note: 'Found by winnow, kev and lev in p048, p059. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: This subtype of POTS is presumed to occur due to the impaired sympathetically mediated peripheral vasoconstriction, leading to venous pooling in the lower limbs. This sympathetic denervation can cause an impairment of sweating in the lower extremities and reduced release of norepinephrine [5]. note: 'Found by winnow, kev and lev in p016, p093. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Discussion quote: Small fiber neuropathy is regarded as one of the potential mechanisms underlying the pathophysiology of POTS [20], and in our cohort, QSART abnormalities indicating postganglionic small fiber dysfunction occurred with similar frequency in post-COVID and post-vaccination POTS. note: 'Found by winnow, kev and lev in p045. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 4 Discussion quote: The majority of POTS patients require numerous visits to several physicians of different disciplines to be accurately diagnosed due to the multitude of conflicting clinical symptoms (78–80). Hypotheses regarding pathophysiology include abnormally increased sympathetic activity, sympathetic denervation leading to hypovolemia and reflex tachycardia, and autoimmunity to G-protein coupled receptors (2, 3, 79, 81, 82). note: 'Found by winnow, kev and lev in p026, p024. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Introduction quote: The precise pathophysiology of POTS is not fully understood but several factors may contribute, including hyperadrenergic stimulation, hypovolemia, peripheral autonomic neuropathy, and autoimmunity.6 note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40608783 cited: true text: full license: by verdict: supports section: 4. Discussion quote: It is estimated that approximately 50% of the POTS population have a neuropathic mechanism behind their symptoms [2], although no diagnostic criteria for neuropathic POTS exist [9]. note: 'Found by winnow, kev and lev in p005, p036. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Migraine Headaches quote: Post-ganglionic sympathetic denervation and amplified sympatho– adrenomedullary axis activity are felt to be related to the pathophysiology of neurogenic and hyperadrenergic POTS, respectively. note: 'Found by winnow, kev and lev in p034, p027, p032. Claude judged: supports.' - paper: pmid39355826 cited: true text: full license: by verdict: supports section: Discussion quote: Despite similar clinical characteristics, POTS is likely a heterogeneous group of disorders. These include an autoimmune mechanism associated with antibodies to the postsynaptic acetylcholine receptors of the autonomic nerves, high levels of circulating norepinephrine as a result of a genetically determined malfunction of norepinephrine reuptake proteins, and importantly, a form of autonomic cardiac neuropathy. note: 'Found by winnow, kev and lev in p009, p007. Claude judged: supports.' - paper: pmid39268060 cited: true text: full license: by verdict: supports section: Overview of POTS > Proposed mechanisms underlying POTS quote: Several mechanisms have been proposed as the potential pathophysiology behind POTS and are often labeled as the sub-types of neuropathic, hyperadrenergic and hypovolemic POTS (40). note: 'Found by winnow, kev and lev in p034, p065, p033. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Sympathetic denervation, characterized by a decrease in sympathetic nerve activity, is another factor contributing to autonomic dysfunction in POTS [38]. This denervation disrupts the intricate coordination between the nervous and cardiovascular systems, ultimately giving rise to the hallmark symptoms of POTS. note: 'Found by winnow, kev and lev in p012, p013. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p005, p029. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p002, p024. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome quote: POTS is theorized to be the culmination of multiple underlying pathological processes, including peripheral neuropathy/denervation, hypovolemia with altered renin–aldosterone levels, and a hyperadrenergic state. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Symptoms and clinicopathologic features of dysautonomia quote: Neuropathic POTS is associated with reduced intraepidermal and/or sudomotor (i.e., sweat gland) nerve fiber density on skin biopsy indicative of a small-fiber sensory or autonomic neuropathy. It is hypothesized that damage to sympathetic vasomotor nerves impairs the compensatory increase in systemic vascular resistance during orthostatic stress and/or during exercise, resulting in splanchnic and/or lower limb pooling and reduced cerebral blood flow. note: 'Found by winnow, kev and lev in p006, p007, p017. Claude judged: supports.' - paper: pmid37968647 cited: true text: full license: by verdict: supports section: Introduction quote: Small fiber neuropathy (SFN) has been suggested to be a possible mediator of POTS [16]. SFN can affect both autonomic and sensory fibers [17]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 3. Etiopathogenic basis quote: The pathophysiological mechanisms resulting in autonomic dysfunction in POTS may include sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac sympathoexcitation response (hyperadrenergic POTS) with increased serum norepinephrine, volume dysregulation (hypovolemia), baroreceptor dysfunction, peripheral neuropathy, and autoimmunity due to molecular mimicry following infections by pathogens such as Epstein–Barr virus, cytomegalovirus, or Borrelia Burgdorferi (1, 15). note: 'Found by winnow, kev and lev in p006, p008. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: POTS could result from mild autonomic neuropathy, hypovolemia and abnormal renin-aldosterone response, and genetic or acquired deficiency of norepinephrine receptors leading to a hyperadrenergic state [15]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: 2. The Development of POTS and Its Associated Manifestations quote: Neuropathic POTS is characterized by reduced vessel vasoconstriction in the lower extremities. In neuropathic POTS, the dilation of blood vessels causes central blood to be redistributed while standing, leading to compensatory tachycardia in response to the orthostatic challenge [19]. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Abstract quote: This case report is about a patient with post-viral neuropathic POTS. Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia. note: 'Found by winnow, kev and lev in p003, p015, p001. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Introduction quote: Multiple subtypes of POTS have been proposed, including a neuropathic subtype estimated to be present in 50% of POTS patients [3]. In these patients, POTS is hypothesized to be a result of partial sympathetic denervation, which leads to inadequate vasoconstriction in the legs upon standing upright, provoking compensatory tachycardia [4]. note: 'Found by winnow, kev and lev in p005, p037, p007. Claude judged: supports.' - paper: pmid36111700 cited: true text: full license: by-nc verdict: supports section: Introduction quote: The precise aetiology of POTS remains unknown, although the haemodynamic changes are thought to reflect convergence of multiple pathophysiological processes including peripheral autonomic neuropathy, hypovolemia, elevated sympathetic tone, deconditioning and auto‐antibodies to cardiovascular receptors [7]. note: 'Found by winnow, kev and lev in p006, p027. Claude judged: supports.' - paper: pmid36000360 cited: true text: full license: by verdict: supports section: Methods > POTS phenotypes quote: Neuropathic POTS is caused by partial neuropathy of the lower body vasculature, which causes abnormal blood pooling in the lower extremities. note: 'Found by winnow, kev and lev in p050, p066, p079. Claude judged: supports.' - paper: pmid35992935 cited: true text: full license: by verdict: supports section: Introduction quote: Neuropathic POTS is the most common type and is thought to be caused by peripheral sympathetic noradrenergic denervation leading to increased venous pooling (Jacob et al., 2000; Peltier et al., 2010). note: 'Found by winnow, kev and lev in p005, p024. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mechanisms quote: Neuropathic mechanisms may play a pathophysiologic role in approximately one half of patients diagnosed with POTS and are thought to be due to partial autonomic denervation and failure of the vasculature of the lower extremities to maintain resistance while in an upright position.14,15 note: 'Found by winnow, kev and lev in p011, p017. Claude judged: supports.' - paper: pmid34674068 cited: true text: full license: by verdict: supports section: Background quote: Neuropathic POTS is characterized by dysfunction of the peripheral sympathetic nerves predominantly affecting the lower limbs. The consequently impaired peripheral vasoconstriction leads to excessive venous blood pooling during orthostasis [2, 4]. note: 'Found by winnow, kev and lev in p021, p004, p005. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p014, p017. Claude judged: supports.' - paper: pmid34127505 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34127505. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Results > Representative cases > Postural tachycardia syndrome > Patient 15 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p023, p039. Claude judged: supports.' - paper: pmid33764697 cited: true text: full license: by verdict: supports section: Discussion quote: Several lines of evidence support the concept that neuropathic POTS in some individuals is due to a restricted peripheral neuropathy; specifically, sympathetic denervation predominantly in the lower hemibody with preservation or relative preservation of cardiac sympathetic innervation. note: 'Found by winnow, kev and lev in p006, p007, p027. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026, p003. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Introduction quote: Neuropathic POTS is usually due to a partial autonomic neuropathy leading to impaired sympathetically-mediated vasoconstriction of the lower limbs, leading to venous pooling and impaired venous return. note: 'Found by winnow, kev and lev in p007, p022. Claude judged: supports.' - paper: pmid33150760 cited: true text: full license: by verdict: supports section: Body quote: The underlying pathophysiological mechanisms leading to POTS are not completely understood. However, it seems that there are two main types of POTS, the adrenergic and neuropathic type (10). note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: Pots Subtypes in Children and Adolescents > Neuropathic POTS quote: Partial autonomic neuropathy is the characteristics of this subtype of POTS. The main mechanism of this type of POTS is patchy denervation of the sympathetic fibers to the blood vessels in the extremities (28). note: 'Found by winnow, kev and lev in p011, p022, p026. Claude judged: supports.' - paper: pmid32477718 cited: true text: full license: by verdict: supports section: Discussion quote: A separate study by the Mayo Clinic5 aiming to evaluate the prevalence and pathogenetic mechanisms of POTS found that, in a population of 152 patients, at least half of the cases had a neuropathic basis and that a substantial percentage of cases could be of autoimmune origin (ie, at least one in seven patients). note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid32284866 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Neuropathic POTS, thought to account for at least half of cases,22 is characterised by distal, predominantly lower extremity denervation which may impair vasoconstriction and increase gravitational venous pooling. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid32222376 cited: true text: full license: none verdict: supports section: Etiology and the concepts of primary and secondary POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32222376. Found by winnow, kev and lev in p020, p003, p021. Claude judged: supports.' - paper: pmid31798399 cited: true text: full license: by verdict: supports section: Introduction > Orthostatic Cardiovascular Responses Are Impaired in Patients With Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: Indeed, some forms of POTS reflect selective neuropathy, with sympathetic denervation and impaired vascular resistance responses affecting the lower limbs (Raj, 2013). note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: PATHOPHYSIOLOGY OF POTS quote: Approximately 50% of people with POTS experience a partial sympathetic denervation of blood vessels in the lower extremities, resulting in a reduced vasoconstriction response during upright posture, sometimes referred to as neuropathic POTS.30,40 Impaired venous return upon standing causes blood pooling in the lower limbs and within the abdominal cavity, which lowers stroke volume and results in compensatory tachycardia and reduced exercise capacity. note: 'Found by winnow, kev and lev in p015, p031. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p003, p024, p014. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.1 Partial Sympathetic Neuropathy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p016, p015. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid27938459 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27938459. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid27660311 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27660311. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid26610893 cited: true text: full license: by-nc verdict: supports section: INTRODUCTION quote: The pathophysiological mechanisms underlying POTS are also diverse and multifactorial, and include hypovolemia,5 hyperadrenergic states,6 lower-extremity neuropathies,7 and deconditioning.8 note: 'Found by winnow, kev and lev in p005, p013. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p023, p019. Claude judged: supports.' - paper: pmid25120493 cited: true text: full license: by verdict: supports section: Conclusion quote: POTS on the other hand may involve sympathetic denervation in the lower limbs, a hyperadrenergic state and/or abnormalities in the NET. note: 'Found by winnow, kev and lev in p016, p020. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS (Table 1) quote: POTS is a heterogeneous syndrome with several different pathophysiological mechanisms that can result in the typical POTS presentation, and a few more common ones are highlighted in this manuscript (Figure 1) (Raj, 2013). Neuropathic POTS is a condition with a partial neuropathy where there is preferential denervation of sympathetic nerves in the lower limbs that may account for local/regional blood flow abnormalities including venous pooling (Jacob et al., 2000; Stewart et al., 2003). note: 'Found by winnow, kev and lev in p004, p005, p008. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p044, p068. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: supports section: Introduction quote: Several lines of evidence point to a restricted peripheral neuropathy, specifically, sympathetic denervation predominantly in the lower hemibody, as a cause of POTS in some individuals. note: 'Found by winnow, kev and lev in p040, p006, p030. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Pathogenesis of POTS is heterogenous and may include sympathetic hyperactivity with peripheral denervation, hypovolemia, and physical deconditioning [3]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid23244360 cited: true text: full license: none verdict: supports section: 'Common variant OI: POTS & postural VVS > Postural tachycardia syndrome' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23244360. Found by winnow, kev and lev in p018, p017. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > POTS Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p010, p017. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: 'Three main groups have been identified: neuropathic, hyperadrenergic and POTS related to deconditioning [1]. In the neuropathic form, a restricted autonomic neuropathy with partial sympathetic denervation is present and predominates in the lower limbs [6], with an inability of the peripheral vasculature to constrict in response to orthostatic stress.' note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Pathophysiology quote: Many authors speculate on the possible causes for this, including impaired venous innervation and/or reduced venous response to sympathetic stimulation.[3] This theory supports a neuropathy that mainly affects the lower extremities. note: 'Found by winnow, kev and lev in p010, p016. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: supports section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p034, p009. Claude judged: supports.' - paper: pmid20185461 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20185461. Found by winnow, kev and lev in p003, p007. Claude judged: supports.' - paper: pmid20035362 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p003, p018, p031. Claude judged: supports.' - paper: pmid17898925 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 17898925. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid17352367 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 17352367. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: Considering that POTS patients have high plasma NE levels, it would seem paradoxical that a neuropathy is proposed as an underlying process. Yet some of them have a form of dysautonomia, with preferential denervation of sympathetic nerves innvervating the lower limbs [22-24]. note: 'Found by winnow, kev and lev in p024, p027, p042. Claude judged: supports.' - paper: pmid12577219 cited: true text: abstract license: none verdict: supports section: Abstract > Method quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 12577219. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid11408377 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11408377. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid11018167 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11018167. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid9868411 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 9868411. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid9848003 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 9848003. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid8423877 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 8423877. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: Small fiber neuropathy, characterized by damage to the small nerve fibers that control autonomic functions, is often associated with conditions like diabetes and autoimmune diseases, and its emergence in post-COVID-19 patients suggests a potential neuropathic component to the pathophysiology of Long-COVID POTS. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 7. The Role of Fibrinaloid Microclots in POTS quote: Small fiber neuropathy (SFN) has been well described in long COVID (e.g., [63,65,68,172]) and is a recognized cause of dysautonomia in the condition. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid37435242 cited: true text: full license: by verdict: partial section: Discussion quote: A small fiber neuropathy may be present in up to 50% of POTS cases and contributes to dysautonomia as seen in our patient. note: 'Found by winnow, kev and lev in p003, p004, p006. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Neurotropism quote: Thus, it has been proposed that SARS-Cov2 could infect and damage extracardiac postganglionic SNS, leading to dysautonomia in a similar way to neuropathic POTS. This disruption could lead to tachycardia due to splanchnic venous pooling or reduced mesenteric vasoconstriction during orthostasis (24). note: 'Found by winnow, kev and lev in p008, p006. Claude judged: partial.' - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Introduction quote: Moreover, small fiber neuropathy (SFN, neuropathic PoTS) could be detected in around 50 % of patients with PoTS [[8], [9], [10]]. Small fiber neuropathy preferentially affects unmyelinated C-fibers, thinly myelinated A-δ somatosensory axons and sympathetic and parasympathetic neurons. note: 'Found by winnow, kev and lev in p006, p005, p007. Claude judged: partial.' - paper: pmid34055418 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The association between POTS and JHS can be explained by predominant peripheral neuropathy in the autonomous system and a failure of the peripheral vascular system to maintain resistance in areas exposed to stress due to orthostasis, blood stasis in the lower limbs, or pathologies of the central nervous system [11]. The result is a functional decrease in blood volume with compensation given by increased heart rate and myocardia contractility. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Discussion quote: Patient's with postural tachycardia syndrome have peripheral autonomic dysfunction. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid33316414 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Discussion quote: Much of the evidence in literature indicates that POTS may be a restricted autonomic neuropathy and our findings may support this conclusion. note: 'Found by winnow, kev and lev in p034. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p004, p031, p033. Claude judged: partial.' - paper: pmid29876157 cited: true text: full license: by verdict: partial section: Review quote: Patients with this syndrome have a partial neuropathic state with impaired lower extremity sympathetic innervation, abnormal venous pooling, and hypovolemic state with low renin–angiotensin–aldosterone system upregulation [24]. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid19687022 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19687022. Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid11198483 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11198483. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - postinfectious_evidence - proposed_mechanism_of - pots papers: 66 evidence: - paper: pmid42512077 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Among proposed etiologies for POTS, Epstein–Barr virus and other pathogens have been identified as potential initiating events; frequently, patients report a history of mononucleosis prior to development of debilitating symptoms [24]. note: 'Found by winnow, kev and lev in p006, p036. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Discussion quote: Besides small fiber neuropathy, proposed POTS mechanisms include immune-mediated inflammation triggered by autoantigens or persistent viral particles [11, 20]. The short latency between infection and symptoms onset observed in most cases indicates a direct immune-mediated process, and the stronger immune responsiveness of younger individuals may predispose them to POTS development both after COVID-19 infection and vaccination. note: 'Found by winnow, kev and lev in p047, p037. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: Abstract > Introduction quote: The etiology of POTS has not been entirely defined, but researchers have speculated that an immunological stressor such as a viral infection might be an initiating event. note: 'Found by winnow, kev and lev in p007, p001, p006. Claude judged: supports.' - paper: pmid40977456 cited: true text: full license: by-nc verdict: supports section: Body quote: However, in our discussion, we specifically addressed the potential role of viral infections and autoimmune mechanisms in the development of POTS. note: 'Found by winnow, kev and lev in p008, p010, p015. Claude judged: supports.' - paper: pmid40763323 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Increased viral exposure may have triggered autoimmune mechanisms that contribute to the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p024, p006. Claude judged: supports.' - paper: pmid39857750 cited: true text: full license: by verdict: supports section: 2. POTS, Long COVID and the CNS quote: Pre-pandemic, POTS was known to occur after a viral or bacterial infection in at least 40% of patients and was thought to be of heterogeneous and complex pathophysiology involving central and peripheral autonomic nervous system networks, small fiber neuropathy, cerebral hypoperfusion, mast cell hyperactivity and autoimmunity [9,10,11]. note: 'Found by winnow, kev and lev in p005, p008, p011. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > COVID-19 Infection and Post-viral Postural Orthostatic Tachycardia Syndrome quote: Even though an exact mechanism has not been identified, it is suggested that autoimmune responses to viral illness may trigger POTS, with up to 50% of POTS patients reporting a viral illness preceding their symptoms.[22] note: 'Found by winnow, kev and lev in p011, p032. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: Abstract quote: The underlying causes of POTS following COVID-19 remain unknown, with various theories proposed such as renin–angiotensin–aldosterone system (RAAS) dysregulation, hyperadrenergic reaction, and direct viral infection. note: 'Found by winnow, kev and lev in p001, p009, p027. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: The onset of POTS is frequently linked to triggers, such as long COVID-19, the human papillomavirus (HPV) vaccine, infections, or trauma, which can subsequently lead to immunological changes. note: 'Found by winnow, kev and lev in p014, p020. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: The underlying cause of dysautonomia post-COVID-19 infection is not well understood. However, a viral infection by SARS-CoV-2 triggering autoimmune response and direct neurotoxic effects has been suggested as an underlying cause for developing post-COVID-19 POTS [57,58]. note: 'Found by winnow, kev and lev in p027, p006. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Dysautonomia and small-fiber neuropathy often occur as a complication of certain infections quote: Approximately half of patients with POTS report symptoms of a preceding infection (3). Infectious causes of POTS include EBV, herpes viruses, flavivirus, enterovirus 71, retroviruses (HIV), and SARS-CoV-2 (7). note: 'Found by winnow, kev and lev in p003, p002, p007. Claude judged: supports.' - paper: pmid38240001 cited: true text: full license: by verdict: supports section: DISCUSSION quote: "Particularly, the production of adrenergic autoantibodies is believed to be an important factor in postinfection\ \ POTS.\n30\n Originally, approximately 40% of POTS cases are reported to occur after some infectious diseases." note: 'Found by winnow, kev and lev in p026, p009. Claude judged: supports.' - paper: pmid37822957 cited: true text: full license: by verdict: supports section: Introduction quote: Up to 50% of patients with POTS describe a viral infection as the trigger of their symptoms. note: 'Found by winnow, kev and lev in p005, p024. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 3. Etiopathogenic basis quote: The pathophysiological mechanisms resulting in autonomic dysfunction in POTS may include sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac sympathoexcitation response (hyperadrenergic POTS) with increased serum norepinephrine, volume dysregulation (hypovolemia), baroreceptor dysfunction, peripheral neuropathy, and autoimmunity due to molecular mimicry following infections by pathogens such as Epstein–Barr virus, cytomegalovirus, or Borrelia Burgdorferi (1, 15). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Abstract quote: It is considered a relatively rare condition that affects approximately 0.2% of the general population, and it is estimated that between 500,000 to 1,000,000 individuals in the United States have the condition and recently has been linked to post-infectious (viral) etiologies. note: 'Found by winnow, kev and lev in p005, p006, p001. Claude judged: supports.' - paper: pmid37209261 cited: true text: full license: none verdict: supports section: Introduction > Mechanisms of Cardiac Damage quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37209261. Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response. note: 'Found by winnow, kev and lev in p012, p001, p017. Claude judged: supports.' - paper: pmid36947108 cited: true text: full license: none verdict: supports section: Dysautonomia in PASC > What do we know about autonomic dysfunction in PASC? quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: More recently, dysautonomia has been observed in patients with coronavirus disease 2019 (COVID-19), and POTS has been identified as a possible long-term manifestation of COVID-19. It has also been found that the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor, possibly causing hyperadrenergic POTS [3]. note: 'Found by winnow, kev and lev in p001, p003, p015. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Discussion quote: Several conditions, including infection, surgery, and pregnancy, can precipitate or even exacerbate POTS. The chief etiology is usually post-infection, which has been reported with COVID-19. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid36732397 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p006, p007. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Discussion quote: It is postulated that the cytokine storm from COVID-19 results in sympathetic dysregulation, causing an abnormal autonomic response in POTS.7 The relationship between heart rate variability due to this autonomic failure and inflammatory factors from infection has been well studied.7 note: 'Found by winnow, kev and lev in p023, p002, p011. Claude judged: supports.' - paper: pmid36414707 cited: true text: full license: by verdict: supports section: Discussion > Proinflammatory state in POTS quote: Growing evidence points toward POTS being an autoimmune disease, oftentimes triggered by a viral or bacterial infection28. note: 'Found by winnow, kev and lev in p024, p002. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p014, p017. Claude judged: supports.' - paper: pmid35725868 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid35680184 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35680184. Found by winnow, kev and lev in p002, p004. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What is the pathophysiology of POTS? quote: Postural orthostatic tachycardia syndrome may have an immunological cause. Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid35269395 cited: true text: full license: by verdict: supports section: 1. Introduction quote: With associations of viral infections as a potential etiology of POTS and evidence that many COVID-19 long haulers are developing POTS, platelets may also play a significant role in the etiology or perpetuation of the disorder. note: 'Found by winnow, kev and lev in p003, p002, p017. Claude judged: supports.' - paper: pmid35181863 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35181863. Found by winnow, kev and lev in p005, p001, p002. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Infections are known triggers of dysautonomia, particularly in POTS. note: 'Found by winnow, kev and lev in p008, p017, p022. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Putative Mechanisms for Symptomatic Tachycardia in Post-COVID-19 Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid34265539 cited: true text: full license: none verdict: supports section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Immune-mediated mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p021, p001. Claude judged: supports.' - paper: pmid34127505 cited: true text: full license: none verdict: supports section: Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34127505. Found by winnow, kev and lev in p003, p015, p019. Claude judged: supports.' - paper: pmid33983522 cited: true text: full license: none verdict: supports section: 'Part II: Resolved Infection > Long COVID' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33983522. Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Discussion quote: It is postulated that disruption of the body’s autonomic nervous system in POTS has potential triggers from viral infections and vaccines. note: 'Found by winnow, kev and lev in p008, p010. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Diskussion quote: Am Fallbeispiel 2 können wir zeigen, dass Kinder nach SARS-CoV-Infektion eine chronische Regulationsstörung des autonomen Nervensystems mit einem POTS entwickeln können, welches in einem einfachen aktiven Stehtest mit kontinuierlicher EKG-Registrierung nachweisbar ist. note: 'Found by winnow, kev and lev in p001, p007, p010. Claude judged: supports.' - paper: pmid33927679 cited: true text: full license: by verdict: supports section: Discussion quote: While not definitively established to this point, it has been generally assumed that the development of autonomic nervous system impairment in POTS patients is a para- or post-infectious, immune-mediated process. note: 'Found by winnow, kev and lev in p013, p006. Claude judged: supports.' - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p040, p023, p039. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: INTRODUCTION quote: The syndrome has been postulated to have post-viral autoimmune activation as a possible etiology (3). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid33562074 cited: true text: full license: by verdict: supports section: 3. Results > 3.3. Biomarkers of Inflammation quote: A significant number of our patients have described Epstein Barr virus infections and gastrointestinal pain that could be related to an enteric viral infection preceding the onset of symptoms and ultimately the development of POTS. note: 'Found by winnow, kev and lev in p032, p001, p003. Claude judged: supports.' - paper: pmid33316414 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p013, p011. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Discussion quote: Usually, patients will report the occurrence of a triggering event weeks to months before the onset of POTS symptoms.5–7 These triggering events may include a viral illness, trauma, pregnancy, electrical or lighting injury, or bariatric surgery. note: 'Found by winnow, kev and lev in p011, p010, p013. Claude judged: supports.' - paper: pmid32848537 cited: true text: full license: by verdict: supports section: Discussion quote: The autoimmune hypothesis of POTS etiology could be a link between immune triggers, such as viral and bacterial infections, or vaccinations, as patients often identify a triggering factor with the beginning of symptoms. note: 'Found by winnow, kev and lev in p037, p039. Claude judged: supports.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: One might postulate that a viral infection could stimulate molecular mimicry and that the A1 receptor might have stoichiometry similar to an unknown antigenic epitope in infection and/or inflammation. A significant number of our patients have described Epstein–Barr virus infections and gastrointestinal pain that could be related to an enteric viral infection preceding the onset of symptoms and ultimately the development of POTS and its diagnosis. note: 'Found by winnow, kev and lev in p025, p002. Claude judged: supports.' - paper: pmid31001074 cited: true text: full license: by verdict: supports section: Introduction quote: It has been observed that some patients develop POTS after experiencing a febrile illness, presumably viral (Grubb, 2008; Li et al., 2014). This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al., 2015; Watari et al., 2018) support this hypothesis. note: 'Found by winnow, kev and lev in p005, p027. Claude judged: supports.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: supports section: Introduction quote: The etiology of POTS is unknown although several pathophysiological mechanisms have been proposed.(2006) Some subjects report a “viral‐like” illness 2 to 6 months prior to the onset of symptoms, thus supporting the hypothesis that an autoimmune‐mediated molecular mimicry might be present. note: 'Found by winnow, kev and lev in p001, p004, p025. Claude judged: supports.' - paper: pmid23002038 cited: true text: full license: none verdict: supports section: 4 Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23002038. Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid20035362 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p004, p025. Claude judged: supports.' - paper: pmid19058765 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid42524295 cited: true text: full license: by verdict: partial section: Discussion quote: On the other hand, several viral infections have been associated with brainstem dysfunction and the development of POTS-like symptoms (69, 70). note: 'Found by winnow, kev and lev in p089, p007. Claude judged: partial.' - paper: pmid42245008 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42245008. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid41767063 cited: true text: full license: by verdict: partial section: Background quote: Notably, this is the first report to systematically incorporate HRV and SSR assessments, and explicitly identify infection as a precipitating factor. note: 'Found by winnow, kev and lev in p006, p027. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: The study will investigate whether other immune mechanisms play a role in contributing to post-COVID-19 POTS. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Hyperadrenergic states from infection, hypovolemia, and deconditioning are implicated in development of orthostatic intolerance post-pandemic. In a retrospective review of 20 patients, 75% had postural tachycardia, with residual dysfunction noted 6–8 months post infection [6]. note: 'Found by winnow, kev and lev in p010, p027, p029. Claude judged: partial.' - paper: pmid36614874 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Since the beginning of the pandemic, there have been several published case reports of postural orthostatic tachycardia syndrome (POTS) among patients with long-lasting symptoms after complete recovery from COVID-19 infection [7,8,9,10,11]. note: 'Found by winnow, kev and lev in p003, p021. Claude judged: partial.' - paper: pmid35852546 cited: true text: full license: none verdict: partial section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Spezifität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p025, p030. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Neurotropism quote: Secondly, a suggested and more direct cause of POTS could be related to the spread of COVID-19 to the central nervous system (CNS) by neural propagation, causing direct damage on nerves or indirect damage via a cytokine storm (28). note: 'Found by winnow, kev and lev in p008, p009, p006. Claude judged: partial.' - paper: pmid35118574 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35118574. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid34992725 cited: true text: full license: by verdict: partial section: Key Points quote: Inappropriate sinus tachycardia and postural orthostatic tachycardia syndrome seem to be common in the convalescent period of COVID-19 infection as a result of post-infectious dysautonomia. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Discussion quote: The mechanism of post-COVID POTS remains unknown, although inflammatory and autoimmune responses, including the generation of autoantibodies, may be at play [6]. It is postulated that the cytokine storm from the COVID-19 infection results in sympathetic dysregulation, causing the abnormal autonomic response in POTS [6]. note: 'Found by winnow, kev and lev in p009, p001. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.6 Immune-Mediated quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Its onset may follow an acute infection or vaccination but more commonly appears without antecedent causative events.2,6 note: 'Found by winnow, kev and lev in p028, p004. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Autoimmune/Autoantibodies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p031. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: The cholinergic POTS subgroup is therefore consistent with the hypothesis that neuropathic POTS is a restricted autonomic neuropathy [6]. Post-ganglionic cholinergic dysautonomia is frequently associated with a viral infection and is most likely immune-mediated [6,39-45]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - edge: - deconditioning_evidence - proposed_mechanism_of - pots papers: 40 evidence: - paper: pmid42037722 cited: true text: full license: by verdict: supports section: Introduction quote: Despite consistent diagnostic criteria, POTS is mechanistically heterogeneous. Major reviews emphasize roles for hypovolemia, venous pooling, deconditioning, peripheral autonomic neuropathy, hyperadrenergic states, and immune-mediated mechanisms. note: 'Found by winnow, kev and lev in p001, p017, p007. Claude judged: supports.' - paper: pmid41976810 cited: true text: full license: by verdict: supports section: 1. Introduction quote: 'Sheldon et al. [6] summarise two possible mechanisms for PoTS: firstly, autonomic denervation leading to impaired peripheral venoconstriction, which leads to venous pooling, hypovolaemia, and hyperadrenergic stimulation with raised plasma norepinephrine levels, or, secondly, deconditioning, which may be compounded by anxiety and hypervigilance secondary to the underlying physiological abnormalities.' note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: Studies have shown that bed rest or deconditioning can contribute independently to the development of POTS, regardless of the underlying mechanism [5]. Longer periods of physical inactivity can lead to cardiac muscular atrophy, reduction in stroke volume and overall hypovolemia [14]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid41166031 cited: true text: full license: by verdict: supports section: Introduction quote: While the first studies of exercise in POTS framed it as countering deconditioning, there has since been significant debate as to whether deconditioning is a primary cause of POTS or is more likely to occur secondary to the disorder [3]. note: 'Found by winnow, kev and lev in p005, p006, p028. Claude judged: supports.' - paper: pmid40763323 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Postural Orthostatic Tachycardia Syndrome is particularly prevalent during childhood and adolescence, and its pathophysiology involves a complex interplay of autonomic dysfunction, immune system factors, and physical deconditioning.2 note: 'Found by winnow, kev and lev in p026, p005. Claude judged: supports.' - paper: pmid40538940 cited: true text: full license: by verdict: supports section: Introduction quote: Deconditioning is also considered to be the final pathway in the pathogenesis of PoTS, as well as a factor involved in its pathogenesis (12–14, 16–19). note: 'Found by winnow, kev and lev in p007, p008, p030. Claude judged: supports.' - paper: pmid39678714 cited: true text: full license: by-nc verdict: supports section: Results quote: According to the study, it was found that POTS may be a result of deconditioning, and that a carefully prescribed exercise training program can be an effective non-drug therapy option for patients with POTS. note: 'Found by winnow, kev and lev in p034, p026, p041. Claude judged: supports.' - paper: pmid39597891 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Several possible pathophysiologic mechanisms were proposed in the early 1990s when POTS was first described. Cardiac deconditioning was among these, when it was observed that patients with POTS were performing at a lower level of cardiac performance due to reduced stroke volume and VO2 max than their healthy counterparts [4]. note: 'Found by winnow, kev and lev in p005, p006, p009. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Cardiovascular deconditioning may be implicated in POTS via cardiac atrophy and hypovolemia causing reactive tachycardia.[9] note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid36387679 cited: true text: full license: by-nc-sa verdict: supports section: Introduction quote: The multiple factors like moderate autonomic dysfunction, increased sympathetic tone, inadequate venous return or excessive blood venous pooling, and severe deconditioning may be responsible for POTS symptoms.[1] note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: The pathophysiology of POTS remains unknown, however there is a number of physiological mechanisms that have been supposed to be involved. These may include sympathetic dysregulation, hypovolemia, hyperadrenergic stimulation, deconditioning12,57, autoantibody mediated response57, and mast cell activation58,59. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid36043022 cited: true text: full license: by verdict: supports section: Discussion quote: However, recent studies suggest cardiac deconditioning, increased sensitivity to beta-adrenoreceptors, and neuropathy in the distal vessels are also responsible for POTS. note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p014, p017, p002. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Hypovolaemia quote: Firstly, it has been suggested that POTS occurs due to decreased blood volume and deconditioning of the heart, which subsequently increases cardiac sympathetic nervous system (SNS) output (24, 32, 33). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid34987818 cited: true text: full license: by-nc verdict: supports section: Discussion quote: There are various pathophysiological mechanisms for developing OI in POTS. One mechanism broadly described is cardiovascular deconditioning following prolonged bed rest, resulting in cardiac atrophy, and subsequent physical deconditioning. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid34331416 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34331416. Found by winnow, kev and lev in p013, p003. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid32848537 cited: true text: full license: by verdict: supports section: Introduction quote: The cause of POTS has not yet been established (Benarroch, 2012), though many possible disease mechanisms including autonomic denervation (Kimpinski et al., 2012; Haensch et al., 2014), autonomic autoimmunity (Ruzieh et al., 2017), hypovolemia (Benarroch, 2012; Kimpinski et al., 2012), hyperadrenergic stimulation (Kimpinski et al., 2012), and deconditioning have been proposed (Benarroch, 2012; Fu and Levine, 2015). note: 'Found by winnow, kev and lev in p035, p008. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Mechanisms and symptoms quote: Autonomic nervous system dysfunction,2 increased sympathetic tone,3 and physical deconditioning4,5 are some of the suggested contributory factors. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid32321428 cited: true text: full license: by verdict: supports section: Background quote: Beyond genetic norepinephrine transporter deficiency, several theories have been proposed for the syndrome’s etiology, including antiadrenergic autoimmunity [2–4], baroreflex dysfunction [5], deconditioning [6], abnormal mast cell activation [1], excessive sympathetic drive and/or sympathetic denervation [7]. note: 'Found by winnow, kev and lev in p004, p005, p031. Claude judged: supports.' - paper: pmid32222376 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32222376. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid31798399 cited: true text: full license: by verdict: supports section: Introduction > Orthostatic Cardiovascular Responses Are Impaired in Patients With Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: Lastly, physical deconditioning of the heart due to conditions such as viral infections or chronic fatigue has also been recognized as a possible mechanism underlying POTS (Fu et al., 2010). There is an association between POTS and cardiac deconditioning, and this is thought to be the result of a decreased heart size and associated decrease in cardiac output (Fu et al., 2010). note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p002, p003, p001. Claude judged: supports.' - paper: pmid25487551 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25487551. Found by winnow, kev and lev in p002, p003, p005. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p059. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: 'The etiology of POTS is probably heterogeneous and the pathophysiology remains unclear. Three main groups have been identified: neuropathic, hyperadrenergic and POTS related to deconditioning [1].' note: 'Found by winnow, kev and lev in p016, p018. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p007, p009, p035. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p003, p004, p020. Claude judged: supports.' - paper: pmid18704621 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 18704621. Found by winnow, kev and lev in p001, p011, p014. Claude judged: supports.' - paper: pmid39297132 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: However, the role of venous or splanchnic pooling, alterations of peripheral venous hemodynamics, impaired blood volume regulation (relative central hypovolemia), absolute hypovolemia, peripheral small fiber neuropathy, and cardiovascular deconditioning as potential mechanisms of reduced stroke volume, brain hypoperfusion, and, in turn, postural ventilation have to be explored.1 note: 'Found by winnow, kev and lev in p004, p005. Claude judged: partial.' - paper: pmid35647216 cited: true text: full license: by-nc verdict: partial section: Discussion quote: 'Physical deconditioning may contribute to post-concussive OT, as it is common after concussion and known to contribute to OI.' note: 'Found by winnow, kev and lev in p028, p035. Claude judged: partial.' - paper: pmid35557616 cited: true text: full license: by verdict: partial section: Discussion quote: In the case that we presented and in our retrospective cohort, both the symptoms from PANS and POTS often lead to inactivity and deconditioning, and this deconditioning may further contribute to POTS. note: 'Found by winnow, kev and lev in p034. Claude judged: partial.' - paper: pmid34265539 cited: true text: full license: none verdict: partial section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p030, p028. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Introduction quote: The multiple factors like moderate autonomic dysfunction, increased sympathetic tone, inadequate venous return or excessive blood venous pooling, and severe deconditioning may be responsible for POTS symptoms. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid33316414 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms of post-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33316414. Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Introduction quote: One must also rule out secondary causes of POTS due to circulatory insufficiency as seen with dehydration and physical de-conditioning after inanition and prolonged bed rest. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: partial section: Introduction quote: The pathophysiology underlying POTS remains incompletely understood, is likely to be multifactorial and varies in different subgroups of POTS patients. Factors such as moderate autonomic dysfunction, increased sympathetic tone, severe deconditioning, inadequate venous return or excessive blood venous pooling may contribute to POTS symptoms.2 note: 'Found by winnow, kev and lev in p003, p010. Claude judged: partial.' - paper: pmid25168872 cited: true text: full license: by verdict: partial section: Introduction quote: Observations such as these prompt speculation that POTS is akin to a deconditioned state (Joyner and Masuki 2008; Lewis et al. 2013). note: 'Found by winnow, kev and lev in p004, p005, p019. Claude judged: partial.' - paper: pmid21906029 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: Nonetheless, we cannot rule out that milder forms of cardiovascular deconditioning may contribute to the abnormalities observed in POTS [8,35,38]. note: 'Found by winnow, kev and lev in p032. Claude judged: partial.' - paper: pmid21690484 cited: true text: full license: none verdict: partial section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21690484. Found by winnow, kev and lev in p003, p024, p032. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - pots papers: 39 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Results > Newly diagnosed CAD following COVID-19 infection and vaccination quote: Following COVID-19 infection, 22 individuals were newly diagnosed with POTS, 12 with VVS, and 1 with delayed and 1 with transient OH, whereas in 39 cases presenting with new-onset OI the diagnostic workup excluded any CAD (i.e., OIw/oCAD). In most newly diagnosed CAD, the causal association with the passed COVID-19 infection was deemed probable (34 out of 36, 94%). note: 'Found by winnow, kev and lev in p048, p022, p037. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 1 Introduction quote: A direct link to the development of POTS as a sequela of COVID-19 infection in PASC gives great credence to the idea that the etiology of POTS involves an immunologic stressor such as a preceding viral illness. note: 'Found by winnow, kev and lev in p007, p001, p006. Claude judged: supports.' - paper: pmid39597891 cited: true text: full license: by verdict: supports section: 1. Introduction quote: An estimated 3 million people in the United States had POTS before the COVID-19 pandemic, but the prevalence is now significantly higher and has likely at least doubled, due, in part, to POTS that can follow SARS-CoV-2 infection as part of Long COVID [1]. note: 'Found by winnow, kev and lev in p003, p006, p011. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: Abstract quote: In recent studies, a considerable number of individuals recovering from COVID-19 have been reported to experience POTS within 6 to 8 months post-infection. note: 'Found by winnow, kev and lev in p015, p027, p001. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Long COVID-19 triggers an extended inflammatory response, characterized by the continuous production of cytokines and other inflammatory mediators [61]. This prolonged state of inflammation can lead to systemic effects, including damage to the vascular endothelium [62] and dysregulation of the ANS [63], creating fertile ground for the development of conditions such as POTS. note: 'Found by winnow, kev and lev in p020, p014. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Not only does contracting SARS-CoV-2 infection confer the possibility of developing long COVID and subsequent development of POTS, but recipients of the SARS-CoV-2 vaccine have also been shown to develop POTS at a higher rate. note: 'Found by winnow, kev and lev in p027, p029. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Introduction quote: Recently, several case reports showed an increasing incidence of POTS as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients who had chronic signs and symptoms of the infection (long COVID (coronavirus disease)). note: 'Found by winnow, kev and lev in p005, p001, p002. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports quote: The earliest reports of a POTS-like syndrome in the aftermath of COVID-19 infection emerged in March 2020.37 Since then, there has been growing awareness of a potential link between COVID infections and more recently vaccines and POTS. note: 'Found by winnow, kev and lev in p005, p015, p021. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: Post-COVID Conditions (PCC) encompass a variety of sequelae or health conditions that last four weeks or more after a SARS-CoV-2 infection [30]. Although it can affect many different body systems, it can ultimately cause autonomic dysfunction, which can lead to postural orthostatic tachycardia syndrome (POTS) [30]. note: 'Found by winnow, kev and lev in p012, p001, p016. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: More recently, dysautonomia has been observed in patients with coronavirus disease 2019 (COVID-19), and POTS has been identified as a possible long-term manifestation of COVID-19. It has also been found that the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor, possibly causing hyperadrenergic POTS [3]. note: 'Found by winnow, kev and lev in p001, p003, p015. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Recently, POTS has been identified in ∼20% of cases of PASC, in which symptoms persist >4 weeks after the onset of COVID-19 illness.5,6 It is postulated that the cytokine storm from COVID-19 results in sympathetic dysregulation, causing an abnormal autonomic response in POTS.7 note: 'Found by winnow, kev and lev in p023, p002, p011. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Results > Post COVID-19 postural orthostatic tachycardia syndrome quote: Viral infection is the most commonly reported and has been shown to trigger POTS in 28–41% of patients19. Various infectious pathogens have been suggested to be associated with the onset of POTS, including the Epstein Barr virus25–27, upper respiratory infections, gastroenteritis and recently SARS-CoV217,28,29. note: 'Found by winnow, kev and lev in p001, p007, p010. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p015, p016. Claude judged: supports.' - paper: pmid35852546 cited: true text: full license: none verdict: supports section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Plausibilität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Inflammation and Autoimmunity quote: COVID-19 infection can cause a cytokine storm and inflammation that could trigger chronic neuronal dysregulation (47). One mechanism could be via the development of autoantibodies which cross-react with autonomic ganglia as part of acute and long-term COVID-19 infection, and lead to dysautonomia and POTS. note: 'Found by winnow, kev and lev in p008, p009, p006. Claude judged: supports.' - paper: pmid35269395 cited: true text: full license: by verdict: supports section: 1. Introduction quote: With associations of viral infections as a potential etiology of POTS and evidence that many COVID-19 long haulers are developing POTS, platelets may also play a significant role in the etiology or perpetuation of the disorder. note: 'Found by winnow, kev and lev in p003, p002. Claude judged: supports.' - paper: pmid34992725 cited: true text: full license: by verdict: supports section: Key Points quote: Inappropriate sinus tachycardia and postural orthostatic tachycardia syndrome seem to be common in the convalescent period of COVID-19 infection as a result of post-infectious dysautonomia. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid34729276 cited: true text: full license: by verdict: supports section: Discussion quote: The mechanism of post-COVID POTS remains unknown, although inflammatory and autoimmune responses, including the generation of autoantibodies, may be at play [6]. It is postulated that the cytokine storm from the COVID-19 infection results in sympathetic dysregulation, causing the abnormal autonomic response in POTS [6]. note: 'Found by winnow, kev and lev in p001, p009. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Diskussion quote: Am Fallbeispiel 2 können wir zeigen, dass Kinder nach SARS-CoV-Infektion eine chronische Regulationsstörung des autonomen Nervensystems mit einem POTS entwickeln können, welches in einem einfachen aktiven Stehtest mit kontinuierlicher EKG-Registrierung nachweisbar ist. note: 'Found by winnow, kev and lev in p001, p007, p010. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Conclusion quote: Autonomic dysfunction presenting as POTS can be a delayed manifestation of COVID-19 infection. note: 'Found by winnow, kev and lev in p011, p013. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Review quote: Researchers speculate that fibrinaloid microclots seen in POTS, particularly long-COVID-associated POTS, may lead to microcapillary obstruction and local tissue hypoxia. note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid42512077 cited: true text: full license: by verdict: partial section: 5. Conclusions quote: This investigation highlights a distinct, shared cytokine profile in POTS and Long COVID-associated POTS, consistent with an active innate immune system. These findings suggest an immunological relationship between primary viral insult and chronic dysautonomia, suggesting that clinical successes in Long COVID research may be applicable to the broader POTS population. note: 'Found by winnow, kev and lev in p033, p036. Claude judged: partial.' - paper: pmid42245008 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42245008. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Immunologic mechanisms discussed in the literature include persistent immune activation, T-cell/NK cell exhaustion, and development of autoantibodies (10–14). The study will investigate whether other immune mechanisms play a role in contributing to post-COVID-19 POTS. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: The growing number of individuals experiencing OI and POTS after COVID-19 raises important questions about the relationship between viral infections, vaccination, and the onset of autonomic dysfunction. note: 'Found by winnow, kev and lev in p031, p033. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > COVID-19 Infection and Post-viral Postural Orthostatic Tachycardia Syndrome quote: Long COVID may be implicated in similar mechanisms related to POTS, including neuropathologies, endothelial dysfunction, and blood flow abnormalities.[42] note: 'Found by winnow, kev and lev in p032. Claude judged: partial.' - paper: pmid39076856 cited: true text: full license: by verdict: partial section: 5. Symptoms and Pathologic Findings of Cardiovascular Disease in Post-Acute COVID-19 Syndrome > 5.2 Pathologic Findings > 5.2.4 Postural Orthostatic Tachycardia Syndrome (POTS) quote: "Hypothetically, POTS is caused by autonomic dysfunction in long COVID patients \n[138]. Autonomic dysfunction\ \ in long COVID is provoked by the hyperadrenergic \nstate and the resetting of baroreceptor control, which\ \ is stimulated by \nangiotensin II upregulation." note: 'Found by winnow, kev and lev in p043. Claude judged: partial.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient. note: 'Found by winnow, kev and lev in p001, p018. Claude judged: partial.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 7. The Role of Fibrinaloid Microclots in POTS quote: Other mechanisms for POTS in long COVID may include:Relative hypovolemia secondary to inadequate peripheral vasoconstriction. note: 'Found by winnow, kev and lev in p001, p016, p005. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Recently, there was a surge in the incidence of POTS after the COVID-19 pandemic. Functional antibodies against different GPCRs have also been demonstrated in the serum of symptomatic post-COVID-19 patients.[23] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid37670400 cited: true text: full license: by verdict: partial section: Introduction quote: Positional tachycardia and chronic orthostatic intolerance symptoms in PACS mimic Postural Orthostatic Tachycardia Syndrome [POTS] [22, 23], a condition that is associated with autonomic nervous system dysfunction and that can be triggered after an acute viral illness [24–27]. note: 'Found by winnow, kev and lev in p004, p007. Claude judged: partial.' - paper: pmid36947108 cited: true text: full license: none verdict: partial section: Commonalities with ME/CFS and other post-infection syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: partial.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: •POTS, neurally-mediated syncope from low-volume states maybe observed post-COVID-19. note: 'Found by winnow, kev and lev in p027, p009, p029. Claude judged: partial.' - paper: pmid36614874 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Since the beginning of the pandemic, there have been several published case reports of postural orthostatic tachycardia syndrome (POTS) among patients with long-lasting symptoms after complete recovery from COVID-19 infection [7,8,9,10,11]. note: 'Found by winnow, kev and lev in p003, p021. Claude judged: partial.' - paper: pmid35725868 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What is the pathophysiology of POTS? quote: Recently, numerous cases of POTS33 and other forms of sinus tachycardia (e.g., inappropriate sinus tachycardia)34 after a SARS-CoV-2 infection have been reported. Good data on the frequency of POTS among patients with long-term complications from COVID-19 (“long COVID syndrome”) are lacking. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 3. COVID-19 Infection and Dysautonomia quote: A growing body of evidence links PASC to CVAD, with a number of reports suggesting the possibility of previously infected COVID-19 patients experiencing symptoms suggestive of POTS [10,13,16,43,44,45,46]. note: 'Found by winnow, kev and lev in p025, p008, p017. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p040. Claude judged: partial.' - paper: pmid32970212 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32970212. Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - proposed_mechanism_of - pots papers: 28 evidence: - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Cerebral Hypoperfusion quote: Cerebral hypoperfusion emerged as one of the major mechanisms of POTS, dysautonomia, myalgic encephalomyelitis/chronic fatigue syndrome and probably Long COVID.49,50 Cerebral and brainstem hypoperfusion together with neuroinflammation, specifically at the dorsolateral medulla, may be the CNS mechanisms in POTS and Long COVID and need to be investigated further.22,51,52 note: 'Found by winnow, kev and lev in p016, p002, p018. Claude judged: supports.' - paper: pmid41103515 cited: true text: full license: by verdict: supports section: Differential diagnosis of OD with PPPD > Hemodynamic orthostatic dizziness > Postural orthostatic tachycardia syndrome quote: Abnormal cerebral blood flow (CBF) is central to POTS pathophysiology, with findings indicating reduced cerebral perfusion, impaired autoregulation, and oscillatory CBF associated with cognitive dysfunction. note: 'Found by winnow, kev and lev in p010, p055. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: Abstract quote: Our findings demonstrate that an insufficient cerebral blood supply, driven by hypovolemia and impaired vascular compliance, combined with autonomic dysregulation, underlies the hallmark tachycardia in Postural Orthostatic Tachycardia Syndrome. note: 'Found by winnow, kev and lev in p001, p047, p050. Claude judged: supports.' - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: supports section: CBF in OI > CBF in POTS quote: Furthermore, Stewart et al demonstrated that the drop in CBv with head‐up tilt in POTS occurs before orthostatic tachycardia and hyperpnea, which suggests that CBv may be driving POTS pathophysiology. note: 'Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid39857750 cited: true text: full license: by verdict: supports section: '3. Dorsolateral Medulla: Localization for POTS and Long COVID' quote: Cerebral hypoperfusion is one of the major mechanisms of POTS, autonomic dysfunction, myalgic encephalomyelitis/chronic fatigue syndrome and probably Long COVID [6]. note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid39597891 cited: true text: full license: by verdict: supports section: '2. POTS and Exercise: What Is Known' quote: Although cardiovascular deconditioning has been considered to be the cause or a major mechanism of POTS, emerging evidence suggests that this is not the case and that POTS involves various mechanisms, including cerebral hypoperfusion and possible neuroinflammation [7,11]. note: 'Found by winnow, kev and lev in p005, p010. Claude judged: supports.' - paper: pmid39544990 cited: true text: full license: by verdict: supports section: Conclusion quote: Our findings support the hypothesis that HYCH and POTS represent a spectrum of the same disorder of cerebral hypoperfusion. Reduced cerebral blood flow due to venous pooling and related hypocapnia may be a physiological substrate. note: 'Found by winnow, kev and lev in p050, p036, p037. Claude judged: supports.' - paper: pmid39297132 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: In conclusion, the study by Baker et al4 provides valuable insights into the pathophysiology of POTS by showing a possible causal relationship between brain hypoperfusion during orthostatic stress and postural hyperventilation and sympathetic overactivation in POTS. note: 'Found by winnow, kev and lev in p007, p001. Claude judged: supports.' - paper: pmid37443510 cited: true text: full license: by verdict: supports section: 4. Discussion quote: POTS is caused by cerebral hypoperfusion in the brain due to a relative lack of blood volume, thus inducing orthostatic intolerance symptoms. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: 'POTS as a CNS disorder: proposed model' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p017, p026, p027. Claude judged: supports.' - paper: pmid33352894 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Under the hypothesis that POTS is mainly initiated by reduced cerebral blood flow, an earlier study [8] also used transcranial doppler ultrasound (TCD) to investigate the oscillatory CBFV in POTS patients with the relationship of measured arterial pressure, heart rate, CBFV, and PETCO2 to graded changes in tilt angels. note: 'Found by winnow, kev and lev in p001, p008, p003. Claude judged: supports.' - paper: pmid29960989 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Hypocapnic hyperventilation is known to produce tachycardia and symptoms often associated with orthostatic intolerance; therefore, postural hyperventilation causes a form of postural tachycardia syndrome. note: 'Found by winnow, kev and lev in p004, p040. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p005, p026. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Review quote: A brain-based model of cerebral hypoperfusion as a mechanism may help explain brain fog in POTS. note: 'Found by winnow, kev and lev in p052, p001, p007. Claude judged: partial.' - paper: pmid42299168 cited: true text: full license: by verdict: partial section: Review quote: Therefore, neurovascular coupling abnormalities should be described as a cerebral-perfusion pathway that produces multisystem symptom profiles in POTS. note: 'Found by winnow, kev and lev in p035, p033, p034. Claude judged: partial.' - paper: pmid42114076 cited: true text: abstract license: none verdict: partial section: Abstract > Recent Findings quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42114076. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid41740821 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41740821. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid41602336 cited: true text: full license: by verdict: partial section: Discussion quote: While POTS certainly has multifactorial potential causes, in this patient, we propose that it responded to addressing impaired venous blood return to the heart, with resulting diminished cerebral blood flow. note: 'Found by winnow, kev and lev in p022. Claude judged: partial.' - paper: pmid41357159 cited: true text: full license: none verdict: partial section: Discussion > Pulmonary determinants quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p033, p030, p039. Claude judged: partial.' - paper: pmid39297140 cited: true text: full license: by-nc-nd verdict: partial section: Results > Stroke volume and cerebrovascular pulsatility as determinants of postural ventilation and sympathetic activity in patients with POTS quote: Together, these data suggest a role for cerebrovascular pulsatility in the control of ventilation and sympathetic activity and strongly implicate reduced brain perfusion41,42 as a key mechanism underlying exaggerated postural ventilation in patients with POTS. note: 'Found by winnow, kev and lev in p005, p032, p034. Claude judged: partial.' - paper: pmid38490814 cited: true text: full license: by verdict: partial section: INTRODUCTION quote: During a prolonged cognitive stress test, patients with POTS have a greater reduction in cerebral blood velocity that corresponds with a greater symptom score (Wells et al., 2020). Taken together, these data suggest that altered cerebrovascular responsiveness may play a role in symptomology in patients with POTS. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid38390594 cited: true text: full license: by verdict: partial section: Symptoms and clinicopathologic features of dysautonomia quote: It is hypothesized that damage to sympathetic vasomotor nerves impairs the compensatory increase in systemic vascular resistance during orthostatic stress and/or during exercise, resulting in splanchnic and/or lower limb pooling and reduced cerebral blood flow. This results in typical POTS symptoms including dizziness, cognitive dysfunction (colloquially known as “brain fog”), and fatigue. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid37227184 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37227184. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35307584 cited: true text: full license: none verdict: partial section: Discussion > Mechanisms of symptoms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35307584. Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid34746821 cited: true text: full license: by-nc-nd verdict: partial section: Introduction > Carotid body – a unifying hypothesis? quote: This predisposes patients to hypoperfusion of tissues cephalad to the heart, causing stagnant hypoxia from reduced carotid blood flow – a key step causing SNA activation (Marshall, 1994; Prabhakar et al., 2005) in the pathophysiologic cascade in POTS. note: 'Found by winnow, kev and lev in p010, p002. Claude judged: partial.' - paper: pmid25002851 cited: true text: full license: by verdict: partial section: Introduction quote: In these hyperpneic POTS patients, reduced CBF likely compromised CNS function resulting in increased cerebral oxygen demand, neuronal excitability, and continued sympathetic activation (Laffey and Kavanagh, 2002; Del Pozzi et al., 2014). note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid23390443 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Decreased systolic BP during head-up tilt influences cerebral blood perfusion, which explained symptoms of orthostatic intolerance in the symptom-positive group. Ocon et al.20) suggested dynamic cerebral autoregulation is less effective in POTS patients based on a perfectly synchronous correlation between mean arterial pressure and cerebral blood f low velocity. note: 'Found by winnow, kev and lev in p022. Claude judged: partial.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: partial section: Symptoms quote: Patients with POTS experience a variety of symptoms ranging from mild to severe. The most common underlying condition is cerebral hypo-perfusion, which might be due to excessive tachycardia, neurological dysfunction or other idiopathic causes.[5] note: 'Found by winnow, kev and lev in p010, p003. Claude judged: partial.' - edge: - postinfectious_evidence - proposed_mechanism_of - autoimmune_evidence papers: 25 evidence: - paper: pmid40977456 cited: true text: full license: by-nc verdict: supports section: Body quote: Nonetheless, in both the introduction and discussion sections, we emphasized that viral infections such as SARS-CoV-2 may trigger autoimmune and autonomic dysfunction mechanisms. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40692561 cited: true text: full license: by verdict: supports section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Finally, COVID-19 may trigger development of autoantibodies, including antiphospholipid antibodies or antibodies against adrenergic and muscarinic receptors, that could then contribute to the cardiovascular manifestations of LHC (11, 13). note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: However, a viral infection by SARS-CoV-2 triggering autoimmune response and direct neurotoxic effects has been suggested as an underlying cause for developing post-COVID-19 POTS [57,58]. note: 'Found by winnow, kev and lev in p027, p006. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: POTS and other cardiovascular dysautonomias can develop after a SARS-CoV-2 infection. It is thought that these factors might be potent immune triggers that can evoke an autoimmune response in individuals who are susceptible. note: 'Found by winnow, kev and lev in p005, p004, p006. Claude judged: supports.' - paper: pmid36947108 cited: true text: full license: none verdict: supports section: Commonalities with ME/CFS and other post-infection syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Discussion quote: Although post-COVID-19 autonomic pathophysiology is complex and has not been fully elucidated, autoimmunity is thought to be a critical aspect of POTS. Several reports have demonstrated that COVID-19 antibodies cross-react with autonomic nervous system components, such as ganglia, nerve fibers, and G-protein-coupled receptors, which can trigger dysfunction [3,11]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid36732397 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p008, p014. Claude judged: supports.' - paper: pmid35725868 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid34265539 cited: true text: full license: none verdict: supports section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Immune-mediated mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p016, p025. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Diskussion quote: In einem aktuellen Review wird eindrucksvoll gezeigt, dass die SARS-CoV-2-Infektion als potenter Trigger der Bildung von Autoantikörpern angesehen wird [3]. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: supports.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: One might postulate that a viral infection could stimulate molecular mimicry and that the A1 receptor might have stoichiometry similar to an unknown antigenic epitope in infection and/or inflammation. note: 'Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid31001074 cited: true text: full license: by verdict: supports section: Introduction quote: It has been observed that some patients develop POTS after experiencing a febrile illness, presumably viral (Grubb, 2008; Li et al., 2014). This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al., 2015; Watari et al., 2018) support this hypothesis. note: 'Found by winnow, kev and lev in p005, p027. Claude judged: supports.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Some subjects report a “viral‐like” illness 2 to 6 months prior to the onset of symptoms, thus supporting the hypothesis that an autoimmune‐mediated molecular mimicry might be present. note: 'Found by winnow, kev and lev in p001, p004, p025. Claude judged: supports.' - paper: pmid19058765 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: partial section: Discussion quote: Besides small fiber neuropathy, proposed POTS mechanisms include immune-mediated inflammation triggered by autoantigens or persistent viral particles [11, 20]. The short latency between infection and symptoms onset observed in most cases indicates a direct immune-mediated process, and the stronger immune responsiveness of younger individuals may predispose them to POTS development both after COVID-19 infection and vaccination. note: 'Found by winnow, kev and lev in p047. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response.' note: 'Found by winnow, kev and lev in p012, p079. Claude judged: partial.' - paper: pmid36614874 cited: true text: full license: by verdict: partial section: 4. Discussion quote: There are a few possibilities that can explain the post-infectious onset of the symptoms. First, a subset of PASC can be explained by autoimmune inflammation targeted against the autonomic nervous system. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What is the pathophysiology of POTS? quote: Postural orthostatic tachycardia syndrome may have an immunological cause. Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Discussion quote: The mechanism of post-COVID POTS remains unknown, although inflammatory and autoimmune responses, including the generation of autoantibodies, may be at play [6]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Discussion quote: The autoimmune hypothesis of POTS etiology could be a link between immune triggers, such as viral and bacterial infections, or vaccinations, as patients often identify a triggering factor with the beginning of symptoms. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.6 Immune-Mediated quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: Post-ganglionic cholinergic dysautonomia is frequently associated with a viral infection and is most likely immune-mediated [6,39-45]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - edge: - autoimmune_evidence - proposed_mechanism_of - postinfectious_evidence papers: 24 evidence: - paper: pmid38240001 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Particularly, the production of adrenergic autoantibodies is believed to be an important factor in postinfection POTS. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid36614874 cited: true text: full license: by verdict: supports section: 4. Discussion quote: There are a few possibilities that can explain the post-infectious onset of the symptoms. First, a subset of PASC can be explained by autoimmune inflammation targeted against the autonomic nervous system. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Discussion quote: The exact mechanism of post–COVID-19 POTS is unknown and, at best, speculative at this time. Given the lag period of a few weeks between the COVID-19 infection and the onset of POTS symptoms, autoimmunity is a likely mechanism. note: 'Found by winnow, kev and lev in p011, p010. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: partial section: Discussion quote: The short latency between infection and symptoms onset observed in most cases indicates a direct immune-mediated process, and the stronger immune responsiveness of younger individuals may predispose them to POTS development both after COVID-19 infection and vaccination. note: 'Found by winnow, kev and lev in p047. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Finally, COVID-19 may trigger development of autoantibodies, including antiphospholipid antibodies or antibodies against adrenergic and muscarinic receptors, that could then contribute to the cardiovascular manifestations of LHC (11, 13). note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: However, a viral infection by SARS-CoV-2 triggering autoimmune response and direct neurotoxic effects has been suggested as an underlying cause for developing post-COVID-19 POTS [57,58]. note: 'Found by winnow, kev and lev in p027, p006. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid37435242 cited: true text: full license: by verdict: partial section: Discussion quote: An autoimmune basis for a small number of POTS patients has been linked to the observation of orthostatic symptoms following a viral illness [11]. note: 'Found by winnow, kev and lev in p005, p006. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response.' note: 'Found by winnow, kev and lev in p012, p001, p079. Claude judged: partial.' - paper: pmid36947108 cited: true text: full license: none verdict: partial section: Commonalities with ME/CFS and other post-infection syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: partial.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Discussion quote: The chief etiology is usually post-infection, which has been reported with COVID-19. Although post-COVID-19 autonomic pathophysiology is complex and has not been fully elucidated, autoimmunity is thought to be a critical aspect of POTS. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid36732397 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid35853576 cited: true text: full license: none verdict: partial section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p014, p001, p008. Claude judged: partial.' - paper: pmid35852546 cited: true text: full license: none verdict: partial section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Plausibilität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid35725868 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Discussion quote: The mechanism of post-COVID POTS remains unknown, although inflammatory and autoimmune responses, including the generation of autoantibodies, may be at play [6]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid33968543 cited: true text: full license: by verdict: partial section: Discussion quote: Furthermore, it is possible that the anti-SARS-CoV2 antibodies might have an autoimmune basis as they cross-react with the receptors in the ganglia [16]. note: 'Found by winnow, kev and lev in p008, p010. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Diskussion quote: Ursächlich für derartige – oft postinfektiöse – autonome Veränderungen werden Autoantikörper gegen G‑Protein-gekoppelte Rezeptoren angenommen [7], die auch wir bei einigen der von uns untersuchten Kindern mit schweren autonomen Regulationsstörungen nachweisen konnten [2]. note: 'Found by winnow, kev and lev in p011, p012, p001. Claude judged: partial.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: partial section: INTRODUCTION quote: The syndrome has been postulated to have post-viral autoimmune activation as a possible etiology (3). note: 'Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Discussion quote: The autoimmune hypothesis of POTS etiology could be a link between immune triggers, such as viral and bacterial infections, or vaccinations, as patients often identify a triggering factor with the beginning of symptoms. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.6 Immune-Mediated quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: Post-ganglionic cholinergic dysautonomia is frequently associated with a viral infection and is most likely immune-mediated [6,39-45]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - paper: pmid19058765 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - autoimmune_evidence - proposed_mechanism_of - hyperadrenergic_evidence papers: 18 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: We also found that patients with POTS had higher AR autoantibody activity, which may contribute to elevated plasma NE levels and excessive tachycardia. note: 'Found by winnow, kev and lev in p004, p033, p044. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: Pathophysiology of POTS quote: The β-adrenergic autoantibodies may also trigger postural overactivation of the sympathetic nervous system.[15] note: 'Found by winnow, kev and lev in p009, p010, p018. Claude judged: supports.' - paper: pmid37999672 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37999672. Found by winnow, kev and lev in p006, p025, p026. Claude judged: supports.' - paper: pmid37631004 cited: true text: full license: by verdict: supports section: 8. Electroceutical Therapy for Autoimmune Disease > 8.7. Postural Orthostatic Tachycardia Syndrome (POTS) quote: In support of autoimmune-mediated pathways in POTS is the identification in a subgroup of patients expressing serum antiadrenergic autoantibodies capable of exerting direct agonist and allosteric effects that alter receptor function [93]. Consistently, induction of antibodies with similar functional properties in a rabbit experimental model could trigger a hyperadrenergic POTS phenotype [94]. note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid36873318 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Induction of these antibodies with similar functional properties produced a hyperadrenergic POTS phenotype in a rabbit autoimmune model,9 suggesting that the copresence of the 2 sympathomimetic antibodies is capable of causing an excessive increase in adrenergic activity frequently associated with POTS. note: 'Found by winnow, kev and lev in p007, p021, p024. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Discussion quote: Sequelae of these cross-reacting antibodies possibly include interfering with α1-adrenergic receptors leading to a maladaptive vasoconstrictor response and increased sympathetic activation [5]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p009, p011, p030. Claude judged: supports.' - paper: pmid35118574 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35118574. Found by winnow, kev and lev in p006, p029. Claude judged: supports.' - paper: pmid34409582 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34409582. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: In the serum of some patients with POTS, 1 study showed the presence of α1-adrenergic receptor (α1AR) antibodies.7 These antibodies exerted a partial antagonistic effect against the peripheral vasoconstrictive compensation of orthostasis, resulting in an overshooting sympathoneural response to maintain vascular tone. note: 'Found by winnow, kev and lev in p006, p007. Claude judged: supports.' - paper: pmid32743496 cited: true text: full license: by verdict: supports section: Discussion > Adrenergic receptor AAb activity in POTS quote: The α1AR-AAb produce partial antagonism to the α1AR natural ligand NE. This inadequate response to upright posture would lead to baroreceptor-enhanced sympathetic activity. note: 'Found by winnow, kev and lev in p035, p001, p005. Claude judged: supports.' - paper: pmid31547749 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: The differential allosteric effect of α1‐adrenergic receptor and β1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac β1AR. note: 'Found by winnow, kev and lev in p003, p023, p005. Claude judged: supports.' - paper: pmid29682372 cited: true text: full license: by verdict: supports section: 3. Discussion quote: This study entails specific antibodies, such as ganglionic acetylcholine receptor antibody [8] and alpha-1 adrenergic receptor antibody that act as partial antagonists and induce reflex compensatory sympathetic activation [9]. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: supports section: Abstract > Conclusions quote: POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia. note: 'Found by winnow, kev and lev in p003, p006, p026. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: Few of the patients were detected to have autoantibodies to adrenergic, acetylcholine, and angiotensin II receptors [12,15]. These antibodies cause peripheral vasoconstriction to be less effective and eventually cause reflex tachycardia. note: 'Found by winnow, kev and lev in p012, p079. Claude judged: partial.' - paper: pmid34055446 cited: true text: full license: by verdict: partial section: 3. Discussion quote: It has been hypothesized that an increase in IL-6 inflammatory markers seen in rheumatologic conditions can increase sympathetic drive, thus worsening POTS [4]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid33677650 cited: true text: full license: none verdict: partial section: 'POTS as a CNS disorder: proposed model' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid29102451 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome > Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p026. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - autoimmune_evidence papers: 17 evidence: - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Moreover, the immune response to COVID-19 can lead to autoimmunity, where the body produces antibodies that mistakenly target the autonomic nervous system [60]. note: 'Found by winnow, kev and lev in p020, p014, p019. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: POTS and other cardiovascular dysautonomias can develop after a SARS-CoV-2 infection. It is thought that these factors might be potent immune triggers that can evoke an autoimmune response in individuals who are susceptible. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid36947108 cited: true text: full license: none verdict: supports section: Commonalities with ME/CFS and other post-infection syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Discussion quote: Although post-COVID-19 autonomic pathophysiology is complex and has not been fully elucidated, autoimmunity is thought to be a critical aspect of POTS. Several reports have demonstrated that COVID-19 antibodies cross-react with autonomic nervous system components, such as ganglia, nerve fibers, and G-protein-coupled receptors, which can trigger dysfunction [3,11]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid35725868 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Autoimmunity > Autoimmunity in Long COVID quote: Autoimmunity has been implicated as one of the major mechanisms of Long COVID, leading to a higher risk, overall incidence, and range of autoimmune conditions after SARS-CoV-2 infection (Sharma and Bayry, 2023). note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Finally, COVID-19 may trigger development of autoantibodies, including antiphospholipid antibodies or antibodies against adrenergic and muscarinic receptors, that could then contribute to the cardiovascular manifestations of LHC (11, 13). note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: The underlying cause of dysautonomia post-COVID-19 infection is not well understood. However, a viral infection by SARS-CoV-2 triggering autoimmune response and direct neurotoxic effects has been suggested as an underlying cause for developing post-COVID-19 POTS [57,58]. note: 'Found by winnow, kev and lev in p027, p006. Claude judged: partial.' - paper: pmid37388279 cited: true text: full license: by verdict: partial section: 'Long Covid symptoms, effect on organs, and pathological mechanisms > Autonomic system sequelae > Mechanisms of autonomic dysfunction > Autoimmune attack:' quote: It is speculated that autoimmune mechanisms and autoantibody formation may be involved in the manifestation of autonomic symptoms in long Covid (121). It has also been shown that postural tachycardia syndrome and orthostatic hypotension are associated with these processes (122). note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37255928 cited: true text: full license: by verdict: partial section: Long Covid—the new pandemic quote: Notable autoantibodies include functionally active autoantibodies to the GPCRs (including α1- and β2-adrenoceptors, angiotensin receptor, nociception-like opioid receptor and muscarinic M2-receptor) [11]. This is significant for the overlap with POTS [12] and autonomic nervous system. note: 'Found by winnow, kev and lev in p009, p011. Claude judged: partial.' - paper: pmid36509178 cited: true text: full license: none verdict: partial section: Discussion > Hospitalization status quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36509178. Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid35852546 cited: true text: full license: none verdict: partial section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Plausibilität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What is the pathophysiology of POTS? quote: Postural orthostatic tachycardia syndrome may have an immunological cause. Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34992725 cited: true text: full license: by verdict: partial section: Arrhythmia in the COVID-19 Convalescent Period quote: Mechanistically, it is unclear why dysautonomia persists into the convalescent period of COVID-19 infection; however, similar to other viral syndromes, the cause is theorized to be a post-infectious autoimmune phenomenon. note: 'Found by winnow, kev and lev in p027. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Notably, antiphospholipid antibodies were detected in a patient with PASC-related POTS [60] who developed clinical signs and symptoms of antiphospholipid syndrome and mast cell activation syndrome following SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Diskussion quote: Im Zusammenhang mit den erhöhten adrenergen Autoantikörpern in unserem 1. Fallbeispiel erscheint es sinnvoll, die Induktion von Autoantikörpern nach SARS-COV-2-Infektion bei Kindern systematisch zu untersuchen. In einem aktuellen Review wird eindrucksvoll gezeigt, dass die SARS-CoV-2-Infektion als potenter Trigger der Bildung von Autoantikörpern angesehen wird [3]. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: partial.' - paper: pmid33262898 cited: true text: full license: by verdict: partial section: Discussion quote: Given the lag period of a few weeks between the COVID-19 infection and the onset of POTS symptoms, autoimmunity is a likely mechanism. However, our patient was not tested for autoantibodies cross-reacting with other receptors such as beta or muscarinic receptors. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - edge: - mast_cell_activation - proposed_mechanism_of - pots papers: 15 evidence: - paper: pmid41668453 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined. note: 'Found by winnow, kev and lev in p001, p031. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: supports section: 3. Discussion quote: POTS as an adverse event to HPV vaccine and the connection with EDS could be explained by mast cell activation causing POTS and EDS to present in patients post HPV-vaccination. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Mast Cell Activation Syndrome quote: Although an exact pathophysiologic mechanism has not been identified, activated mast cells may produce circulating vasodilators such as histamine, leading to flushing and orthostatic intolerance as part of a hyperadrenergic POTS presentation.[16] Vasodilation results in a compensatory sympathetic response with increased vascular resistance and tachycardia, ultimately leading to the release of norepinephrine and neuropeptide Y, which are thought to further activate mast cell degranulation and create a positive feedback loop. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid39165715 cited: true text: full license: by-nc verdict: supports section: Abstract > CONCLUSION quote: In the literature, MCA was considered to be one of the mechanisms leading to POTS. note: 'Found by winnow, kev and lev in p001, p004, p005. Claude judged: supports.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: 'Mast cell implication in hyperadrenergic POTS can be explained predominantly by histamine effects, which is a strong vasodilator, as follows: upon vasodilation, blood redistribution to interstitial and third spaces occurs, diminishing venous return and cardiac output, which is sensed by high-pressure receptors within the arterial wall of the carotid and aorta, causing increased baroreflex activation and enhancing sympathetic activity through the blood vessels in order to re-stablish hemodynamic stability [8].' note: 'Found by winnow, kev and lev in p006, p020. Claude judged: supports.' - paper: pmid35062788 cited: true text: full license: by verdict: supports section: 6. Discussion quote: Potential mechanisms underlying a causative MCAS–POTS linkage might involve inappropriate episodic primary release (again, either constitutive or reactive in nature) of MCs’ potently vasodilatory mediators, acting directly on the endothelium and vascular smooth muscle (e.g., histamine and kinins [68]), or primary MC release of other mediators, leading rapidly to vasodilation, e.g., neurostimulatory mediators causing neurally mediated vasodilation). note: 'Found by winnow, kev and lev in p007, p020, p021. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Finally, the role of excessive mast cell activation in the pathophysiology of POTS has been proposed. In mast cell activation disorder, the inappropriate release of histamine and other mast cell mediators in response to physical activity or orthostatic stress may lead to orthostatic tachycardia [49]. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid34398691 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: The cause of POTS in individual patients is usually unknown, despite a number of conditions having been implicated; these include viral illnesses, trauma, and various inflammatory diseases. Mast cell activation (MCA) disorder has also been implicated since chemical mediators released from mast cells may cause symptoms suggestive of POTS (eg, postural tachycardia, lightheadedness). note: 'Found by winnow, kev and lev in p006, p008, p038. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots > Mast Cell Activation quote: In an evaluation of young females with POTS, Shibao et al. (82) found that some of them had flushing episodes associated with OI, which suggests that MCA is likely involved in the hyperadrenergic mechanism for POTS (82). note: 'Found by winnow, kev and lev in p007, p018. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Discussion quote: A patient with severe POTS, MCAS and SIBO responded to a combination of LDN, IVIg and antibiotic therapy. We theorise that pre-existing MCAS was the driving force for hyperadrenergic POTS in this patient. note: 'Found by winnow, kev and lev in p014, p015. Claude judged: supports.' - paper: pmid15710782 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15710782. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: partial section: 1 Introduction quote: Mast cell activation disorder has been proposed to be associated with POTS with atypical symptom presentation, such as predominant gastrointestinal (GI) symptomatology (Kohno et al., 2021). note: 'Found by winnow, kev and lev in p002, p034. Claude judged: partial.' - paper: pmid36969375 cited: true text: full license: by-nc-nd verdict: partial section: Autonomic, allergic, and systemic abnormalities quote: Another theory in the literature is the relationship between POTS and mast cell activation disorder (MCAD). note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.5 Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p022. Claude judged: partial.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p070. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - postinfectious_evidence papers: 14 evidence: - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 1 Introduction quote: A direct link to the development of POTS as a sequela of COVID-19 infection in PASC gives great credence to the idea that the etiology of POTS involves an immunologic stressor such as a preceding viral illness. note: 'Found by winnow, kev and lev in p007, p001, p008. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Recently, POTS has been identified in ∼20% of cases of PASC, in which symptoms persist >4 weeks after the onset of COVID-19 illness.5,6 It is postulated that the cytokine storm from COVID-19 results in sympathetic dysregulation, causing an abnormal autonomic response in POTS.7 note: 'Found by winnow, kev and lev in p011, p023. Claude judged: supports.' - paper: pmid42245008 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42245008. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Evidence for LHC/POTS and immunologic dysregulation quote: Immunologic mechanisms discussed in the literature include persistent immune activation, T-cell/NK cell exhaustion, and development of autoantibodies (10–14). The study will investigate whether other immune mechanisms play a role in contributing to post-COVID-19 POTS. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: It has been observed that many patients with COVID-19 infection develop POTS as a delayed manifestation [9-11,19,22]. Some of these patients have never experienced any symptoms of POTS before. note: 'Found by winnow, kev and lev in p012, p017, p018. Claude judged: partial.' - paper: pmid36947108 cited: true text: full license: none verdict: partial section: Dysautonomia in PASC > What do we know about autonomic dysfunction in PASC? quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36947108. Found by winnow, kev and lev in p008, p024. Claude judged: partial.' - paper: pmid36614874 cited: true text: full license: by verdict: partial section: 4. Discussion quote: None of the PASC patients had similar symptoms of chronic fatigue, post-exercise malaise, or orthostatic intolerance prior to the COVID-19 infection. There are a few possibilities that can explain the post-infectious onset of the symptoms. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid35853576 cited: true text: full license: none verdict: partial section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p010, p012. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Inflammation and Autoimmunity quote: COVID-19 infection can cause a cytokine storm and inflammation that could trigger chronic neuronal dysregulation (47). One mechanism could be via the development of autoantibodies which cross-react with autonomic ganglia as part of acute and long-term COVID-19 infection, and lead to dysautonomia and POTS. note: 'Found by winnow, kev and lev in p008, p006, p009. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What is the pathophysiology of POTS? quote: Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 Recently, numerous cases of POTS33 and other forms of sinus tachycardia (e.g., inappropriate sinus tachycardia)34 after a SARS-CoV-2 infection have been reported. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34992725 cited: true text: full license: by verdict: partial section: Key Points quote: Inappropriate sinus tachycardia and postural orthostatic tachycardia syndrome seem to be common in the convalescent period of COVID-19 infection as a result of post-infectious dysautonomia. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Abstract quote: A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. note: 'Found by winnow, kev and lev in p001, p009. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Fall 2 quote: Basierend auf unseren Vorarbeiten über autonome Regulationsstörungen bei Kindern [2] und ersten Fallberichten aus der internistischen Kardiologie lag es nahe [6], dass diese postinfektiösen Probleme nach der SARS-CoV-2-Infektion Ausdruck eines sog. posturalen orthostatischen Tachykardiesyndroms (POTS) sind. note: 'Found by winnow, kev and lev in p011, p007, p010. Claude judged: partial.' - paper: pmid33262898 cited: true text: full license: by verdict: partial section: Conclusion quote: Autonomic dysfunction presenting as POTS can be a delayed manifestation of COVID-19 infection. note: 'Found by winnow, kev and lev in p011, p013. Claude judged: partial.' - edge: - post_vaccination_onset - proposed_mechanism_of - pots papers: 14 evidence: - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 1 Introduction quote: There are also many reports that vaccination against the SARS-CoV-2 virus may induce the development of POTS (23–25). note: 'Found by winnow, kev and lev in p006, p026. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Not only does contracting SARS-CoV-2 infection confer the possibility of developing long COVID and subsequent development of POTS, but recipients of the SARS-CoV-2 vaccine have also been shown to develop POTS at a higher rate. The proposed explanation is that an immunological response was elicited by the administration of the vaccination, resulting in similar symptoms to long COVID. note: 'Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid36475233 cited: true text: full license: by verdict: supports section: Discussion quote: However, POTS can be precipitated by immunologic stressors such as viral infection or vaccination [3]. Notably, reports of adult cases of new-onset POTS after COVID-19 mRNA vaccination have been emerging [12-15]. note: 'Found by winnow, kev and lev in p004, p001, p014. Claude judged: supports.' - paper: pmid35870086 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p014. Claude judged: supports.' - paper: pmid35062788 cited: true text: full license: by verdict: supports section: 6. Discussion quote: Taking all of the above knowledge into consideration, it thus becomes reasonable to hypothesize that the emergence of POTS soon after vaccination (whether against HPV or any other infectant) may be due to some constituent of the vaccine product (perhaps the immunogen, an adjuvant/excipient, or perhaps different factors in different patients) serving to “trigger” a cytokine storm (expressed by a variety of immune cells, including MCs, some of which may already be the dysfunctional MCs of MCAS), driving further (subclonal) evolution of (likely genomically unstable) MCAS, even in a patient previously not recognized to have MCAS. note: 'Found by winnow, kev and lev in p007, p021, p001. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Introduction quote: Onset of de novo POTS has been associated with viral infections, trauma, stress, surgery, and vaccinations. There have been studies, most notably in Denmark, that found de novo POTS after quadrivalent human papillomavirus (HPV) vaccine jabs [6,7]. note: 'Found by winnow, kev and lev in p001, p008, p003. Claude judged: supports.' - paper: pmid31001074 cited: true text: full license: by verdict: supports section: Introduction quote: This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al., 2015; Watari et al., 2018) support this hypothesis. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: partial section: Discussion quote: While post-vaccination cardiovascular autonomic dysfunction remains rare [32], small fiber neuropathy offers a plausible explanation for POTS cases manifesting after COVID-19 vaccination. note: 'Found by winnow, kev and lev in p045. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: However, there have been a few case reports published in peer-reviewed journals that show patients affected with POTS after receiving mRNA COVID-19 vaccination. The exact mechanism of action is not known at this time, but an autoimmune response to vaccination is one of the possible mechanisms. note: 'Found by winnow, kev and lev in p051. Claude judged: partial.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Discussion quote: POTS has been described following both mRNA-based Moderna COVID-19 and Pfizer-BioNTech COVID-19 vaccines [5-8]. Interestingly, the cases associated with the latter usually occur one to three weeks post-inoculation, a similar time frame to our patient. note: 'Found by winnow, kev and lev in p009, p010. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: We also found three case reports of POTS after COVID-19 vaccination. Although causality between POTS and vaccines cannot be inferred from these cases, some vaccines are associated with various autoimmune neurological diseases such as Guillain-Barre syndrome or multiple sclerosis [37]. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid36075372 cited: true text: full license: none verdict: partial section: Introduction > Other cardiovascular complications associated with COVID-19 vaccines > Arrhythmias quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36075372. Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 1. Introduction quote: There are also a number of reports of POTS developing subsequent to human papilloma virus immunization [22,23,24], implicating a potential role of inflammation and/or molecular mimicking as etiologies for the development of POTS. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid24102827 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24102827. Found by winnow, kev and lev in p002, p003, p004. Claude judged: partial.' - edge: - small_fiber_neuropathy_dx - proposed_mechanism_of - pots papers: 10 evidence: - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: Small fibre neuropathy in the lower limbs is the primary reason for decreased release of norepinephrine, especially in the lower limbs [13]. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Discussion quote: Small fiber neuropathy is regarded as one of the potential mechanisms underlying the pathophysiology of POTS [20], and in our cohort, QSART abnormalities indicating postganglionic small fiber dysfunction occurred with similar frequency in post-COVID and post-vaccination POTS. note: 'Found by winnow, kev and lev in p045, p047. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: Due to the nature of POTS being an autonomic imbalance due to a small-fiber neuropathy, the patient was offered a traditional osteopathic approach and craniosacral therapy, which is postulated to restore autonomic function and balance. note: 'Found by winnow, kev and lev in p001, p003, p005. Claude judged: supports.' - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Results > Representative cases > Postural tachycardia syndrome > Patient 15 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: Small fiber neuropathy, characterized by damage to the small nerve fibers that control autonomic functions, is often associated with conditions like diabetes and autoimmune diseases, and its emergence in post-COVID-19 patients suggests a potential neuropathic component to the pathophysiology of Long-COVID POTS. Small fiber neuropathy may contribute to the impaired regulation of blood pressure and heart rate that is commonly observed in these patients [11]. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 7. The Role of Fibrinaloid Microclots in POTS quote: Small fiber neuropathy (SFN) has been well described in long COVID (e.g., [63,65,68,172]) and is a recognized cause of dysautonomia in the condition. SFN in long COVID can be driven by autoantibodies (already known to be associated with POTS and OH) or, potentially, by ischemia of the small fibres due to microclots. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Introduction quote: Besides hypovolemia, anemia, neurodegenerative aspects and connective tissue disorders, autoimmunity seems to play an important role in the pathogenesis of PoTS in some patients [[3], [4], [5], [6], [7]]. Moreover, small fiber neuropathy (SFN, neuropathic PoTS) could be detected in around 50 % of patients with PoTS [[8], [9], [10]]. note: 'Found by winnow, kev and lev in p006, p007. Claude judged: partial.' - paper: pmid33764697 cited: true text: full license: by verdict: partial section: Introduction quote: The notion that a neuropathic process may underlie the presentation of some patients with a postural tachycardia has prompted clinical investigations and yielded associations with disorders that are recognized causes of an autonomic and/or small fiber neuropathy. note: 'Found by winnow, kev and lev in p007, p027. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Introduction quote: Several lines of evidence point to a restricted peripheral neuropathy, specifically, sympathetic denervation predominantly in the lower hemibody, as a cause of POTS in some individuals. note: 'Found by winnow, kev and lev in p006, p030. Claude judged: partial.' - paper: pmid16943900 cited: true text: full license: by verdict: partial section: Pathophysiology of POTS > Neuropathic POTS quote: Considering that POTS patients have high plasma NE levels, it would seem paradoxical that a neuropathy is proposed as an underlying process. Yet some of them have a form of dysautonomia, with preferential denervation of sympathetic nerves innvervating the lower limbs [22-24]. note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - prolonged_bed_rest - proposed_mechanism_of - pots papers: 8 evidence: - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: Studies have shown that bed rest or deconditioning can contribute independently to the development of POTS, regardless of the underlying mechanism [5]. Longer periods of physical inactivity can lead to cardiac muscular atrophy, reduction in stroke volume and overall hypovolemia [14]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Introduction quote: The underlying mechanisms remain unknown [18, 19], but viral and/or immune-mediated factors, as well as prolonged bed rest and physical deconditioning, may all play a substantial role in the development or exacerbation of cardiovascular autonomic disorders (CAD), such as postural orthostatic tachycardia syndrome (POTS), OH, and VVS [1, 11, 15, 16]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid34987818 cited: true text: full license: by-nc verdict: supports section: Discussion quote: There are various pathophysiological mechanisms for developing OI in POTS. One mechanism broadly described is cardiovascular deconditioning following prolonged bed rest, resulting in cardiac atrophy, and subsequent physical deconditioning. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p059. Claude judged: supports.' - paper: pmid40538940 cited: true text: full license: by verdict: partial section: Introduction quote: Many teenage patients with PoTS experienced deconditioning; however, deconditioning is not the sole cause of tachycardia in PoTS (20, 21), and prolonged bed rest can exacerbate orthostatic intolerance, including PoTS (22). note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid30001836 cited: true text: full license: none verdict: partial section: 1. INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid22889291 cited: true text: full license: by verdict: partial section: Discussion quote: Our patient presented several risk factors for POTS. First, prolonged bed rest following coarctation repair may have been an initiating event for his physical deconditioning. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid18704621 cited: true text: full license: none verdict: partial section: Is the rise in heart rate with POTS really “excessive?” quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 18704621. Found by winnow, kev and lev in p011. Claude judged: partial.' - edge: - post_vaccination_onset - proposed_mechanism_of - autoimmune_evidence papers: 7 evidence: - paper: pmid35870086 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p013. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Discussion quote: Numerous post-vaccination disorders, such as Guillain-Barre syndrome and transverse myelitis, have been reported to exhibit cross-reacting antibodies. These antibodies are proposed to mechanistically react beyond target ganglionic acetylcholine receptors, and thus could explain the POTS pathogenesis in the setting of post-vaccination [11]. note: 'Found by winnow, kev and lev in p001, p008, p011. Claude judged: supports.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: In the three cases of postvaccination POTS, the symptoms and signs were almost identical to those of PASC, indicating that COVID-19 vaccines share the same target autoantibody epitope with PASC presenting as immune-mediated POTS. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Discussion quote: Although the exact mechanism of vaccine-induced POTS is not clear, the autoimmune pathophysiology might be a key component [13-15]. note: 'Found by winnow, kev and lev in p001, p004, p014. Claude judged: partial.' - paper: pmid36075372 cited: true text: full license: none verdict: partial section: Introduction > Other cardiovascular complications associated with COVID-19 vaccines > Arrhythmias quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36075372. Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 1. Introduction quote: There are also a number of reports of POTS developing subsequent to human papilloma virus immunization [22,23,24], implicating a potential role of inflammation and/or molecular mimicking as etiologies for the development of POTS. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid31001074 cited: true text: full license: by verdict: partial section: Introduction quote: This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al., 2015; Watari et al., 2018) support this hypothesis. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - edge: - systemic_autoimmune_disease - proposed_mechanism_of - pots papers: 7 evidence: - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Introduction quote: Primary POTS occur independently, without association with other diseases, while secondary POTS is linked to underlying conditions such as diabetes mellitus, amyloidosis, sarcoidosis, autoimmune disorders like lupus or Sjogren’s syndrome, chemotherapy, or post-viral illnesses including COVID-19 [10]. note: 'Found by winnow, kev and lev in p084, p009. Claude judged: supports.' - paper: pmid34035985 cited: true text: full license: by verdict: supports section: Discussion quote: Metabolic, systemic, and autoimmune diseases may also manifest as POTS. Common culprits include diabetes mellitus, amyloidosis, heavy metal poisoning, Sjögren’s syndrome, hypermobility syndrome, and paraneoplastic syndrome. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: A review of autoimmunity in POTS by Ref. [5] found that “patients with POTS have a higher than expected frequency of defined autoimmune disorders such as multiple sclerosis, lupus, Sjögren syndrome or celiac disease”. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What is the pathophysiology of POTS? quote: Postural orthostatic tachycardia syndrome may have an immunological cause. Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Other diseases that have been associated with POTS that have significant inflammation include sarcoidosis, alcoholism, Lupus, Sjogren’s Syndrome, heavy metal intoxication, and following chemotherapy [8,26]. note: 'Found by winnow, kev and lev in p003, p030, p033. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: partial.' - edge: - prolonged_bed_rest - proposed_mechanism_of - deconditioning_evidence papers: 6 evidence: - paper: pmid42458878 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: In addition, prolonged bed rest and reduced physical activity related to orthostatic headache may lead to cardiovascular deconditioning, which can further aggravate orthostatic intolerance and tachycardic responses on standing. note: 'Found by winnow, kev and lev in p061. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Hypovolaemia quote: COVID-19 can be associated with fever and nocturnal sweating, leading to hypovolaemia, and prolonged bed rest, leading to deconditioning and cardiac atrophy. note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid34987818 cited: true text: full license: by-nc verdict: supports section: Discussion quote: One mechanism broadly described is cardiovascular deconditioning following prolonged bed rest, resulting in cardiac atrophy, and subsequent physical deconditioning. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p059. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: First, prolonged bed rest following coarctation repair may have been an initiating event for his physical deconditioning. note: 'Found by winnow, kev and lev in p016, p018. Claude judged: supports.' - paper: pmid34265539 cited: true text: full license: none verdict: partial section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p030. Claude judged: partial.' - edge: - hypovolemic_evidence - proposed_mechanism_of - hyperadrenergic_evidence papers: 6 evidence: - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Hypovolaemia quote: Firstly, it has been suggested that POTS occurs due to decreased blood volume and deconditioning of the heart, which subsequently increases cardiac sympathetic nervous system (SNS) output (24, 32, 33). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Hypovolemia may trigger hyperadrenergic POTS and lead to cerebral hypoperfusion and the impairment of central autonomic networks [56]. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.2 Hyperadrenergic State quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid25713509 cited: true text: full license: by verdict: supports section: Neurovisceral phenotypes > Joint hypermobility > Association with psychiatric disorder quote: In disorders that typically involve impaired collagen (present in blood vessels) such as joint hypermobility and postural tachycardia syndrome it is likely that reduced venous return during standing due to venous pooling or denervation causing low plasma volume may be responsible for a an increased sympathetic state–as the body attempts to compensate for these abnormalities—resulting in orthostatic intolerance and associated symptoms (Bohora, 2010; Benarroch, 2012; Mathias et al., 2012). note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > POTS Pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid40027266 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: The pathophysiology remains elusive; however, central hypovolemia has been identified as the mechanism leading to venous pooling, hypovolemia, deconditioning, and hyperadrenergic state.16,17 note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - postinfectious_evidence - proposed_mechanism_of - neuropathic_evidence papers: 6 evidence: - paper: pmid37822957 cited: true text: full license: by verdict: supports section: Discussion quote: "Several hypotheses about possible pathomechanisms of POTS or dysautonomia in general after COVID-19\ \ infection have been proposed: imbalance of the renin-angiotensin-aldosterone system,\n\n26\n\n,\n\n29\n\ \ brainstem involvement,\n\n43\n\n,\n\n45\n\n,\n\n46\n autoreactivity to antibodies against SARS-CoV-2,\n\n\ 25\n\n,\n\n43\n\n,\n\n47\n dyshomeostasis of immune response\n\n42\n\n,\n\n44\n and denervation of peripheral\ \ sympathetic nerve fibers." note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Discussion quote: We suspect a neuropathic cause of POTS in our patient that may be secondary to a viral cause, due to his history of infection with COVID-19. note: 'Found by winnow, kev and lev in p015, p001, p020. Claude judged: supports.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. note: 'Found by winnow, kev and lev in p008, p027. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Neurotropism quote: Thus, it has been proposed that SARS-Cov2 could infect and damage extracardiac postganglionic SNS, leading to dysautonomia in a similar way to neuropathic POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: The cholinergic POTS subgroup is therefore consistent with the hypothesis that neuropathic POTS is a restricted autonomic neuropathy [6]. Post-ganglionic cholinergic dysautonomia is frequently associated with a viral infection and is most likely immune-mediated [6,39-45]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - paper: pmid20035362 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - systemic_autoimmune_disease - proposed_mechanism_of - autoimmune_evidence papers: 5 evidence: - paper: pmid41446482 cited: true text: full license: by verdict: partial section: Introduction quote: Primary POTS occur independently, without association with other diseases, while secondary POTS is linked to underlying conditions such as diabetes mellitus, amyloidosis, sarcoidosis, autoimmune disorders like lupus or Sjogren’s syndrome, chemotherapy, or post-viral illnesses including COVID-19 [10]. note: 'Found by winnow, kev and lev in p084, p009. Claude judged: partial.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: Patients with one AD are often more prone to others. A review of autoimmunity in POTS by Ref. [5] found that “patients with POTS have a higher than expected frequency of defined autoimmune disorders such as multiple sclerosis, lupus, Sjögren syndrome or celiac disease”. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Other diseases that have been associated with POTS that have significant inflammation include sarcoidosis, alcoholism, Lupus, Sjogren’s Syndrome, heavy metal intoxication, and following chemotherapy [8,26]. In essence, if POTS is an autoimmune disorder as defined by the presence of autoantibodies, it could also be considered an inflammatory disorder. note: 'Found by winnow, kev and lev in p003, p030. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: partial.' - edge: - mast_cell_activation - proposed_mechanism_of - hyperadrenergic_evidence papers: 5 evidence: - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Mast Cell Activation Syndrome quote: Although an exact pathophysiologic mechanism has not been identified, activated mast cells may produce circulating vasodilators such as histamine, leading to flushing and orthostatic intolerance as part of a hyperadrenergic POTS presentation.[16] Vasodilation results in a compensatory sympathetic response with increased vascular resistance and tachycardia, ultimately leading to the release of norepinephrine and neuropeptide Y, which are thought to further activate mast cell degranulation and create a positive feedback loop. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: Hence, mast cell and sympathetic activity could create a closed-loop mechanism with positive feedback, as exemplified by the gradually progressing symptoms reported by patients. The more the mast cell is activated, the more sympathetic hyperactivity is produced, and vice versa (Fig. 3). note: 'Found by winnow, kev and lev in p006, p020, p021. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Associations with mast cell activation disorders quote: However, Shibao et al. [95] tested the hypothesis that plasma histamine can cause sympathetic overactivity via vasodilatation and compared POTS patients presenting flushing and raised urinary methylhistamine (a mast cell mediator metabolite) with patients reporting flushing but with normal urinary metabolites. These MCA/POTS patients had predominant flushing breathlessness, headache, lightheadedness, excessive diuresis, diarrhoea, nausea and vomiting, and had a marked hyperadrenergic orthostatic response, with higher noradrenaline levels and exaggerated blood pressure rise on standing compared with the POTS and control groups [95]. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Discussion quote: We theorise that pre-existing MCAS was the driving force for hyperadrenergic POTS in this patient. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p070. Claude judged: partial.' - edge: - postinfectious_evidence - proposed_mechanism_of - hyperadrenergic_evidence papers: 5 evidence: - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Conclusions quote: Although our understanding is not entirely clear, some postulated mechanisms consist of autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-COV-2, or sympathetic nervous system stimulation secondary to infection. note: 'Found by winnow, kev and lev in p012, p079. Claude judged: supports.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Hyperadrenergic states from infection, hypovolemia, and deconditioning are implicated in development of orthostatic intolerance post-pandemic. note: 'Found by winnow, kev and lev in p010, p029. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p017, p030. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Discussion quote: Additionally, the role of angiotensin-converting enzyme 2 (ACE2) receptor dysfunction has been implicated in the etiology of POTS, as COVID-19 attenuates ACE2 receptor activity and consequently upregulates sympathetic activation [14]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Discussion quote: It is postulated that the cytokine storm from the COVID-19 infection results in sympathetic dysregulation, causing the abnormal autonomic response in POTS [6]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - edge: - autoimmune_evidence - proposed_mechanism_of - neuropathic_evidence papers: 5 evidence: - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Discussion quote: Some cases of neuropathic POTS are thought to arise from immune-mediated neuropathy. note: 'Found by winnow, kev and lev in p037, p038, p039. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: 'POTS as a CNS disorder: proposed model' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: supports section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p034. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: Post-ganglionic cholinergic dysautonomia is frequently associated with a viral infection and is most likely immune-mediated [6,39-45]. The absence of a distal to proximal gradient in sudomotor deficits, observed by us and by others lends additional support to the possibility that an immune-mediated process underlies neuropathic POTS [5,8,37]. note: 'Found by winnow, kev and lev in p040. Claude judged: partial.' - edge: - anxiety_depression - proposed_mechanism_of - hyperadrenergic_evidence papers: 4 evidence: - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: What’s more, researchres confirmed that anxiety and depression could act on hypothalamic-pituitary-adrenocortical axis (HPA) and produce hyperactivity of the sympathetic nervous system (Remme, 1998). Studies have shown that depression and anxiety could increase sympathetic excitability, upregulated levels of catecholamine in the blood, and heart rate (Wang et al., 2018). note: 'Found by winnow, kev and lev in p007, p020. Claude judged: supports.' - paper: pmid39540412 cited: true text: full license: by-nc verdict: partial section: How to Explain the Pathophysiology to Patients and Families quote: Anxiety about these symptoms potentiates the pathophysiology, as additional excessive adrenaline is made in response—drying out the patient, increasing fluid requirements, and cycling the pathophysiology. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid35802513 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35802513. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Introduction quote: Anxiety with its hyperadrenergic response can mimic POTS. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - hyperadrenergic_evidence papers: 4 evidence: - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p017, p030. Claude judged: supports.' - paper: pmid41859298 cited: true text: full license: by-nc verdict: partial section: Neuroinflammation quote: Importantly, systemic abnormalities consisting of central hypovolemia, hyperadrenergic response and downstream autonomic neuropathy resulting from central autonomic network dysregulation may correlate to the hypovolemic, hyperadrenergic and neuropathic POTS phenotypes and may localize to the dorsolateral medulla and hypothalamus via nucleus tractus solitarius, dorsal motor nucleus of the vagus and dorsal longitudinal fasciculus traversing near the floor of the fourth ventricle.22,52 note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: partial section: DISCUSSION quote: They found gliosis and astrogliosis in a patchy pattern near the nuclei that control sympathetic activity in patients deceased by COVID-19 [17]. Malfunction of these nuclei could give rise to sympathetic hyperactivity, producing HR and SBP disturbances during postural changes, as could be seen in hyperadrenergic POTS [7]. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p040. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - neuropathic_evidence papers: 4 evidence: - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Discussion quote: We suspect a neuropathic cause of POTS in our patient that may be secondary to a viral cause, due to his history of infection with COVID-19. note: 'Found by winnow, kev and lev in p015, p001. Claude judged: supports.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. note: 'Found by winnow, kev and lev in p008, p027. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Neurotropism quote: Thus, it has been proposed that SARS-Cov2 could infect and damage extracardiac postganglionic SNS, leading to dysautonomia in a similar way to neuropathic POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: Small fiber neuropathy, characterized by damage to the small nerve fibers that control autonomic functions, is often associated with conditions like diabetes and autoimmune diseases, and its emergence in post-COVID-19 patients suggests a potential neuropathic component to the pathophysiology of Long-COVID POTS. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - edge: - hypermobility_heds - proposed_mechanism_of - pots papers: 4 evidence: - paper: pmid39582682 cited: true text: full license: by verdict: supports section: Headache disorders in hEDS and HSD > Orthostatic headaches > Postural tachycardia syndrome quote: The exact mechanism behind increased prevalence of PoTS in hypermobile patients remains elusive. One of the more accepted hypotheses relates to excessive distensibility of the veins, due to the underlying HCTD, leading to venous pooling and reduced venous return. note: 'Found by winnow, kev and lev in p022, p024. Claude judged: supports.' - paper: pmid35620060 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Furthermore, EDS may predispose patients to abnormal venous distention during orthostatic stress, leading to the venous pooling found in POTS. note: 'Found by winnow, kev and lev in p017, p004, p018. Claude judged: supports.' - paper: pmid19946638 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Patients with joint hypermobility syndrome even have more difficulty owing to loss of supporting connective tissues in the vessels. Orthostatic intolerance develops in these patients due to the presence of abnormally elastic connective tissue in the vasculature. note: 'Found by winnow, kev and lev in p006, p007. Claude judged: supports.' - paper: pmid34055418 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The association between POTS and JHS can be explained by predominant peripheral neuropathy in the autonomous system and a failure of the peripheral vascular system to maintain resistance in areas exposed to stress due to orthostasis, blood stasis in the lower limbs, or pathologies of the central nervous system [11]. note: 'Found by winnow, kev and lev in p005, p012. Claude judged: partial.' - edge: - hypovolemic_evidence - proposed_mechanism_of - cerebral_hypoperfusion_evidence papers: 3 evidence: - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 4 Discussion > 4.2 Hypovolemia-induced POTS quote: In cases of hypovolemia, transitioning from a supine to an upright position leads to insufficient blood supply, reducing the blood flow to the brain. note: 'Found by winnow, kev and lev in p001, p047, p050. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Hypovolemia may trigger hyperadrenergic POTS and lead to cerebral hypoperfusion and the impairment of central autonomic networks [56]. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: 'POTS as a CNS disorder: proposed model' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026. Claude judged: supports.' - edge: - small_fiber_neuropathy_dx - proposed_mechanism_of - neuropathic_evidence papers: 3 evidence: - paper: pmid41675297 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: This is hypothesized to be due to small fiber neuropathy leading to decreased adrenergic vasoconstriction in the legs or the splanchnic vasculature, causing baroreflex unloading, decreased reflex cardiovagal stimulation, increased reflex sympathetic excitation, and reflex tachycardia.46 note: 'Found by winnow, kev and lev in p048. Claude judged: supports.' - paper: pmid33764697 cited: true text: full license: by verdict: partial section: Introduction quote: The notion that a neuropathic process may underlie the presentation of some patients with a postural tachycardia has prompted clinical investigations and yielded associations with disorders that are recognized causes of an autonomic and/or small fiber neuropathy. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid16943900 cited: true text: full license: by verdict: partial section: Pathophysiology of POTS > Neuropathic POTS quote: Considering that POTS patients have high plasma NE levels, it would seem paradoxical that a neuropathy is proposed as an underlying process. Yet some of them have a form of dysautonomia, with preferential denervation of sympathetic nerves innvervating the lower limbs [22-24]. note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - anxiety_depression - proposed_mechanism_of - pots papers: 3 evidence: - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: Anxiety and depression emotion might be involved in the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p004, p007, p020. Claude judged: supports.' - paper: pmid40763323 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Furthermore, the higher prevalence of palpitations observed during the pandemic may be associated with elevated anxiety levels and psychological stress.14-17 note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid39540412 cited: true text: full license: by-nc verdict: partial section: How to Explain the Pathophysiology to Patients and Families quote: Anxiety about these symptoms potentiates the pathophysiology, as additional excessive adrenaline is made in response—drying out the patient, increasing fluid requirements, and cycling the pathophysiology. Explaining this to patients in this way takes the focus from anxiety as a primary cause, but still informs them that it is a contributor to symptoms and must be addressed just like the other parts of treatment. note: 'Found by winnow, kev and lev in p009, p019. Claude judged: partial.' - edge: - iron_deficiency - proposed_mechanism_of - pots papers: 3 evidence: - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots quote: Current perspectives on the pathogenesis of POTS have been categorized as altered central blood volume, abnormal autonomic reflexes and elevated sympathetic tone, damaged skeletal muscle pump activity, local vascular tension regulation dysfunction, iron insufficiency, mast cell activation (MCA), and autoimmune dysfunction (3, 6, 12). note: 'Found by winnow, kev and lev in p017, p007. Claude judged: supports.' - paper: pmid23720007 cited: true text: abstract license: none verdict: supports section: Abstract > Interpretation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23720007. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Additional Associations and Postural Orthostatic Tachycardia Syndrome Mimickers > Iron Deficiency and Anemia quote: Whether iron deficiency is specifically related to POTS or serves as a mimicker via diminished venous return is still under review.[11] Dodson et al. found an association between restless legs syndrome, a condition often caused by iron deficiency anemia, and POTS.[52] note: 'Found by winnow, kev and lev in p038. Claude judged: partial.' - edge: - sleep_disturbance - proposed_mechanism_of - pots papers: 3 evidence: - paper: pmid25474569 cited: true text: full license: by verdict: supports section: Discussion quote: Irwin et al. found that patients with insomnia had increased nocturnal catecholamine levels as compared with controls [34] which might contribute the pathophysiology of POTS. note: 'Found by winnow, kev and lev in p028, p006. Claude judged: supports.' - paper: pmid42254140 cited: true text: full license: by verdict: partial section: Body quote: Dysregulation in any of these inputs can result in fragmented sleep, which can increase sympathetic nervous system activity, compounding POTS symptoms like tachycardia, fatigue, and exercise intolerance[4,9]. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid35303039 cited: true text: full license: by verdict: partial section: Discussion quote: In addition, sleeping disorder was common in pediatric postural tachycardia syndrome (POTS) that was thought to have similar hemodynamic characteristics to pediatric STS [1, 21]. Sleeping duration of less than 8 hours was deemed to be a risk factor for pediatric POTS [7]. note: 'Found by winnow, kev and lev in p006, p024. Claude judged: partial.' - edge: - hyperadrenergic_evidence - proposed_mechanism_of - cerebral_hypoperfusion_evidence papers: 2 evidence: - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Discussion > Pulmonary determinants quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p033, p039. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS (Table 1) > Hyperadrenergic POTS quote: Another manifestation of increased SNA during orthostasis in POTS patients includes possibly increasing coherence and blunting cerebral autoregulation leading to decreased cerebral blood flow (Ocon et al., 2009). note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - edge: - neuropathic_evidence - proposed_mechanism_of - hyperadrenergic_evidence papers: 2 evidence: - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p004, p031. Claude judged: partial.' - paper: pmid12577219 cited: true text: abstract license: none verdict: partial section: Abstract > Method quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 12577219. Found by winnow, kev and lev in p002. Claude judged: partial.' - edge: - autoimmune_evidence - proposed_mechanism_of - hypovolemic_evidence papers: 2 evidence: - paper: pmid33677650 cited: true text: full license: none verdict: supports section: 'POTS as a CNS disorder: proposed model' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid37393658 cited: true text: full license: none verdict: partial section: DISCUSSION > RAAS Abnormalities in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p026. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - hypovolemic_evidence papers: 2 evidence: - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Simultaneously, long COVID-19 can cause hypovolemia through various pathways, including decreased intake due to illness or direct viral effects on gastrointestinal systems leading to losses through diarrhea [64]. The resultant decrease in blood volume challenges the body’s ability to maintain adequate blood circulation, especially upon standing, which can trigger or exacerbate POTS symptoms. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 7. The Role of Fibrinaloid Microclots in POTS quote: Other mechanisms for POTS in long COVID may include:Relative hypovolemia secondary to inadequate peripheral vasoconstriction. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - edge: - neuropathic_evidence - proposed_mechanism_of - postinfectious_evidence papers: 2 evidence: - paper: pmid37822957 cited: true text: full license: by verdict: partial section: Discussion quote: "Several hypotheses about possible pathomechanisms of POTS or dysautonomia in general after COVID-19\ \ infection have been proposed: imbalance of the renin-angiotensin-aldosterone system,\n\n26\n\n,\n\n29\n\ \ brainstem involvement,\n\n43\n\n,\n\n45\n\n,\n\n46\n autoreactivity to antibodies against SARS-CoV-2,\n\n\ 25\n\n,\n\n43\n\n,\n\n47\n dyshomeostasis of immune response\n\n42\n\n,\n\n44\n and denervation of peripheral\ \ sympathetic nerve fibers." note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: Mechanisms of Dysautonomia Leading to Postural Orthostatic Tachycardia Syndrome > Neurotropism quote: Thus, it has been proposed that SARS-Cov2 could infect and damage extracardiac postganglionic SNS, leading to dysautonomia in a similar way to neuropathic POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - edge: - gi_dysmotility - proposed_mechanism_of - pots papers: 2 evidence: - paper: pmid29549458 cited: true text: full license: none verdict: partial section: Results > Proposed Pathophysiology for Gastrointestinal Symptoms in Postural Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p024, p014. Claude judged: partial.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: partial section: Introduction > Concurrent clinical syndromes > Irritable bowel syndrome (IBS) quote: Although rarely performed, plethysmography may demonstrate splanchnic venous pooling in patients with IBS.8 The baroreflex response to reduced venous return (consequent to histamine or localized small molecule related vasodilation) can result in POTS. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - cerebral_hypoperfusion_evidence papers: 1 evidence: - paper: pmid39857750 cited: true text: full license: by verdict: partial section: '3. Dorsolateral Medulla: Localization for POTS and Long COVID' quote: Cerebral hypoperfusion is one of the major mechanisms of POTS, autonomic dysfunction, myalgic encephalomyelitis/chronic fatigue syndrome and probably Long COVID [6]. note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - edge: - hypovolemic_evidence - proposed_mechanism_of - deconditioning_evidence papers: 1 evidence: - paper: pmid25168872 cited: true text: full license: by verdict: partial section: Discussion quote: Volume depletion is a cardinal feature of the deconditioned state (Coyle et al. 1986) and POTS (Benarroch 2012; Raj 2013) and may account for much of the observed reduction in heart size in patients with CFS (Miwa and Fujita 2008; Hurwitz et al. 2010). note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - edge: - long_covid - proposed_mechanism_of - deconditioning_evidence papers: 1 evidence: - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p040. Claude judged: partial.' - edge: - postinfectious_evidence - proposed_mechanism_of - deconditioning_evidence papers: 1 evidence: - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Post–COVID-19 POTS > C.2. Possible mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p017. Claude judged: supports.' - edge: - surgery_onset - proposed_mechanism_of - deconditioning_evidence papers: 1 evidence: - paper: pmid22889291 cited: true text: full license: by verdict: partial section: Discussion quote: First, prolonged bed rest following coarctation repair may have been an initiating event for his physical deconditioning. note: 'Found by winnow, kev and lev in p016, p018. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - proposed_mechanism_of - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p026. Claude judged: supports.' - edge: - hypermobility_heds - proposed_mechanism_of - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid25713509 cited: true text: full license: by verdict: supports section: Neurovisceral phenotypes > Joint hypermobility > Association with psychiatric disorder quote: In disorders that typically involve impaired collagen (present in blood vessels) such as joint hypermobility and postural tachycardia syndrome it is likely that reduced venous return during standing due to venous pooling or denervation causing low plasma volume may be responsible for a an increased sympathetic state–as the body attempts to compensate for these abnormalities—resulting in orthostatic intolerance and associated symptoms (Bohora, 2010; Benarroch, 2012; Mathias et al., 2012). note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - edge: - sleep_disturbance - proposed_mechanism_of - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid35303039 cited: true text: full license: by verdict: supports section: Discussion quote: Therefore, it can be speculated that the reduced sleeping duration increased sympathetic excitement, causing endocrine hormone secretion disorders. In other words, children with insomnia may lead to a maladaptive daytime sympathetic excitement, which might be the cause of STS [24]. note: 'Found by winnow, kev and lev in p006, p024. Claude judged: supports.' - edge: - hyperadrenergic_evidence - proposed_mechanism_of - hypovolemic_evidence papers: 1 evidence: - paper: pmid34268642 cited: true text: full license: none verdict: partial section: Autonomic Disorders and Headache quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34268642. Found by winnow, kev and lev in p015. Claude judged: partial.' - edge: - mast_cell_activation - proposed_mechanism_of - hypovolemic_evidence papers: 1 evidence: - paper: pmid37241210 cited: true text: full license: by verdict: partial section: 3. Association with Postural Tachycardia Syndrome, Reduced Cerebral Blood Flow and Orthostatic Intolerance quote: 'Histamine is probably the most important mediator released by overactivated mast cells. Upon a histamine discharge, the excess of histamine has the potential to worsen the orthostatic intolerance (OI) via several vascular mechanisms: (1) intestinal hyperemia and steal effect when dealing with intestinal releases, (2) a systemic vasodilating effect will disturb the highly coordinated orthostatic regulation, not only affecting arterial but even stronger venous vessels.' note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - edge: - prolonged_bed_rest - proposed_mechanism_of - hypovolemic_evidence papers: 1 evidence: - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Cardiovascular pathophysiology quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p017. Claude judged: partial.' - edge: - post_vaccination_onset - proposed_mechanism_of - neuropathic_evidence papers: 1 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: partial section: Discussion quote: A recent study found, however, that vaccination against COVID-19 can predispose individuals to develop small fiber neuropathy [56]. Small fiber neuropathy is regarded as one of the potential mechanisms underlying the pathophysiology of POTS [20], and in our cohort, QSART abnormalities indicating postganglionic small fiber dysfunction occurred with similar frequency in post-COVID and post-vaccination POTS. note: 'Found by winnow, kev and lev in p045. Claude judged: partial.' - edge: - systemic_autoimmune_disease - proposed_mechanism_of - neuropathic_evidence papers: 1 evidence: - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - edge: - hyperadrenergic_evidence - proposed_mechanism_of - postinfectious_evidence papers: 1 evidence: - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Conclusions quote: Although our understanding is not entirely clear, some postulated mechanisms consist of autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-COV-2, or sympathetic nervous system stimulation secondary to infection. note: 'Found by winnow, kev and lev in p001, p012, p079. Claude judged: partial.' - edge: - mast_cell_activation - proposed_mechanism_of - postinfectious_evidence papers: 1 evidence: - paper: pmid36981522 cited: true text: full license: by verdict: supports section: 5. Discussion quote: Afrin and colleagues have hypothesized that pre-existing MCAS might predispose patients to develop long-COVID after a SARS-CoV-2 infection by contributing to a hyperinflammatory response [35]. note: 'Found by winnow, kev and lev in p034. Claude judged: supports.' - edge: - hormonal_transition_onset - proposed_mechanism_of - pots papers: 1 evidence: - paper: pmid31798399 cited: true text: full license: by verdict: partial section: Abstract quote: Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. note: 'Found by winnow, kev and lev in p005, p054, p001. Claude judged: partial.' - edge: - me_cfs - proposed_mechanism_of - pots papers: 1 evidence: - paper: pmid37241210 cited: true text: full license: by verdict: partial section: 3. Association with Postural Tachycardia Syndrome, Reduced Cerebral Blood Flow and Orthostatic Intolerance quote: The association of MCA with POTS, as an example for orthostatic stress, may be via ME/CFS or separate. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - edge: - surgery_onset - proposed_mechanism_of - pots papers: 1 evidence: - paper: pmid22889291 cited: true text: full license: by verdict: partial section: Discussion quote: Our patient presented several risk factors for POTS. First, prolonged bed rest following coarctation repair may have been an initiating event for his physical deconditioning. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - pots papers: 124 evidence: - paper: pmid42458878 cited: true text: full license: by-nc-nd verdict: supports section: METHODS > Outcome assessment quote: 'Orthostatic hemodynamic abnormality was defined as the presence of any of the following during the HUT test: classical orthostatic hypotension (OH), delayed OH, POTS, or syncope, based on the 2018 European Society of Cardiology guidelines.' note: 'Found by winnow, kev and lev in p041, p059. Claude judged: supports.' - paper: pmid42342403 cited: true text: full license: by verdict: supports section: Methods > Eligibility criteria > Screening of participants without a prior diagnosis quote: A ΔHR of ≥30 bpm within 10 min of head-up tilt (70°), in the absence of orthostatic hypotension (SBP fall ≥20 mm Hg or diastolic BP fall ≥10 mm Hg), fulfils the diagnostic criteria for POTS; in participants with a ΔHR of 25–29 bpm, the diagnostic criteria are likewise considered fulfilled if typical orthostatic symptoms are present and clinical judgement supports the diagnosis. note: 'Found by winnow, kev and lev in p028, p030, p023. Claude judged: supports.' - paper: pmid42273028 cited: true text: full license: by verdict: supports section: Materials and methods > Participants quote: 'We retrospectively identified 382 patients diagnosed with POTS via the head-up tilt table test (HUTT), a diagnostic tool with demonstrated higher sensitivity for POTS diagnosis than basic orthostatic vital signs at the Cleveland Clinic between 2018 and 2020 (13). A diagnosis of POTS was confirmed by HUTT when the following criteria, identified by Stallkamp-Tidd et al. (2), were met:' note: 'Found by winnow, kev and lev in p011, p002, p012. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Materials and methods quote: All patients meeting the standardised definition of POTS, whose diagnosis was confirmed with positive tilt table testing between August 2023 and August 2024. A tilt table test was considered positive if the heart rate increased by >=30 bpm or the heart rate was >= 120 bpm within 10 minutes of standing up from a recumbent position, notably in the absence of any orthostatic hypotension (>20 mmHg drop in SBP). note: 'Found by winnow, kev and lev in p002, p016, p026. Claude judged: supports.' - paper: pmid41420770 cited: true text: full license: none verdict: supports section: 'Materials and Methods: > Autonomic testing procedures:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41420770. Found by winnow, kev and lev in p010, p026, p034. Claude judged: supports.' - paper: pmid41300849 cited: true text: full license: by verdict: supports section: 2. Materials and Methods > 2.1. Study Protocol quote: After head-up tilt testing (HUTT), 22 patients (7.7% of 287) with post-COVID-19 CFS, 27 patients (5.4% of 501) with CFS of insidious onset, and 20 patients (7.5% of 267) with syncope fulfilled diagnostic criteria for POTS. note: 'Found by winnow, kev and lev in p007, p031, p041. Claude judged: supports.' - paper: pmid41156242 cited: true text: full license: by verdict: supports section: Abstract quote: Tilt-table testing was abnormal in 82.0% of cases, revealing orthostatic hypotension, reflex syncope, or postural tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p014, p019, p001. Claude judged: supports.' - paper: pmid40959677 cited: true text: full license: by-nc verdict: supports section: Abstract > Background quote: The head-up test (HUT) or head-up tilt test (HUTT) is typically required to confirm the diagnosis of POTS. note: 'Found by winnow, kev and lev in p001, p009, p039. Claude judged: supports.' - paper: pmid40761644 cited: true text: full license: by verdict: supports section: Patients and methods > Examination of orthostatic intolerance quote: POTS was defined as a sustained increase in heart rate of ≥30 beats per minute, accompanied by characteristic orthostatic symptoms in the absence of postural hypotension. This abbreviated procedure is consistent with the diagnostic criteria outlined by Freeman et al. (22), and was selected to allow standardized yet clinically feasible assessment in a non-cardiology outpatient setting. note: 'Found by winnow, kev and lev in p015, p010, p018. Claude judged: supports.' - paper: pmid40585261 cited: true text: full license: by verdict: supports section: 'Materials and Methods > Autonomic testing procedures:' quote: Standard diagnostic criteria were used to identify POTS, orthostatic hypotension, and orthostatic hypertension during tilt table testing. note: 'Found by winnow, kev and lev in p012, p028. Claude judged: supports.' - paper: pmid40533427 cited: true text: full license: by verdict: supports section: Body quote: The confirmed diagnosis was based on international criteria, including a sustained heart rate increase of at least 30 beats per minute or at least 40 beats per minute in adolescents (16–19 years of age) during a 10‐minute active standing test or head‐up tilt table test, the absence of orthostatic hypotension, and unexplained symptoms of orthostatic intolerance lasting at least three months. note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid40437589 cited: true text: full license: by verdict: supports section: Materials and methods > Definition of positive responses to HUTT quote: Positive responses to HUTT included vasovagal syncope (VVS), postural orthostatic tachycardia syndrome (POTS), and orthostatic hypertension (OHT). note: 'Found by winnow, kev and lev in p003, p011, p016. Claude judged: supports.' - paper: pmid40433210 cited: true text: full license: by-nc-nd verdict: supports section: Methods > HUTTs quote: A HUTT was considered positive for POTS if a sustained increase in heart rate, of > 30 beats per minute within 10 minutes of tilting, was noted in the absence of a drop in blood pressure of > 20/10 mm Hg. note: 'Found by winnow, kev and lev in p005, p015, p018. Claude judged: supports.' - paper: pmid40432440 cited: true text: full license: by verdict: supports section: Methods quote: Inclusion criteria were symptoms of orthostatic intolerance with a diagnosis of POTS or vasovagal syncope confirmed by head-up tilt test. note: 'Found by winnow, kev and lev in p012, p016. Claude judged: supports.' - paper: pmid40271232 cited: true text: full license: by verdict: supports section: Materials and methods quote: The tilt table test is the current standard for POTS diagnosis, which involves measuring a patient’s heart rate and blood pressure when they are supine compared to when they are tilted upward at a 70° angle from the horizontal plane. note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid40003288 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Currently, the only validated tool for diagnosis of POTS in adolescents is the head up tilt table testing [13]. During head-up tilt table testing, patients are secured to a table with a footplate in a supine position for at least 10 min, and then the table is elevated to approximately 70 degrees (at least 60 degrees) for a minimum of 10 additional minutes. note: 'Found by winnow, kev and lev in p006, p002. Claude judged: supports.' - paper: pmid39552985 cited: true text: full license: by verdict: supports section: Abstract quote: The diagnosis of POTS was established only four years later by a tilt table test. note: 'Found by winnow, kev and lev in p009, p001, p033. Claude judged: supports.' - paper: pmid39308845 cited: true text: full license: by verdict: supports section: Materials and methods quote: Patients were diagnosed with POTS based on autonomic testing, applying the criteria of a 40 bpm increase in heart rate during a head-up tilt table test without concurrent hypotension, as per the published diagnostic guidelines for pediatric populations [1]. note: 'Found by winnow, kev and lev in p005, p017. Claude judged: supports.' - paper: pmid39165715 cited: true text: full license: by-nc verdict: supports section: Abstract > METHODS quote: Serum tryptase levels were obtained from all patients before the TILT-table test, and serum tryptase levels were re-studied after the test was terminated in patients with positive TILT-table tests for POTS. Patients diagnosed with POTS were classified as Group 1, and other patients were classified as Group 2. note: 'Found by winnow, kev and lev in p002, p019. Claude judged: supports.' - paper: pmid39109119 cited: true text: full license: by verdict: supports section: Case presentation quote: The 72-hour Holter did demonstrate persistent sinus tachycardia and head-up tilt-table testing confirmed POTS (Table 1, Figure 1, Figure 2). Following a passive head-up tilt-table testing, the patient’s heart rate increased by >30 bpm to a maximum of 144 bpm, clinching the diagnostic criteria for POTS. note: 'Found by winnow, kev and lev in p006, p012. Claude judged: supports.' - paper: pmid38962840 cited: true text: full license: by-nc-nd verdict: supports section: METHODS quote: The HUT was utilized in this context as a well‐established standardized method to reaffirm the diagnosis of POTS on the study day [1, 2]. note: 'Found by winnow, kev and lev in p013, p014. Claude judged: supports.' - paper: pmid38585346 cited: true text: full license: by verdict: supports section: Methods > Reviewed testing quote: Tilt table is diagnostic for POTS if within this 10-min time, the patient has a sustained heart rate increase of at least 30 beats per minute in the absence of orthostatic hypotension or another condition that may explain the sinus tachycardia. note: 'Found by winnow, kev and lev in p010, p002. Claude judged: supports.' - paper: pmid38486257 cited: true text: full license: by verdict: supports section: Methods > Study participants quote: 'All children fulfilled the following diagnostic criteria for VVS or POTS: (1) mainly older children; (2) presence of OI symptoms; (3) positive HUTT; and (4) absence of other conditions that might cause similar symptoms, such as cerebrovascular disorders and organic heart diseases [2].' note: 'Found by winnow, kev and lev in p008, p009. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: 2 Materials and methods > 2.2 Study population > 2.2.1 The POTS cohort > 2.2.1.2 Cardiovascular autonomic testing quote: POTS diagnosis was defined as symptoms of orthostatic intolerance lasting for ≥3 months associated with a pathological tilt test showing a HR increase >30 bpm from supine position or a HR > 120 bpm in standing, with no evidence of orthostatic hypotension (Brignole et al., 2018). note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Methods quote: Patients underwent a standardized testing protocol to confirm the diagnosis of POTS (head up tilt) and specific laboratory testing to establish the POTS phenotype(s) to guide therapy. note: 'Found by winnow, kev and lev in p003, p007. Claude judged: supports.' - paper: pmid38033543 cited: true text: full license: by verdict: supports section: Materials and methods > Standing test and HUTT > HUTT quote: Although the standing test is relatively simple and should be prioritized in clinical practice, the HUTT can also be used to help diagnose of POTS. note: 'Found by winnow, kev and lev in p011, p014. Claude judged: supports.' - paper: pmid37508741 cited: true text: full license: by verdict: supports section: 2. Materials and Methods > 2.3. HUTT quote: 'HUTT is divided into two steps: basic head-up tilt test (BHUT) and sublingual nitroglycerin head-up tilt test (SNHUT). In this study, only BHUT was used to diagnose POTS.' note: 'Found by winnow, kev and lev in p006, p007. Claude judged: supports.' - paper: pmid37443510 cited: true text: full license: by verdict: supports section: 1. Introduction quote: A standing test or head-up tilt test (HUTT) can provide important evidence for the diagnosis of POTS. note: 'Found by winnow, kev and lev in p002, p005, p008. Claude judged: supports.' - paper: pmid37378800 cited: true text: full license: by verdict: supports section: Materials and methods > Autonomic testing quote: Postural orthostatic tachycardia syndrome (POTS) was defined as a persistent increase in heart rate of at least 30 beats per minute within 10 min of upright tilt, in the absence of either classical or delayed orthostatic hypotension. note: 'Found by winnow, kev and lev in p016, p026. Claude judged: supports.' - paper: pmid36518687 cited: true text: full license: by verdict: supports section: Materials and methods > Diagnostic procedures > Head-up tilt test quote: VVS diagnosis and its hemodynamic subtypes, POTS, OH, and OHT, were identified using HUTT (7). note: 'Found by winnow, kev and lev in p010, p013. Claude judged: supports.' - paper: pmid36397456 cited: true text: full license: by-nc verdict: supports section: 3. Results quote: 'Based on HUTT results, 70 patients (13.0%) were diagnosed with POTS: 33 adolescents (22.4%), 37 adults (13.8%), and no older individuals.' note: 'Found by winnow, kev and lev in p005, p014, p016. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: HUT is considered as a golden standard for POTS diagnosis61. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid36111700 cited: true text: full license: by-nc verdict: supports section: Methods > Investigation protocol quote: POTS diagnosis was defined by symptoms of orthostatic intolerance lasting for ≥6 months associated with pathological head‐up tilt test or active standing test showing HR increase >30 bpm (HR increase > 40 bpm in patients <19 years) or HR exceeding 120 bpm in upright position (prior to nitroglycerine administration), within 10 min and in the absence of orthostatic hypotension [3]. note: 'Found by winnow, kev and lev in p013, p026. Claude judged: supports.' - paper: pmid36090156 cited: true text: full license: by-nc-nd verdict: supports section: Patient 1 quote: Given the sustained >30 beats/min increase in her heart rate without a significant blood pressure change during the tilt table test, she met the criteria for a diagnosis of postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid35844239 cited: true text: full license: by verdict: supports section: Materials and Methods > Head-Up Tilt Test quote: 'A response would be considered positive if the cardiac rate was elevated by ≥40 beats·min−1, or if the maximum heart rate reaches the diagnostic criteria (≥130 beats/min for 6- to 12-year-olds, ≥125 beats/min for 12- to 18-year-olds); at the same time, blood pressure changes a little (systolic blood pressure drops <20 mmHg, diastolic blood pressure decreases <10 mmHg) and any two of the following symptoms present during tilting: dizziness/vertigo, thoracic tightness, headache, cardiopalmus, pallor, blurring of vision, weariness, or syncope. Any child with a positive response was diagnosed with POTS.' note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.2. Physiological Predictors for the Oral Rehydration Salts Efficacy in Pediatric POTS quote: Excessive orthostatic tachycardia is the typical hemodynamic standard for both pediatric and adolescent POTS sufferers [63]. The HUTT is a widely accepted test to evaluate POTS in children and adolescents [64,65]. note: 'Found by winnow, kev and lev in p005, p019, p020. Claude judged: supports.' - paper: pmid35620060 cited: true text: full license: by-nc verdict: supports section: Patient 2 quote: 'A tilt table test confirmed POTS: 65 BPM supine HR, 104/72 mm Hg supine BP, 104 BPM standing HR, and 116/84 mm Hg standing BP.' note: 'Found by winnow, kev and lev in p011, p015. Claude judged: supports.' - paper: pmid35463901 cited: true text: full license: by verdict: supports section: Introduction quote: It is associated with an increase in heart rate to >30 bpm (>40 bpm in children/adolescents younger than 19 years) within 10 min of standing (or during a head-up tilt-test to at least 60°) in the absence of orthostatic hypotension (6). note: 'Found by winnow, kev and lev in p015, p007, p018. Claude judged: supports.' - paper: pmid35433537 cited: true text: full license: by verdict: supports section: Abstract > Materials and Methods quote: 53 cases of children aged 5 to 15 years who visited in the Pediatric Syncope Specialist Clinic of The Second Xiangya Hospital of Central South University for unexplained syncope or syncope precursor were diagnosed with POTS by head-up tilt test (HUTT) as the POTS group. note: 'Found by winnow, kev and lev in p002, p010, p012. Claude judged: supports.' - paper: pmid35381331 cited: true text: full license: none verdict: supports section: Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p014, p004, p008. Claude judged: supports.' - paper: pmid35372154 cited: true text: full license: by verdict: supports section: Materials and Methods > Clinical Diagnostic Criteria quote: 'The diagnostic criteria of pediatric POTS included the following: (1) inducements such as a postural change from supine to upright or long-term standing; (2) symptoms of OI elicited by standing upright; (3) standing test or HUTT that meets the standards of positive response; and (4) other causes of OI were excluded. A positive response for POTS in children during the standing test or HUTT was defined as follows: the heart rate is normal at a supine position and increases by ≥ 40 bpm and/or the highest heart rate reaches ≥ 130 bpm in participants aged 6–12 years; or ≥ 125 bpm in adolescents aged 13–18 years, within the first 10 min of the tests.' note: 'Found by winnow, kev and lev in p021, p025, p013. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How should patients be evaluated for POTS? quote: Although not necessary, a head-up tilt table test (for at least 10 min), ideally with continuous beat-to-beat blood pressure monitoring,38 can also be used to diagnose POTS. The tilt table test leads to a slightly greater increase in heart rate than the stand test,39 which increases its diagnostic sensitivity. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Case presentation > Cases 1–7 quote: Postural tachycardia syndrome was diagnosed via tilt table testing, defined as an increased HR of ≥30 beats per min (b.p.m.) within 10 min of assuming an upright posture and in the absence of orthostatic hypotension [blood pressure (BP) fall >20/10 mmHg].8 note: 'Found by winnow, kev and lev in p006, p009. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 4. Postural Orthostatic Tachycardia Syndrome after COVID-19 quote: A 36-year-old woman who recovered from symptomatic SARS-CoV-2 infection in self-isolation started experiencing fatigue, headache, dizziness, chest pain, and orthostatic palpitations one month after the onset of acute infection [44] and was later diagnosed with POTS upon head-up tilt testing. note: 'Found by winnow, kev and lev in p021, p037. Claude judged: supports.' - paper: pmid34604136 cited: true text: full license: by verdict: supports section: Introduction quote: 'A hallmark hemodynamic criterion of POTS in children and adolescents is excessive orthostatic tachycardia: a heart rate (HR) increment ≥40 bpm or an absolute HR ≥130 bpm for children 12 years and younger or ≥125 bpm for adolescents 13–18 years within the first 10 min of the standing test or the head-up tilt test (HUTT) without a drop ≥20 mmHg in systolic blood pressure (SBP) or ≥10 mmHg in diastolic blood pressure (DBP) (2). The HUTT has been widely accepted for the evaluation of POTS in children and adolescents (3, 4).' note: 'Found by winnow, kev and lev in p003, p005, p017. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Case description and results quote: The tilt table test demonstrated the presence of PoTS with a heart rate increase by 60 bpm up to a total of 137 bpm accompanied by symptoms within 10 minutes standing, without orthostatic hypotension. note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid34275953 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34275953. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid33927679 cited: true text: full license: by verdict: supports section: Discussion quote: Autonomic testing in 4 of 6 patients in our series revealed findings potentially compatible with POTS, including 2 patients with both hypertension and tachycardia on HUT, consistent with a hyperadrenergic POTS subtype. POTS is widely considered to be the most common primary autonomic disorder, and is characterized by a heart rate increment that exceeds 30 BPM in adults, or 40 BPM in individuals < 18 years of age, within 10 min of standing or on TTT (5). note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Observa-se elevação sustentada da frequência cardíaca (FC) ≥ 30 bpm (≥40 bpm se <20 anos) ou FC ≥120 bpm nos primeiros 10 minutos em posição ortostática ou durante o tilt test, sem hipotensão ortostática clássica associada. note: 'Found by winnow, kev and lev in p112, p108. Claude judged: supports.' - paper: pmid33886001 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33886001. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p025, p022, p027. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: 'Patient #2' quote: POTS was confirmed by both active standing test and head-up tilt (symptomatic sinus tachycardia >130 beats/min). note: 'Found by winnow, kev and lev in p012, p005. Claude judged: supports.' - paper: pmid33582941 cited: true text: full license: none verdict: supports section: Data and Methods > Head-up tilt test quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33582941. Found by winnow, kev and lev in p009, p013, p014. Claude judged: supports.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: supports section: Case report quote: It was not until March of 2018 and her first consultation with a cardiologist that the patient was diagnosed with POTS after a positive head-up tilt table test. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid33490373 cited: true text: full license: by verdict: supports section: Results quote: There was a highly significant increase in heart rate (p ≤ 0.001) during the first 10 minutes in the drug-free passive phase of tilt without substantial change in the systolic and diastolic blood pressure, qualifying for POTS and mean the difference in heart rate was ≈34 beats per minute. note: 'Found by winnow, kev and lev in p013, p027, p003. Claude judged: supports.' - paper: pmid33352894 cited: true text: full license: by verdict: supports section: 2. Materials and Methods > 2.1. Subjects quote: The POTS was diagnosed if the patient’s heart rate increased by 30 beats per minute (bpm) or measured with over 120 bpm within 5–10 min of head-up tilt (HUT). The test was also accompanied with the measurement of heart rate and blood pressure to confirm the diagnosis. note: 'Found by winnow, kev and lev in p003, p013, p030. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Discussion quote: HUTT may help in difficult clinical scenarios but is mostly used to confirm the clinical diagnosis. A protocol used for tilt-table testing includes a 70° baseline upright tilt for a period of 20 minutes to 30 minutes with continuous heart-rate and blood-pressure monitoring. note: 'Found by winnow, kev and lev in p007, p001, p010. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Introduction quote: Careful patient history can often lead to the diagnosis of POTS, which can then be confirmed by provocative testing such as a head-up tilt table test. note: 'Found by winnow, kev and lev in p013, p004, p008. Claude judged: supports.' - paper: pmid32222376 cited: true text: full license: none verdict: supports section: POTS background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32222376. Found by winnow, kev and lev in p007, p014, p003. Claude judged: supports.' - paper: pmid32112609 cited: true text: full license: by verdict: supports section: SUBJECTS AND METHOD > Study subjects quote: Totally, 100 cases of children and adolescents (50 males and 50 females, with an average age of 11.0 ± 2.4 years), with unexplained syncope or presyncope symptoms, diagnosed as POTS by HUTT were enrolled from Pediatric Specialist Clinic of the Second Xiangya Hospital of Central South University from August 2013 to July 2016. note: 'Found by winnow, kev and lev in p020, p005, p007. Claude judged: supports.' - paper: pmid31888497 cited: true text: full license: by verdict: supports section: Background quote: POTS is the most prevalent form of orthostatic intolerance. It is diagnosed relying on a sustained HR increase of greater than 40 beats per minute or an increase to 120 beats per minute or greater within the first 10 min of tilt, without arterial hypotension. note: 'Found by winnow, kev and lev in p044, p007, p048. Claude judged: supports.' - paper: pmid31780890 cited: true text: full license: by verdict: supports section: Materials and Methods > Diagnosis of POTS quote: 'The diagnosis of POTS was mainly based on the following (Sheldon et al., 2015; Wang et al., 2018, 2019): (1) commonly seen in older children; (2) associated with inducements such as quick position change from supine to upright position, or long-term standing before the appearance of OI symptoms; (3) associated with OI symptoms such as dizziness, headache, fatigue, blurred vision, chest tightness, palpitations, hand tremors, and even syncope; (4) HR increased ≥ 40 bpm or the maximum HR ≥ 130 bpm (in children 6–12 years old) or ≥ 125 bpm (in adolescents 13–18 years old) without orthostatic hypotension (BP decrease > 20/10 mmHg) during the first 10 min of the standing test or BHUTT; and (5) exclusion of other diseases that cause OI symptoms such as cardiovascular diseases, metabolic diseases, neurologic diseases, or psychogenic disorders.' note: 'Found by winnow, kev and lev in p013, p012. Claude judged: supports.' - paper: pmid30560108 cited: true text: full license: by verdict: supports section: Methods quote: When a child with clinical symptoms of OI had an HR increase ≥40 beats/min or an HR of ≥130 bpm (children aged 6–12 years) or ≥125 bpm (adolescents aged 13–18 years) during the initial 10 min of HUTT or standing-up test, without orthostatic hypotension (a BP decrease>20/10 mmHg), the result was defined as a positive response, and a diagnosis of POTS was made (20, 23). note: 'Found by winnow, kev and lev in p006, p003. Claude judged: supports.' - paper: pmid30505831 cited: true text: full license: by verdict: supports section: Abstract quote: Some studies have employed tilt table tests lasting 2–5 min to diagnose one common form of orthostatic intolerance, postural tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p007, p014, p001. Claude judged: supports.' - paper: pmid30372565 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30372565. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid30305583 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30305583. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29451148 cited: true text: full license: by-nc-sa verdict: supports section: METHODS > Technical information quote: Head-up tilt test was applied to diagnose POTS. First, children were kept quietly in the supine position on the tilt table (HUT-821, Beijing Juchi, China) for 10 min, and their HR, blood pressure, and electrocardiograph were recorded by a Dash 2000 Multi-lead Physiological Monitor (General Electric, New York, USA). note: 'Found by winnow, kev and lev in p010, p007. Claude judged: supports.' - paper: pmid29391028 cited: true text: full license: by verdict: supports section: Results > Case reports quote: At age 31, a 70-degree head-up tilt table test showed a 61 bpm increase in HR from 65 bpm supine to a peak of 126 bpm at 10 min, with reproduction of her typical orthostatic symptoms, but without orthostatic hypotension, thus consistent with POTS. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Investigations quote: The tilt table test demonstrated the presence of hyperadrenergic POTS (increase in heart rate >30 beats/min, rise in systolic blood pressure ≥10 mm Hg and serum norepinephrine level ≥600 pg/mL). note: 'Found by winnow, kev and lev in p006, p013. Claude judged: supports.' - paper: pmid28674628 cited: true text: full license: by-nc verdict: supports section: Discussion quote: For obvious reasons, patients with POTS demonstrated greatest increase in HR during HUT, outperforming that of VVS positive and negative HUT but the difference between patients with VVS and negative HUT was also significant. However, although orthostatic increase in HR in POTS is pathognomonic for this syndrome, less is known about chronotropic response in patients with VVS compared with normal subjects. note: 'Found by winnow, kev and lev in p018, p023. Claude judged: supports.' - paper: pmid28554964 cited: true text: full license: by verdict: supports section: Materials and Methods > Postural tachycardia syndrome quote: Potential POTS patients for the study were selected based on referral to our clinic for chronic orthostatic intolerance lasting longer than 6 months; diagnosis was confirmed in our laboratory by means of a screening 70° upright tilt test (HUT). note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid28286774 cited: true text: full license: by verdict: supports section: 2. Materials and Methods > 2.3. Cardiovascular Reflex Tests > 2.3.5. HUT quote: POTS was defined as a sustained HR rise of at least 30 bpm or a HR of at least 120 bpm in the first 10 min of tilt, without concomitant OH [23]. note: 'Found by winnow, kev and lev in p012, p025, p026. Claude judged: supports.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: supports section: Methods > Diagnostic criteria of postural tachycardia syndrome and classic vasovagal syncope quote: The test was diagnostic when patients demonstrated a typical prodrome (such as palpitation, nausea, dizziness, lightheadedness, or intense perspiration) reproducing previous events experienced and/or precipitated syncope, and the haemodynamic parameters met the diagnostic criteria of POTS or VVS, respectively.4,11,14 Briefly, POTS was defined as characteristic symptoms of orthostatic intolerance (lightheadedness, dizziness, and/or discomfort) with a maximal and persistent heart rate increase of >30/min (or ≥40/min for those aged ≤19 years) or tachycardia of >120/min in standing position, and the absence of orthostatic hypotension, i.e. max systolic/diastolic BP drop was <20/10 mmHg on head-up tilt.2,11 note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid27631244 cited: true text: full license: by verdict: supports section: Discussion quote: The diagnosis of POTS can be readily made by tilt-table assessment finding a pulse greater than 120 beats/minute or an elevation of pulse of 30 BPM in the first 10 minutes of elevation into an upright position, which is different than the fall of blood pressure as seen in vasovagal syncope under the same conditions. note: 'Found by winnow, kev and lev in p009, p013, p020. Claude judged: supports.' - paper: pmid27413567 cited: true text: full license: by verdict: supports section: Abstract quote: According to the tilt table test the patient was diagnosed with POTS. note: 'Found by winnow, kev and lev in p007, p001, p006. Claude judged: supports.' - paper: pmid26645307 cited: true text: full license: by verdict: supports section: Discussion quote: In this pilot study of adolescents with chronic nausea and POTS confirmed by abnormal HUT test, the use of HIRREM was associated with the increase in heart rate variability in the time domain (SDNN) and BRS in the frequency domain (HF alpha). note: 'Found by winnow, kev and lev in p008, p016. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Clinical Presentation of POTS > Diagnostic Criteria quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid25917768 cited: true text: full license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25917768. Found by winnow, kev and lev in p008, p003, p004. Claude judged: supports.' - paper: pmid25811760 cited: true text: full license: by verdict: supports section: Materials and Methods > Head-up test and head-up tilt test > Head-up tilt test (HUTT) quote: During the test, if an increase in heart rate ≥ 40 beats/min or the maximum heart rate ≥ 120 beats/min was accompanied by two of the following symptoms such as dizziness or vertigo, chest tightness, headache, palpitations, a change in paleness, blurred vision, fatigue, morning discomfort, or syncope during tilt, the diagnosis of POTS was made[20]. note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid25510829 cited: true text: full license: none verdict: supports section: Methods > Subjects quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25510829. Found by winnow, kev and lev in p008, p001, p024. Claude judged: supports.' - paper: pmid25180969 cited: true text: full license: by verdict: supports section: Materials and Methods > Autonomic function tests quote: Based on the response pattern to HUT, patients were classified as OH, NCS, or POTS. note: 'Found by winnow, kev and lev in p001, p011. Claude judged: supports.' - paper: pmid25002851 cited: true text: full license: by verdict: supports section: Materials and methods > Subjects quote: POTS was identified during upright tilt table testing to 70° by signs and symptoms of OI and an excessive increase in HR within 10 min of head-up tilt (HUT) (Low et al., 1995; Raj, 2006; Medow and Stewart, 2007). note: 'Found by winnow, kev and lev in p008, p022, p024. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Diagnostic Evaluation of Possible POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p073, p075, p026. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Methods > Subjects quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p006, p001, p022. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Both active standing tests and HUTT are sensitive for the diagnosis of POTS [3]. note: 'Found by winnow, kev and lev in p006, p008, p009. Claude judged: supports.' - paper: pmid23802020 cited: true text: full license: by-nc verdict: supports section: 'MATERIALS AND METHODOLOGY:' quote: Subjects who presented to the Cleveland Clinic from January to December 2007 for evaluation of symptoms of orthostatic intolerance and subsequently diagnosed with POTS on head-up Tilt test in the Syncope Clinic were included. note: 'Found by winnow, kev and lev in p002, p008. Claude judged: supports.' - paper: pmid23729158 cited: true text: full license: none verdict: supports section: Schematic design of the study > Definition of different variables quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23729158. Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid23390443 cited: true text: full license: by-nc verdict: supports section: Abstract > Methods quote: Diagnosis of POTS was based on chronic day-to-day orthostatic intolerance symptoms as well as excessive tachycardia during the TTT. note: 'Found by winnow, kev and lev in p002, p004, p006. Claude judged: supports.' - paper: pmid23270259 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23270259. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Case presentation quote: A head-up tilt test reproduced the same orthostatic symptoms, with an increased sinus rate and stable blood pressure (Table 2). The increase in heart rate without orthostatic hypotension along with the accompanying symptoms confirmed the presence of POTS. note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid22689545 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22689545. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid21977261 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p001, p017, p019. Claude judged: supports.' - paper: pmid20309394 cited: true text: full license: by-nc-nd verdict: supports section: Methods quote: The diagnosis of POTS was based on clinical history, clinical examination and a positive (POTS pattern) head up tilt test (HUTT). The HUTT criterion for diagnosing POTS was an absolute heart rate >120 bpm or an increase by > 30bpm within the first ten minutes of an upright tilt. note: 'Found by winnow, kev and lev in p008, p002, p014. Claude judged: supports.' - paper: pmid20167544 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20167544. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid19264762 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19264762. Found by winnow, kev and lev in p002, p003. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: HUT and Evaluation of Adrenergic Function quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid11227722 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11227722. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid10406593 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 10406593. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid40584422 cited: true text: full license: by verdict: partial section: Discussion > Physiological mechanisms of POTS and interpretation quote: Schondorf and Low conducted a review of patients aged 20–51 who exhibited POTS during HUTT. note: 'Found by winnow, kev and lev in p003, p028. Claude judged: partial.' - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: partial section: CBF in OI > CBF in POTS quote: "Novak et al\n3\n studied diagnostic metrics for assessing multiple forms of OI during head‐up tilt and\ \ outlined the crucial importance of measuring TCD in conditions with OI. CBv, measured in the middle cerebral\ \ artery (MCA), served as a more accurate tool in differentiating POTS from other forms of tachycardia." note: 'Found by winnow, kev and lev in p029, p036. Claude judged: partial.' - paper: pmid39664665 cited: true text: full license: by-nc-nd verdict: partial section: Case report > Background quote: This BP and HR pattern seen during TT was consistent with a diagnosis of orthostatic tachycardia and VVS with VASIS type 1 pattern1 (Figure 1A). note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid37519618 cited: true text: full license: by verdict: partial section: Abstract quote: During her tilt table training, she started having episodes of sinus tachycardia associated with fatigue, dizziness, headache, palpitations, and presyncope with no orthostatic hypotension, after achieving 60 degrees of head tilt. After ruling out the common causes of tachycardia and syncope, a diagnosis of POTS was established. note: 'Found by winnow, kev and lev in p001, p005, p007. Claude judged: partial.' - paper: pmid36873318 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: As previously reported, α1AR and β1AR co-immunization produced an enhanced postural HR increase in the absence of significant BP change in the rabbit, confirming a POTS-like phenotype of this model.9 note: 'Found by winnow, kev and lev in p022, p017. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Case presentation quote: AST (Figure 2A) and head-up tilt test (Figure 2B) demonstrated an increase in heart rate in excess of 40 bpm. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid35725868 cited: true text: full license: none verdict: partial section: Case report quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid35680184 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35680184. Found by winnow, kev and lev in p001, p003. Claude judged: partial.' - paper: pmid35557616 cited: true text: full license: by verdict: partial section: Case Presentation quote: He was subsequently referred to a neuro-autonomic specialist for a formal tilt table test, which revealed a heart rate increase of 60 beats/min immediately after tilt, and then remained 45–58 beats above baseline, with a maximum heart rate of 136 beats/min, for 8 min of tilt. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid35097001 cited: true text: full license: by verdict: partial section: Abstract quote: 'Overall, 2,343 (48.1%) showed positive responses as follows: 1,260 (25.9%) with the mixed type, 34 (0.7%) with the cardioinhibitory type, 580 (11.9%) with the vasodepressor type, 179 (3.7%) with postural tachycardia syndrome (POTS), and 290 (6.0%) with orthostatic hypotension (OH).' note: 'Found by winnow, kev and lev in p015, p004, p016. Claude judged: partial.' - paper: pmid35056406 cited: true text: full license: by verdict: partial section: 3. Results > Case Example quote: The tilt test provoked her usual orthostatic symptoms, along with POTS, hypocapnia during standing, and a severe 40% decline in cerebral blood flow. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: partial section: Results > Tilt > Centering Point, Response Range quote: Gmax and the response range remained unchanged with tilt in control, is reduced in POTS, and further reduced in POTS when tilted. Additional key features of POTS include left lateral and downwards shifts of centering points and operating points and decreased response range with tilt. note: 'Found by winnow, kev and lev in p043, p032, p035. Claude judged: partial.' - paper: pmid33114659 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by a marked increase in heart rate (>30 beats per minute) or tachycardia (>120 beats per minute) upon standing or when exposed to a passive gravitational stimulus (i.e., head-up tilt) without orthostatic hypotension. note: 'Found by winnow, kev and lev in p035, p002, p018. Claude judged: partial.' - paper: pmid32880754 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Materials and Methods quote: We analyzed the raw data of the HUT tests individually and made group-level comparisons. The subjects included in the POTS group met the current criteria for POTS (Sheldon et al., 2015). note: 'Found by winnow, kev and lev in p004, p010, p014. Claude judged: partial.' - paper: pmid32669178 cited: true text: abstract license: none verdict: partial section: Abstract > Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32669178. Found by winnow, kev and lev in p002, p003. Claude judged: partial.' - paper: pmid32078525 cited: true text: abstract license: none verdict: partial section: Abstract > Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32078525. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: 'Results > Hemodynamic, autonomic function tests and catecholamines:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p023, p024, p034. Claude judged: partial.' - paper: pmid30755882 cited: true text: full license: by-nc-nd verdict: partial section: CASE 4 quote: She had a positive tilt table test with documented hypotension and tachycardia with symptoms. The diagnosis of POTS syndrome associated with hypermobility syndrome was considered in this patient. note: 'Found by winnow, kev and lev in p003, p020, p023. Claude judged: partial.' - paper: pmid30197684 cited: true text: full license: by verdict: partial section: Materials and Methods > Subjects quote: The POTS patients showed a rise in heart rate (HR) >40 bpm in first 10 mins of tilt as displayed in Table 3. note: 'Found by winnow, kev and lev in p031, p016. Claude judged: partial.' - paper: pmid25748400 cited: true text: abstract license: none verdict: partial section: Abstract > Result quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25748400. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid25071706 cited: true text: full license: by verdict: partial section: Results > Autonomic testing quote: Head-up tilt table testing showed an increase in heart rate of PoTS patients with a median of 38.99 bpm (30.00–43.00). This was significantly higher than in controls (p = 0.000), who showed a median in heart rate increase by 15.00 bpm (12.00–25.00). note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid24601948 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24601948. Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid22739942 cited: true text: abstract license: none verdict: partial section: Abstract > Material And Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22739942. Found by winnow, kev and lev in p003, p004. Claude judged: partial.' - paper: pmid16176538 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16176538. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid8423877 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 8423877. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - active_stand_test - evidence_for - pots papers: 43 evidence: - paper: pmid41713697 cited: true text: full license: by verdict: supports section: Methods quote: The highest standing HR was used to calculate ΔHR (difference from supine), and symptoms during the test were documented. Patients with ΔHR ≥40 bpm were classified as POTS, while those with ΔHR <40 bpm but experiencing orthostatic symptoms were classified as COI. note: 'Found by winnow, kev and lev in p014, p002, p019. Claude judged: supports.' - paper: pmid41584279 cited: true text: full license: by verdict: supports section: Methods > Inclusion criteria quote: Additionally, studies that detailed the use of objective tests, such as the head-up tilt or active standing test, for assessment and reported POTS diagnoses confirmed by these tests were also included. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid40970182 cited: true text: full license: by verdict: supports section: Materials and methods > Procedures > Passive standing test quote: Patients were diagnosed with POTS if they exhibited a sustained pulse increase of more than 30 bpm (or exceeding 120 bpm) within 10 min of standing, accompanied by clinical signs of orthostatic intolerance persisting for at least 3 months, in the absence of orthostatic hypotension (Vernino et al., 2021). note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid40694349 cited: true text: full license: by verdict: supports section: Discussion quote: While tilt table tests are more sensitive than active standing for detecting POTS,27,28 they may also reduce specificity, increasing false positives. note: 'Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Methods quote: POTS was defined by an increase in HR of more than 30 beats/min within 10 minutes of active standing, without a significant drop in systolic BP (<20 mm Hg), and accompanied by symptoms resolving with recumbency—such as lightheadedness, fatigue, nausea, palpitations, generalized weakness, blurred vision, exercise intolerance, or headache.8,10,13 note: 'Found by winnow, kev and lev in p013, p032. Claude judged: supports.' - paper: pmid40533427 cited: true text: full license: by verdict: supports section: Body quote: The confirmed diagnosis was based on international criteria, including a sustained heart rate increase of at least 30 beats per minute or at least 40 beats per minute in adolescents (16–19 years of age) during a 10‐minute active standing test or head‐up tilt table test, the absence of orthostatic hypotension, and unexplained symptoms of orthostatic intolerance lasting at least three months. note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid40432440 cited: true text: full license: by verdict: supports section: Methods quote: The diagnosis of POTS was made in the presence of a sustained increase in heart rate ≥ 30 bpm (at least two measurements 1 minute apart) during 10 minutes of standing in the absence of orthostatic hypotension. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid40310134 cited: true text: full license: by verdict: supports section: 2. Materials and Methods > 2.1. Diagnostic Methods > 2.1.5. Classification of TTT Responses quote: POTS was diagnosed based on standardized standing test criteria. The diagnostic threshold included an HR increase of at least 40 bpm within 10 min of assuming an upright posture. note: 'Found by winnow, kev and lev in p028, p033. Claude judged: supports.' - paper: pmid40125494 cited: true text: full license: by verdict: supports section: Discussion quote: To evaluate for POTS, an active stand test or a formal upright tilt table test may be performed.2 note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p001, p025, p003. Claude judged: supports.' - paper: pmid38074226 cited: true text: full license: by-nc-sa verdict: supports section: Case presentation quote: The symptoms subsided rapidly within one minute of lying down in a supine position. These findings are indicative of POTS. note: 'Found by winnow, kev and lev in p010, p015. Claude judged: supports.' - paper: pmid38033543 cited: true text: full license: by verdict: supports section: Materials and methods > Diagnosis of POTS quote: 'The positive criteria for POTS in the associated tests included the following: (1) normal HR when lying on the back; (2) within the first 10 min after standing up in standing test or tilted in HUTT an increase in HR (≥ 40 bpm) and/or a maximum HR ≥ 130 and ≥ 125 bpm for ages 6–12 and 13–18 years, respectively; (3) with out significant orthostatic hypotension (decline of BP < 20/10 mmHg) (Medow et al., 2017; Wang et al., 2018).' note: 'Found by winnow, kev and lev in p011, p021. Claude judged: supports.' - paper: pmid37391116 cited: true text: full license: none verdict: supports section: Results > Participants with PASC fulfilling POTS diagnosis quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid37378164 cited: true text: full license: by verdict: supports section: Introduction quote: Furthermore, the following diagnostic criteria used to assist in identifying POTS include a sustained heart rate elevation of at least 30 bpm in adults and at least 40 bpm in teens 12-19 years of age from supine to standing position during a 10-min stand test or a tilt table test. note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid37255912 cited: true text: full license: by verdict: supports section: Abstract quote: An Active Stand test was performed on the day of attendance, identifying Postural Orthostatic Tachycardia Syndrome (POTS). note: 'Found by winnow, kev and lev in p001, p006, p007. Claude judged: supports.' - paper: pmid36818521 cited: true text: full license: by-nc-nd verdict: supports section: Methods > Active 10-min Standing Test quote: POTS was diagnosed based on an increase in heart rate of ≥30 beats/min,23 with symptoms of OI. In addition, in the present study, an actual heart rate of ≥120 beats/min, indicating accentuated sympathetic activity, with symptoms of OI during the test was also considered to occur due to POTS.12 note: 'Found by winnow, kev and lev in p012, p015, p018. Claude judged: supports.' - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: We found that according to the results of the active orthostatic test, 37.5% of patients with ME/CFS met the diagnostic criteria for POTS. note: 'Found by winnow, kev and lev in p015, p046. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How should patients be evaluated for POTS? quote: Heart rate and blood pressure must be measured when the patient has been supine for 5–10 minutes to allow fluid equilibration, and then after standing for 1 minute, 3 minutes, 5 minutes, 8 minutes and 10 minutes.5 To diagnose excessive orthostatic tachycardia (required for POTS), patients should have a sustained heart rate increase of at least 30 beats/min (for adults) or at least 40 beats/min (for patients aged 12–19 yr) on at least 2 of the readings taken when standing. note: 'Found by winnow, kev and lev in p026, p027. Claude judged: supports.' - paper: pmid35224842 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION > OI across the hypermobility spectrum > Comparison of hemodynamic responses and diagnosis of POTS during HUT and active stand quote: The active stand test was able to detect POTS at a greater rate than HUT, supporting the fact that active stand is a reasonable clinical test to use in this population. note: 'Found by winnow, kev and lev in p051, p034. Claude judged: supports.' - paper: pmid34987818 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Following the absence of abnormal echocardiogram findings, thyroid dysfunction, vasculitis and rhythm disturbances, a possible diagnosis of POTS was established with a positive active stand test and 10-min walk test. note: 'Found by winnow, kev and lev in p007, p001, p015. Claude judged: supports.' - paper: pmid34055686 cited: true text: full license: by verdict: supports section: Abstract quote: Furthermore, the maximum ΔHR (ΔHRmax) and ΔHR at 5 and 10 min in the afternoon and evening standing tests yielded moderate predictive values for the POTS diagnosis. The external validation test showed that the afternoon ΔHRmax ≥30 bpm to diagnose POTS yielded sensitivity, specificity, and accuracy of 85, 71.4, and 78%, respectively, and the evening ΔHRmax ≥25 bpm yielded sensitivity, specificity, and accuracy of 85, 76.2, and 80.5%, respectively. note: 'Found by winnow, kev and lev in p003, p016, p017. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Diskussion quote: Am Fallbeispiel 2 können wir zeigen, dass Kinder nach SARS-CoV-Infektion eine chronische Regulationsstörung des autonomen Nervensystems mit einem POTS entwickeln können, welches in einem einfachen aktiven Stehtest mit kontinuierlicher EKG-Registrierung nachweisbar ist. note: 'Found by winnow, kev and lev in p007, p010. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: 'Patient #2' quote: POTS was confirmed by both active standing test and head-up tilt (symptomatic sinus tachycardia >130 beats/min). note: 'Found by winnow, kev and lev in p010, p012, p015. Claude judged: supports.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Postural tachycardia syndrome (POTS) is defined in adults by orthostatic intolerance symptoms plus an excessive increase in heart rate exceeding 30 beats/min within 10 minutes of standing or upright tilt.3 Systolic arterial pressure (SAP) is maintained and may increase.4 note: 'Found by winnow, kev and lev in p005, p043. Claude judged: supports.' - paper: pmid31780890 cited: true text: full license: by verdict: supports section: Materials and Methods > Diagnosis of POTS quote: 'The diagnosis of POTS was mainly based on the following (Sheldon et al., 2015; Wang et al., 2018, 2019): (1) commonly seen in older children; (2) associated with inducements such as quick position change from supine to upright position, or long-term standing before the appearance of OI symptoms; (3) associated with OI symptoms such as dizziness, headache, fatigue, blurred vision, chest tightness, palpitations, hand tremors, and even syncope; (4) HR increased ≥ 40 bpm or the maximum HR ≥ 130 bpm (in children 6–12 years old) or ≥ 125 bpm (in adolescents 13–18 years old) without orthostatic hypotension (BP decrease > 20/10 mmHg) during the first 10 min of the standing test or BHUTT; and (5) exclusion of other diseases that cause OI symptoms such as cardiovascular diseases, metabolic diseases, neurologic diseases, or psychogenic disorders.' note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: supports section: Method > Study subjects quote: For the diagnosis of POTS, we checked blood pressure and heart rate at supine rest and 0, 1, 3, 5, and 10 min after standing. Two consecutive tests were conducted, usually in the afternoon and early the next morning, to increase the sensitivity.8 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid31118385 cited: true text: full license: by-nc-nd verdict: supports section: Case Report quote: Active standing tests showed a significant heart rate increase (68 bpm during supine position, 109 bpm during standing), while her blood pressure was 122/78 mmHg in the spine position and 129/77 mmHg while standing. These findings were consistent with POTS (3). note: 'Found by winnow, kev and lev in p005, p006. Claude judged: supports.' - paper: pmid30560108 cited: true text: full license: by verdict: supports section: Methods quote: When a child with clinical symptoms of OI had an HR increase ≥40 beats/min or an HR of ≥130 bpm (children aged 6–12 years) or ≥125 bpm (adolescents aged 13–18 years) during the initial 10 min of HUTT or standing-up test, without orthostatic hypotension (a BP decrease>20/10 mmHg), the result was defined as a positive response, and a diagnosis of POTS was made (20, 23). note: 'Found by winnow, kev and lev in p006, p003. Claude judged: supports.' - paper: pmid30505831 cited: true text: full license: by verdict: supports section: Introduction quote: The various consensus criteria for POTS all require a heart rate (HR) increase of at least 30 beats per minute over the course of 10 min upright for adults (or at least 40 bpm for those 12–19 years) compared to measurements in the supine position (12–14). These HR changes can be assessed using either passive or active standing maneuvers, or head-up tilt testing (15–21). note: 'Found by winnow, kev and lev in p006, p017. Claude judged: supports.' - paper: pmid26033944 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Comparative studies on the active standing test and HUTT have discovered that both methods have similar sensitivity, and that the active standing test has even higher specificity than HUTT (79% vs 23%) when increased heart rate is ≥30 bpm, as a POTS diagnostic criterion. note: 'Found by winnow, kev and lev in p030, p006, p021. Claude judged: supports.' - paper: pmid25474569 cited: true text: full license: by verdict: supports section: Subjects and Methods > Upright Test quote: 'The criteria for a positive reaction (POTS) were as follows: the HR increased by over 40 beats/min or the maximum HR was over 120 beats/min, and the patients had at least one of the following symptoms during the ten minutes standing: dizziness or fainting, chest tightness, headache, palpitations, blurred vision, fatigue or syncope for at least 3 months [11], [19]–[22].' note: 'Found by winnow, kev and lev in p002, p012, p026. Claude judged: supports.' - paper: pmid24227635 cited: true text: full license: none verdict: supports section: Methods > Subjects quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24227635. Found by winnow, kev and lev in p008, p014. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Both active standing tests and HUTT are sensitive for the diagnosis of POTS [3]. note: 'Found by winnow, kev and lev in p008, p009. Claude judged: supports.' - paper: pmid23283362 cited: true text: full license: none verdict: supports section: METHODS > Subjects quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23283362. Found by winnow, kev and lev in p010, p028. Claude judged: supports.' - paper: pmid42387884 cited: true text: full license: by verdict: partial section: RESULTS quote: Overall, 45/221 (20%) of patients fulfilled the haemo-dynamic algorithm criteria for a positive NLT (at least 2 consecutive HR values exceeding the diagnostic threshold of an increase ≥ 30 bpm, no systolic blood pressure decrease over 20 mmHg within the first 3 min of standing) and reported orthostatic symptoms during the test. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid41163092 cited: true text: full license: by-nc-nd verdict: partial section: Results quote: Over 10 min, the HR increased by an average of 10 ± 3 bpm, and systolic BP dropped by 1.3 ± 0 0.4 mmHg. A total of 18 patients (8.5%) met the criteria for POTS. note: 'Found by winnow, kev and lev in p023, p027, p003. Claude judged: partial.' - paper: pmid39592549 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39592549. Found by winnow, kev and lev in p003, p002. Claude judged: partial.' - paper: pmid38176772 cited: true text: full license: none verdict: partial section: Methods > Clinical data collection quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38176772. Found by winnow, kev and lev in p015, p010. Claude judged: partial.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: partial section: Abstract > Case summary quote: Evaluation with a NASA Lean Test revealed marked orthostatic tachycardia, as well as delayed orthostatic hypotension. Given her COVID-19 illness 4 months prior, PASC involving autonomic dysfunction was diagnosed. note: 'Found by winnow, kev and lev in p002, p020, p021. Claude judged: partial.' - paper: pmid35733987 cited: true text: full license: by verdict: partial section: Results quote: POTS is associated with a rapid increase in heart rate that occurs within 10 min upon standing. In this study, heart rate significantly increased as evidenced by a high delta change between heart rate measurement taken in the supine position and after 10 min of standing (Figure 3C). note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid35673757 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35673757. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35035423 cited: true text: full license: by verdict: partial section: 'METHODS > Head up tilt test protocol:' quote: In the same setting if the patient’s heart rate increased by 30 beats a minute (bpm) or more (40bpm in those aged 12 to 19) usually within 10 minutes of standing. And also if that increase continued for more than 30 seconds accompanied by other symptoms were suggestive of POTS. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid24495468 cited: true text: full license: none verdict: partial section: RESULTS > Baseline Characteristics quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24495468. Found by winnow, kev and lev in p011, p018. Claude judged: partial.' - edge: - autonomic_autoantibody_assay - evidence_for - autoimmune_evidence papers: 22 evidence: - paper: pmid38736760 cited: true text: full license: by verdict: supports section: Conclusions quote: However, the detection of several types of autoantibodies and the improvement of the clinical picture after plasma exchange therapy in this case points to an autoimmune pathogenesis. note: 'Found by winnow, kev and lev in p012, p020, p022. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.2. Cholinergic Receptors quote: Watarai et al. provided further evidence of the autoimmune basis of POTS by examining the presence of AAbs in POTS patients and patients with neurally mediated syncope. mAChR AAbs were found in 10 of the POTS patients. note: 'Found by winnow, kev and lev in p016, p021, p022. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Discussion quote: In this case the diagnostic work-up of PoTS led to the diagnosis of autoimmune-mediated neuropathic PoTS as a crossroad of PoTS, SFN and autoimmunity. The characterisation of autoantibodies against adrenergic and muscarinic receptors is nowadays performed in specialized laboratories with the use of life-based bioassays on cardiomyocytes confirming the functional role of these autoantibodies [34]. note: 'Found by winnow, kev and lev in p023, p009, p014. Claude judged: supports.' - paper: pmid34409582 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34409582. Found by winnow, kev and lev in p001, p004, p006. Claude judged: supports.' - paper: pmid34275953 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34275953. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29618472 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Methods and Results quote: Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. note: 'Found by winnow, kev and lev in p016, p023, p002. Claude judged: supports.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: supports section: Discussion quote: These contractile responses were observed with sera/IgG from each of the POTS patients providing strong evidence that this effect was mediated by circulating autoantibodies to their respective target receptors and not from stray ligands in the sample (eg, norepinephrine). note: 'Found by winnow, kev and lev in p017, p021, p022. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Results quote: AR-modulating autoantibody activity was also higher in patients with POTS vs those without and directly correlated with heart rate changes. note: 'Found by winnow, kev and lev in p004, p025, p014. Claude judged: partial.' - paper: pmid40432440 cited: true text: full license: by verdict: partial section: Abstract quote: Autoantibody concentration against ADRA1, ADRB1, ADRB2, and M4R were not significantly different between the groups. Autoimmune mechanisms may lead to abnormal regulation of the renin-angiotensin-aldosterone system and may contribute to the pathophysiology of POTS. note: 'Found by winnow, kev and lev in p001, p010, p029. Claude judged: partial.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 2. COVID-19-Related POTS > 2.2. Presumed Mechanism for COVID-19-Related POTS > 2.2.2. Hyperadrenergic Reaction quote: Autoantibodies to G-protein-coupled receptors were measured in a study of 31 patients with persistent long COVID-19 symptoms, and autoantibodies to β2-AR, α1-AR, angiotensin II AT1-receptor, nociceptin-like opioid receptor, and muscarinic M2-receptor were identified [33]. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 6. Diagnosis quote: Levels of G-AChRs antibody titers >1.0 nmol/L are quite specific for autoimmune autonomic ganglionopathy (74). note: 'Found by winnow, kev and lev in p020. Claude judged: partial.' - paper: pmid35269395 cited: true text: full license: by verdict: partial section: Abstract quote: The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34117922 cited: true text: full license: by verdict: partial section: Inflammatory biomarkers in postural orthostatic tachycardia syndrome with elevated g-protein-coupled receptor autoantibodies quote: All patients in the study (n = 34) had been diagnosed with POTS according to established criteria and had known elevations of autoantibodies to alpha-1 adrenergic (100%) and anti-muscarinic cholinergic receptors (55.9%). These G-protein-coupled receptors have previously been found to be elevated in POTS patients in a number of prior studies investigating the possible autoimmune basis of POTS. note: 'Found by winnow, kev and lev in p002, p004, p009. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: Abstract quote: A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. note: 'Found by winnow, kev and lev in p010, p001, p007. Claude judged: partial.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: partial section: Conclusions quote: Serum‐mediated ADRA1A activity is associated with the severity of orthostatic symptoms in patients with POTS, independently of the orthostatic hemodynamic response. These findings provide new insights into the pathophysiology of POTS and prompt further research on possible autoimmune involvement in patients with POTS. note: 'Found by winnow, kev and lev in p016, p018, p039. Claude judged: partial.' - paper: pmid32743496 cited: true text: full license: by verdict: partial section: Discussion quote: We found that as a group, POTS patients had greater agonist activity at both α1AR and β1AR. These responses reinforce previous studies identifying the presence of AAb directed towards cardiovascular G protein-coupled receptors (GPCR) in some participants with POTS. note: 'Found by winnow, kev and lev in p027, p028, p001. Claude judged: partial.' - paper: pmid31547756 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: There is an emerging body of evidence that suggests an autoimmune basis for POTS.3 Several studies have investigated the presence of autoantibodies in POTS and their effects on cholinergic and adrenergic receptors.3 note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Methods and Results quote: We also evaluated serum levels of autoantibodies against 4 subtypes of G‐protein coupled adrenergic receptors and 5 subtypes of G‐protein coupled muscarinic acetylcholine receptors by ELISA. note: 'Found by winnow, kev and lev in p002, p013, p018. Claude judged: partial.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Several etiologies are suggested in patients with POTS; however, a considerable number of patients with POTS seem to have antibodies to one or more of the ARs according to recent studies.2, 3 Among the autoantibodies reported in POTS, approximately half of the patients had autoantibodies to β2AR in previous studies.2, 3 note: 'Found by winnow, kev and lev in p011, p016. Claude judged: partial.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: And, we examined potential immune‐mediation of POTS by evaluating autoantibodies against gAChR, which have been implicated in both POTS and POTS‐associated autonomic dysfunction. note: 'Found by winnow, kev and lev in p003, p015, p017. Claude judged: partial.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: partial section: Discussion quote: For the primary objective, we found that antiadrenergic α1AR autoantibody activity was evident in POTS, while the VVS subjects were not different from normal subjects. note: 'Found by winnow, kev and lev in p018, p021, p025. Claude judged: partial.' - paper: pmid23002038 cited: true text: full license: none verdict: partial section: 4 Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23002038. Found by winnow, kev and lev in p019, p021. Claude judged: partial.' - edge: - autonomic_autoantibody_assay - evidence_for - pots papers: 18 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Results > AR autoantibody activity in patients with POTS quote: 'To assess this, we compared AR autoantibody activity in plasma from 8 patients with POTS and 8 without at 30 days post-HSCT. Patients with POTS had significantly higher median activity than those without (25.6 AU [Q1-Q3: 23.8-26.2 AU] vs 22.0 AU [Q1-Q3: 20.5-23.3 AU]; P = 0.006), and this activity significantly correlated with the change in HR upon standing (r = 0.653; P = 0.006) (Figure 4, Table 3).' note: 'Found by winnow, kev and lev in p004, p025, p014. Claude judged: partial.' - paper: pmid40432440 cited: true text: full license: by verdict: partial section: Discussion quote: Dubey et al reported increased presence of muscarinic receptor type 1 and 2 antibodies in POTS patients compared to controls (study enrolled 16 POTS patients and 20 controls) [19]. note: 'Found by winnow, kev and lev in p001, p029, p037. Claude judged: partial.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 2. COVID-19-Related POTS > 2.2. Presumed Mechanism for COVID-19-Related POTS > 2.2.2. Hyperadrenergic Reaction quote: Autoantibodies to G-protein-coupled receptors were measured in a study of 31 patients with persistent long COVID-19 symptoms, and autoantibodies to β2-AR, α1-AR, angiotensin II AT1-receptor, nociceptin-like opioid receptor, and muscarinic M2-receptor were identified [33]. Increased AR antibodies due to COVID-19 infection may lead to vasoconstriction and tachycardia, which has been proposed as a possible mechanism in POTS [35]. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.2. Cholinergic Receptors quote: Watarai et al. provided further evidence of the autoimmune basis of POTS by examining the presence of AAbs in POTS patients and patients with neurally mediated syncope. mAChR AAbs were found in 10 of the POTS patients. note: 'Found by winnow, kev and lev in p016, p021, p022. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 6. Diagnosis quote: The measurement of inflammation or autoimmunity markers is a reasonable option in the context of clinical suspicion of POTS associated with SARS-CoV-2 (41, 66). note: 'Found by winnow, kev and lev in p020. Claude judged: partial.' - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Introduction quote: Indeed, a variety of antibodies against adrenergic α - and β -, angiotensin II type 1, muscarinic 1–5 and nociceptin-like receptors have been detected in series of PoTS patients but not in control sera [[22], [23], [24]]. note: 'Found by winnow, kev and lev in p009, p023. Claude judged: partial.' - paper: pmid34409582 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34409582. Found by winnow, kev and lev in p001, p004. Claude judged: partial.' - paper: pmid34275953 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34275953. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34117922 cited: true text: full license: by verdict: partial section: Inflammatory biomarkers in postural orthostatic tachycardia syndrome with elevated g-protein-coupled receptor autoantibodies quote: All patients in the study (n = 34) had been diagnosed with POTS according to established criteria and had known elevations of autoantibodies to alpha-1 adrenergic (100%) and anti-muscarinic cholinergic receptors (55.9%). These G-protein-coupled receptors have previously been found to be elevated in POTS patients in a number of prior studies investigating the possible autoimmune basis of POTS. note: 'Found by winnow, kev and lev in p002, p004. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 2. Materials and Methods > 2.1. Patients quote: In contrast to our previous report that found the most significant elevation of the alpha 1 adrenergic receptor (AdrR A1) autoantibody (ab) in 89% (49/55) of POTS patients, all thirty-four patients in this study had elevated AdrR A1 Abs (Figure 1). note: 'Found by winnow, kev and lev in p010, p031. Claude judged: partial.' - paper: pmid32743496 cited: true text: full license: by verdict: partial section: Abstract > Results quote: Mean activity values were greater in the POTS vs. Controls for α1AR-AAb (6.2 ​± ​1.2 vs. 5.3 ​± ​1.0; P ​< ​0.001) and β1AR-AAb (5.7 ​± ​1.8 vs. 4.1 ​± ​0.9; P ​< ​0.001). Compared to controls, more POTS patients were positive for α1AR-AAb activity (22% vs 4%; P ​= ​0.007) and β1AR-AAb activity (52% vs. 2%; P ​< ​0.001). note: 'Found by winnow, kev and lev in p027, p028, p003. Claude judged: partial.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: We report that both adrenergic and muscarinic receptor autoantibodies may be detected by ELISA in POTS patients. The most prevalent elevation of autoantibody in our investigation was antiadrenergic A1 receptor, and detection of other adrenergic and muscarinic receptor autoantibodies were not detected without elevation of autoantibodies against the A1 receptor. note: 'Found by winnow, kev and lev in p018, p024, p028. Claude judged: partial.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Several etiologies are suggested in patients with POTS; however, a considerable number of patients with POTS seem to have antibodies to one or more of the ARs according to recent studies.2, 3 Among the autoantibodies reported in POTS, approximately half of the patients had autoantibodies to β2AR in previous studies.2, 3 note: 'Found by winnow, kev and lev in p011, p016. Claude judged: partial.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: We found that anti‐gAChR antibodies were detected more frequently in patients with POTS compared to NMS and controls, suggesting that anti‐gAChR antibodies may be associated with POTS and its underlying autonomic dysfunction. POTS and NMS were clearly distinguishable by the prevalence of anti‐gAChR antibodies. note: 'Found by winnow, kev and lev in p012, p015, p017. Claude judged: partial.' - paper: pmid29618472 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Methods and Results quote: Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. note: 'Found by winnow, kev and lev in p023, p002, p003. Claude judged: partial.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: partial section: Results > Autoantibody activity quote: Based on these direct assays, 6 of these 17 POTS patients (35%) harboured both α1AR- and β1AR-AAb (Table 2). None of these autoantibodies were found in the patients with VVS or healthy controls. note: 'Found by winnow, kev and lev in p002, p018, p021. Claude judged: partial.' - paper: pmid24572257 cited: true text: full license: by-nc verdict: partial section: Abstract > Methods and Results quote: The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin. note: 'Found by winnow, kev and lev in p017, p022, p002. Claude judged: partial.' - paper: pmid23002038 cited: true text: full license: none verdict: partial section: 4 Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23002038. Found by winnow, kev and lev in p019, p021. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - differential_syncope_oh papers: 16 evidence: - paper: pmid33150760 cited: true text: full license: by verdict: supports section: Discussion quote: After performing tilt table testing on a group of suspected POTS patients in this study, ten were found to have orthostatic hypotension and nine had syncope. In patients with orthostatic symptoms, tilt table testing is the preferred tool for differentiating between these types of orthostatic intolerance. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid27525257 cited: true text: full license: by verdict: supports section: 1. Introduction quote: The tilt test was initially introduced to diagnose vasovagal syncope [2]. Since then the diagnostic utility of the tilt test has been expanded for diagnosis of orthostatic hypotension, autonomic failure, postural tachycardia syndrome, and other forms of orthostatic intolerance [3]. note: 'Found by winnow, kev and lev in p045, p001, p002. Claude judged: supports.' - paper: pmid35372154 cited: true text: full license: by verdict: partial section: Introduction quote: Currently, the differential diagnosis between these two diseases is mainly based on the clinical features and haemodynamic responses during the head-up tilt test (HUTT) (2, 7). note: 'Found by winnow, kev and lev in p003, p005, p021. Claude judged: partial.' - paper: pmid35097001 cited: true text: full license: by verdict: partial section: Abstract quote: 'Overall, 2,343 (48.1%) showed positive responses as follows: 1,260 (25.9%) with the mixed type, 34 (0.7%) with the cardioinhibitory type, 580 (11.9%) with the vasodepressor type, 179 (3.7%) with postural tachycardia syndrome (POTS), and 290 (6.0%) with orthostatic hypotension (OH).' note: 'Found by winnow, kev and lev in p015, p004, p018. Claude judged: partial.' - paper: pmid33886735 cited: true text: full license: by verdict: partial section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: A avaliação autonômica ampliada, com análise de vários parâmetros hemodinâmicos durante o teste de inclinação, é altamente recomendável na investigação e diagnóstico diferencial etiológico da SPOT. note: 'Found by winnow, kev and lev in p112. Claude judged: partial.' - paper: pmid33582941 cited: true text: full license: none verdict: partial section: Data and Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33582941. Found by winnow, kev and lev in p032, p013. Claude judged: partial.' - paper: pmid31250563 cited: true text: full license: by verdict: partial section: Abstract quote: Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in “false positives” in which tilt‐induced fainting (tilt+) occurs in the absence of real‐world fainting. note: 'Found by winnow, kev and lev in p001, p030, p025. Claude judged: partial.' - paper: pmid28720881 cited: true text: full license: by verdict: partial section: Results quote: Forty seven percent of the patients (219/464) showed changes in BP or HR during HUT that fulfilled criteria for OH or POTS. Twenty eight percent (132/464) of patients showed OH and 19% (87/464) POTS, and the others had normal results on HUT. note: 'Found by winnow, kev and lev in p010, p015. Claude judged: partial.' - paper: pmid28674628 cited: true text: full license: by-nc verdict: partial section: Results > Haemodynamic parameters quote: In agreement with the predefined diagnostic criteria, the small number of patients with OH showed significantly lower SBP and DBP during HUT, whereas those with POTS showed higher HR during HUT (table 2), both at 3 min of HUT and at the point of lowest BP. note: 'Found by winnow, kev and lev in p018, p002, p003. Claude judged: partial.' - paper: pmid28554964 cited: true text: full license: by verdict: partial section: Materials and Methods > Postural tachycardia syndrome quote: Excessive tachycardia preceding hypotension and bradycardia is often part of the vasovagal response, and can be observed during tilt table testing of patients diagnosed with VVS, who are free of chronic day‐to‐day symptoms of OI, but do have postural hypotension and therefore do not have POTS. note: 'Found by winnow, kev and lev in p001, p011. Claude judged: partial.' - paper: pmid28286774 cited: true text: full license: by verdict: partial section: 2. Materials and Methods > 2.3. Cardiovascular Reflex Tests > 2.3.5. HUT quote: OH was defined as a sustained diastolic BP drop of at least 10 mmHg or a systolic BP drop of at least 20 mmHg for normotensive subjects [22]. Vasovagal syncope was defined as a sudden BP and HR decline coupled with loss of consciousness. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: partial section: Methods > Diagnostic criteria of postural tachycardia syndrome and classic vasovagal syncope quote: Vasovagal syncope was defined as a reproduction of syncope during HUT associated with a characteristic pattern of pronounced hypotension, bradycardia, or asystole.4 note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid21977261 cited: true text: full license: none verdict: partial section: CONCLUSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p017, p019. Claude judged: partial.' - paper: pmid17205918 cited: true text: abstract license: none verdict: partial section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 17205918. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid16627440 cited: true text: abstract license: none verdict: partial section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16627440. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid11975909 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11975909. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - plasma_catecholamine_assay - evidence_for - hyperadrenergic_evidence papers: 14 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: In this study, patients with POTS after HSCT exhibited a significantly greater increase in NE levels upon standing, indicating heightened sympathetic activation. NE changes also correlated with changes in HR, supporting a central role for adrenergic signaling in post-HSCT POTS. note: 'Found by winnow, kev and lev in p032, p004, p023. Claude judged: supports.' - paper: pmid37261636 cited: true text: full license: by verdict: supports section: Results > Autonomic examination quote: Both the supine [PoTS 309.00 (175.00–405.75) ng/l, HC 173.00 (127.00–283.50) ng/l, p = 0.006] and upright [PoTS 648.50 (520.00–1053.00) ng/l, HC 408.00 (287.50–497.50) ng/l, p < 0.001] NE levels were higher in the PoTS group, with 53% of patients with PoTS having upright NE plasma levels higher than 600 ng/l, indicating a hyperadrenergic state (see Fig. 3B). note: 'Found by winnow, kev and lev in p019, p015. Claude judged: supports.' - paper: pmid34471549 cited: true text: full license: by verdict: supports section: 2. Case Presentation quote: Furthermore, her supine norepinephrine was 677 pg/mL and her standing norepinephrine level was 855 pg/mL, suggestive of hyperadrenergic POTS (Table 1). note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid33926653 cited: true text: full license: none verdict: supports section: DISCUSSION > Sodium Loading in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p036, p048. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: A dosagem de epinefrina e norepinefrina plasmática em posição supina e ortostática pode ser útil para identificar os casos hiperadrenérgicos, assim como a análise do sódio urinário nas 24 horas e os casos de depleção de volume.6 note: 'Found by winnow, kev and lev in p125. Claude judged: supports.' - paper: pmid33150760 cited: true text: full license: by verdict: supports section: Discussion quote: In the current study, NE levels in the supine and tilted position were available for 16 patients, with five (31.3%) patients having an upright level of NE above the threshold of 3.5 nmol/L, indicating an increased sympathetic drive. Between a third and a half of all patients with POTS belong to the hyperadrenergic type, characterized by high standing plasma NE levels, and this study supports these findings (2). note: 'Found by winnow, kev and lev in p025, p020. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: THE PATHOGENESIS OF POSTURAL TACHYCARDIA SYNDROME > The high catecholamine status quote: Jacob et al.[15] discovered that the plasma norepinephrine and epinephrine levels were significantly increased both in supine and in upright positions. Thieben et al.[9] also found a high adrenaline status (standing plasma norepinephrine level ≥2600 pg/ml) in POTS patients. note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Investigation of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Diagnosis > Diagnostic criteria for POTS (See also Figure 1) quote: Noradrenaline is measured after drawing a blood sample from the patient in both a supine and a standing position,[8] with the patient in each position for at least 15 min prior to blood sampling.[8] The increase in noradrenaline in the standing position indicates the patient belongs to this sub-group.[8] note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Clinical Presentation of Postural Tachycardia Syndrome (POTS) > Laboratory Abnormalities in POTS quote: We often measure plasma norepinephrine levels in both a supine and standing position (at least 15 minutes in each position prior to blood sampling). The supine norepinephrine is often high normal in patients with POTS, while the upright norepinephrine is usually elevated (>600 pg/ml), a reflection of the exaggerated neural sympathetic tone that is present in these patients while upright. note: 'Found by winnow, kev and lev in p016, p028. Claude judged: supports.' - paper: pmid41533304 cited: true text: full license: by verdict: partial section: Discussion quote: Heretofore, an upright plasma NE ≥ 600 pg/mL has been used as evidence of hyperadrenergic POTS. note: 'Found by winnow, kev and lev in p039, p010. Claude judged: partial.' - paper: pmid35992935 cited: true text: full license: by verdict: partial section: Discussion quote: In 67% of patients the norepinephrine concentrations during head-up tilt exceeded 3.55 nmol/l (equivalent to 600 pg/ml), which is an accepted diagnostic criterion for the presence of hyperadrenergic POTS (Schondorf and Low, 1993; Jacob and Biaggioni, 1999; Jacob et al., 2019). note: 'Found by winnow, kev and lev in p024, p017. Claude judged: partial.' - paper: pmid25120493 cited: true text: full license: by verdict: partial section: Sympathetic overactivity may be associated with POTS quote: Some investigations (Streeten et al., 1988; Schondorf and Low, 1993; Furlan et al., 1998; Jacob et al., 1999), but not all (Jacob et al., 2000; Lambert et al., 2008), have reported that POTS patients have greater systemic plasma noradrenaline concentrations at rest or during orthostasis compared with healthy controls, suggesting that POTS is associated with a hyperadrenergic state. note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid21266211 cited: true text: full license: none verdict: partial section: Results > Stand Test with Supine and Upright Vitals and Catecholamines quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21266211. Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - qsart_sudomotor_testing - evidence_for - neuropathic_evidence papers: 14 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Results > Focus on newly diagnosed POTS following COVID-19 infection and vaccination > Post-COVID POTS case vignette quote: QSART revealed a diffuse pattern of postganglionic, sympathetic-cholinergic sudomotor dysfunction, and the patient was therefore diagnosed with neuropathic POTS [42–44]. note: 'Found by winnow, kev and lev in p037. Claude judged: supports.' - paper: pmid40608783 cited: true text: full license: by verdict: supports section: 4. Discussion quote: This hypothesis has gained support from different assessment methods, including evidence of reduced IENFD on skin biopsies [7–10], findings of decreased norepinephrine spillover in the legs compared to the arms [3], supersensitivity of norepinephrine infusion in distal veins resembling the reaction in denervated veins [33], and impaired post-ganglionic sudomotor function upon measurement with QSART [9,12–14]. note: 'Found by winnow, kev and lev in p036, p005. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Introduction quote: This denervation will imply a mechanism of small fiber neuropathy (SFN). Evidence for this hypothesis includes findings of decreased norepinephrine spillover in the legs compared to the arms [5] and impaired sweat production on sudomotor testing [6-8]. note: 'Found by winnow, kev and lev in p005, p006, p035. Claude judged: supports.' - paper: pmid35181863 cited: true text: full license: none verdict: supports section: Case report quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35181863. Found by winnow, kev and lev in p004, p007. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid25120493 cited: true text: full license: by verdict: supports section: Sympathetic denervation may be associated with POTS quote: Examination of medical records of patients with POTS seen at the Mayo Clinic in Rochester indicated that half of the patients had evidence of peripheral sudomotor denervation as estimated by abnormal sudomotor axon reflex test and thermoregulatory sweat test (Thieben et al., 2007). note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid25033770 cited: true text: full license: none verdict: supports section: METHODS > Phenotypic classification quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25033770. Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p068, p075. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: supports section: Discussion quote: Consistent with the notion that neuropathic POTS represents a distal autonomic and small fiber neuropathy, our diagnostic criteria included distal small fiber pathology, impaired distal sensory function and impaired distal sudomotor function. We included impaired sudomotor function in this definition because this is the most distal autonomic function measure but excluded measures of heart rate variability because these are more proximal measures and seemed likely to be impaired only in more severe cases of POTS. note: 'Found by winnow, kev and lev in p016, p030. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: There have been several findings consistent with this hypothesis. The results of sudomotor axon reflex testing [22] and galvanic skin stimulation [23] support this as well as skin biopsy results [25]. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: partial section: Discussion quote: Sudomotor testing is also used, as a majority of POTS patients have neuropathic abnormalities. This test demonstrates the effectiveness of postganglionic sudomotor nerves. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Clinical evaluation of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p027. Claude judged: partial.' - paper: pmid21906029 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: A partial autonomic neuropathy has been proposed as playing a role in the pathophysiology of POTS [18]. We used QSART to assess the integrity of postganglionic cholinergic sudomotor fibres [15,28]. note: 'Found by winnow, kev and lev in p031. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - evidence_for - cerebral_hypoperfusion_evidence papers: 13 evidence: - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: supports section: CBF in OI > CBF in POTS quote: First, they showed that POTS participants had twice the drop in CBv on head‐up tilt compared with controls even though BP remained stable. note: 'Found by winnow, kev and lev in p029, p032, p036. Claude judged: supports.' - paper: pmid37227184 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37227184. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid35056406 cited: true text: full license: by verdict: supports section: Abstract quote: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background. note: 'Found by winnow, kev and lev in p015, p001, p013. Claude judged: supports.' - paper: pmid32545797 cited: true text: full license: by verdict: supports section: 4. Discussion quote: The three studies found that the blood flow velocity decrease in patients with a normal HUT but with OI symptoms was larger than in healthy volunteers and patients without OI, and similar to the patients with POTS or OH. These observations suggest that cerebral hypoperfusion is not only present in POTS and OH patients, but also in patients with OI symptoms without POTS and OH. note: 'Found by winnow, kev and lev in p018, p001, p020. Claude judged: supports.' - paper: pmid32140630 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: The main finding of this study is that extracranial Doppler imaging demonstrates a significant reduction in cerebral blood flow during head-up tilt test in ME/CFS patients compared to healthy controls. note: 'Found by winnow, kev and lev in p081, p073, p078. Claude judged: supports.' - paper: pmid30256820 cited: true text: full license: by verdict: supports section: Abstract quote: It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia. note: 'Found by winnow, kev and lev in p001, p020, p022. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p005, p022. Claude judged: supports.' - paper: pmid33947430 cited: true text: full license: by verdict: partial section: Introduction quote: We recently reported that extracranial Doppler imaging of the internal carotid and vertebral arteries can measure the total cerebral blood flow (CBF) during head-up tilt testing (HUT), and thereby provides an objective confirmation of OI. In healthy adults, this technique identified a mean 7% reduction in CBF during a 30 min HUT. note: 'Found by winnow, kev and lev in p008, p030. Claude judged: partial.' - paper: pmid33352894 cited: true text: full license: by verdict: partial section: 1. Introduction quote: According to a recent hypothesis, upright cognitive impairment in patients with POTS is caused by reduced cerebral blood flow velocity (CBFV), and studies have shown that CBFV decreases excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia [8]. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid33280488 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Methods and Results quote: Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). note: 'Found by winnow, kev and lev in p002, p012, p025. Claude judged: partial.' - paper: pmid33050553 cited: true text: full license: by verdict: partial section: Abstract quote: The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients. note: 'Found by winnow, kev and lev in p014, p001. Claude judged: partial.' - paper: pmid25002851 cited: true text: full license: by verdict: partial section: Introduction quote: Although on average CBF decreased more in POTS than controls (Ocon et al., 2009) more recent studies showed that large abnormal decreases in mean CBF occurred during orthostasis in a subset of POTS patients in whom a significantly decreased central blood volume during initial orthostasis triggered hyperpnea, hypocapnia, and sympathetic activation (Del Pozzi et al., 2014). note: 'Found by winnow, kev and lev in p003, p035. Claude judged: partial.' - paper: pmid16627440 cited: true text: abstract license: none verdict: partial section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16627440. Found by winnow, kev and lev in p002. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - evidence_for - pots papers: 12 evidence: - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: supports section: CBF in OI > CBF in POTS quote: CBv, measured in the middle cerebral artery (MCA), served as a more accurate tool in differentiating POTS from other forms of tachycardia. note: 'Found by winnow, kev and lev in p029, p036, p032. Claude judged: supports.' - paper: pmid27525257 cited: true text: full license: by verdict: supports section: 4. Discussion > 4.2. Tachycardia Syndromes (PST, IST, and POTS) quote: CBFv is also helpful in classification. CBFv is characteristically reduced in POTS, normal in IST, and normal or transiently elevated in PST. note: 'Found by winnow, kev and lev in p041, p045, p001. Claude judged: supports.' - paper: pmid39875497 cited: true text: full license: by verdict: partial section: Introduction quote: Previous transcranial Doppler studies have found reduced cerebral blood flow (CBF) in those with POTS during orthostatic and cognitive stress11–14. However, the Doppler technique remains confined to research settings due to the expertise and time required for measurements and potential inter-operator variability15. note: 'Found by winnow, kev and lev in p003, p009. Claude judged: partial.' - paper: pmid39297140 cited: true text: full license: by-nc-nd verdict: partial section: Results > Stroke volume and cerebrovascular pulsatility as determinants of postural ventilation and sympathetic activity in patients with POTS quote: Indeed, reductions in stroke volume were also predictive of reductions in MCAv pulsatility (Figure 3C), and we found that the reduction in MCAv pulsatility during head-up tilt was larger in patients with POTS compared with control subjects (Figure 3D, Table 3). note: 'Found by winnow, kev and lev in p031, p032. Claude judged: partial.' - paper: pmid37227184 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37227184. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35673757 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35673757. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid33352894 cited: true text: full license: by verdict: partial section: Abstract quote: The results of this study contribute toward developing an early accurate diagnosis of impaired CBFV responses to CO2 for POTS patients. note: 'Found by winnow, kev and lev in p001, p003, p008. Claude judged: partial.' - paper: pmid33280488 cited: true text: full license: by-nc-nd verdict: partial section: Discussion > Clinical Implications quote: Whether reduced CBFv is a useful biomarker in the management of POTS remains to be determined. note: 'Found by winnow, kev and lev in p002, p025, p033. Claude judged: partial.' - paper: pmid30256820 cited: true text: full license: by verdict: partial section: Abstract quote: During the tilt, CBFv decreased more in HYCH (-22.4±7.7%, p<0.0001) and POTS (-19.0±10.3%, p<0.0001) compared to controls (-3.0±5.0%). note: 'Found by winnow, kev and lev in p001, p022. Claude judged: partial.' - paper: pmid25510829 cited: true text: full license: none verdict: partial section: Results > Imposition of Graded Orthostatic Challenge > Autospectral Power- Oscillatory Data quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25510829. Found by winnow, kev and lev in p025, p019, p023. Claude judged: partial.' - paper: pmid25002851 cited: true text: full license: by verdict: partial section: Results > Upright > Autospectral power quote: Overall CBFv variability was markedly increased in POTS compared to supine or to upright control data (P < 0.001). While VLF cerebral blood flow velocity power did not differ for POTS compared to control subjects, LF power was significantly larger (P < 0.001) for POTS compared to controls when upright. note: 'Found by winnow, kev and lev in p018, p024, p001. Claude judged: partial.' - paper: pmid24711524 cited: true text: full license: none verdict: partial section: Results > Response to Orthostatic Stress > Neurocardiopulmonary Responses to Tilt quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p005, p023. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - hyperadrenergic_evidence papers: 11 evidence: - paper: pmid41300849 cited: true text: full license: by verdict: supports section: 4. Discussion quote: In the syncope with POTS group, hypertensive responses during HUTT were significantly more prevalent, observed in 45% of patients. This combined elevation of heart rate and blood pressure suggests a hyperadrenergic mechanism. note: 'Found by winnow, kev and lev in p050, p040. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Introduction quote: Hyperadrenergic POTS is characterized by high central sympathetic drive, evident by an increase in systolic blood pressure (SBP) on HUTT and a standing plasma norepinephrine level of 600 pg/mL or more1,2,9. note: 'Found by winnow, kev and lev in p004, p024. Claude judged: supports.' - paper: pmid33927679 cited: true text: full license: by verdict: supports section: Discussion quote: Autonomic testing in 4 of 6 patients in our series revealed findings potentially compatible with POTS, including 2 patients with both hypertension and tachycardia on HUT, consistent with a hyperadrenergic POTS subtype. note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid33886001 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33886001. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid32880754 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Investigations quote: The tilt table test demonstrated the presence of hyperadrenergic POTS (increase in heart rate >30 beats/min, rise in systolic blood pressure ≥10 mm Hg and serum norepinephrine level ≥600 pg/mL). note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p014, p019. Claude judged: supports.' - paper: pmid36000360 cited: true text: full license: by verdict: partial section: Results > POTS phenotypes quote: Hyperadrenergic POTS patients have increased levels of plasma norepinephrine during HUT [3]. note: 'Found by winnow, kev and lev in p015, p065. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid25033770 cited: true text: full license: none verdict: partial section: RESULTS > Autonomic Function Tests, BP monitoring, and Laboratory Data quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25033770. Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid21977261 cited: true text: full license: none verdict: partial section: CONCLUSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p001, p019, p007. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - pots papers: 10 evidence: - paper: pmid41300849 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Jacob et al. likewise demonstrated lower HF, rMSSD, and pNN50 values in POTS compared with non-POTS patients using short-term HRV [37]. note: 'Found by winnow, kev and lev in p031, p043, p044. Claude judged: partial.' - paper: pmid35118574 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35118574. Found by winnow, kev and lev in p027. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Fall 2 quote: Im Langzeit-EKG zeigten sich keine Herzrhythmusstörung, eine normale mittlere Herzfrequenz mit 80 Schlägen/min, aber eine relevante autonome Regulationsstörung mit herabgesetzter globaler HRV (SDNN = 95 ms, Normwert > 128). Basierend auf unseren Vorarbeiten über autonome Regulationsstörungen bei Kindern [2] und ersten Fallberichten aus der internistischen Kardiologie lag es nahe [6], dass diese postinfektiösen Probleme nach der SARS-CoV-2-Infektion Ausdruck eines sog. posturalen orthostatischen Tachykardiesyndroms (POTS) sind. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: The slope of ΔRR/ΔSAP is typically reduced in POTS21 compared with controls supine and even more when upright. note: 'Found by winnow, kev and lev in p008, p048. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Introduction quote: HRV parameters (HF and LF) during HUT test correlated with autonomic dysfunction in POTS and in other autonomic neuropathies (Baker et al., 2018b). HRV was lower for POTS patients than for controls in rest and during HUT tests (Stewart, 2000; Baker et al., 2018a; Jacob et al., 2019). note: 'Found by winnow, kev and lev in p004, p010, p027. Claude judged: partial.' - paper: pmid31780890 cited: true text: full license: by verdict: partial section: Results > Comparison of Baseline Demographic and HRV Parameters Between POTS and Control Groups quote: However, SDNN index, pNN50, TR index, LF, and TP were significantly higher in POTS than control children all P < 0.05. note: 'Found by winnow, kev and lev in p019, p032. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p001, p029, p033. Claude judged: partial.' - paper: pmid22247480 cited: true text: full license: none verdict: partial section: Results > Baroreflex Function quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22247480. Found by winnow, kev and lev in p025, p033. Claude judged: partial.' - paper: pmid21977261 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p001, p019. Claude judged: partial.' - paper: pmid10406593 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 10406593. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - cerebral_hypoperfusion_evidence papers: 9 evidence: - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Discussion > Pulmonary determinants quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid39544990 cited: true text: full license: by verdict: supports section: Discussion quote: In this study, orthostatic lightheadedness/dizziness was accompanied by reduced CBFv in both HYCH and POTS during the head-up tilt test. Our previous study (33) showed that changes in CBFv (in addition to end-tidal CO2 level that modulates the size of cerebral vessels) indeed correlate with symptoms of cerebral hypoperfusion indicating that reduced CBFv leads to cerebral hypoperfusion. note: 'Found by winnow, kev and lev in p016, p036. Claude judged: supports.' - paper: pmid35056406 cited: true text: full license: by verdict: supports section: Abstract quote: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background. note: 'Found by winnow, kev and lev in p013, p015, p001. Claude judged: supports.' - paper: pmid32140630 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: First, our study shows that in response to head-up tilt, ME/CFS patients with either delayed orthostatic hypotension or POTS develop a cerebral blood flow reduction of 28%, and 29%, respectively, at the end of the upright position. This is highly significantly different from the 7% reduction in controls with a normal tilt test. note: 'Found by winnow, kev and lev in p081, p072, p073. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Results > Response to Orthostatic Stress > Neurocardiopulmonary Responses to Tilt quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p001, p022, p023. Claude judged: supports.' - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: partial section: CBF in OI > CBF in POTS quote: First, they showed that POTS participants had twice the drop in CBv on head‐up tilt compared with controls even though BP remained stable. note: 'Found by winnow, kev and lev in p029, p036, p032. Claude judged: partial.' - paper: pmid33947430 cited: true text: full license: by verdict: partial section: Introduction quote: We recently reported that extracranial Doppler imaging of the internal carotid and vertebral arteries can measure the total cerebral blood flow (CBF) during head-up tilt testing (HUT), and thereby provides an objective confirmation of OI. In healthy adults, this technique identified a mean 7% reduction in CBF during a 30 min HUT. note: 'Found by winnow, kev and lev in p008, p030. Claude judged: partial.' - paper: pmid33352894 cited: true text: full license: by verdict: partial section: 1. Introduction quote: According to a recent hypothesis, upright cognitive impairment in patients with POTS is caused by reduced cerebral blood flow velocity (CBFV), and studies have shown that CBFV decreases excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia [8]. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid16627440 cited: true text: abstract license: none verdict: partial section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16627440. Found by winnow, kev and lev in p002. Claude judged: partial.' - edge: - muscle_sympathetic_nerve_activity - evidence_for - pots papers: 9 evidence: - paper: pmid41533304 cited: true text: full license: by verdict: partial section: Methods > Cut point search for DBP rise (DBPVM2l_rise) quote: We defined the optimal DBPVM2l_rise cut point as the value where the highest correlations between MSNA and DBPVM2l_rise were found in both hyperadrenergic (above the cut point value) and non-hyperadrenergic POTS (below the cut point value) using the golden section search method, as detailed in Appendix 1 [20]. note: 'Found by winnow, kev and lev in p003, p015, p022. Claude judged: partial.' - paper: pmid40951270 cited: true text: full license: by verdict: partial section: Methods > Cut point search for DBP rise (DBP) quote: Our primary objective was to find the optimal cut point value for DBPVM2l_rise to distinguish hyperadrenergic from non-hyperadrenergic POTS. We defined the optimal DBPVM2l_rise cut point as the cut point where the highest correlations between MSNA and DBPVM2l_rise were found in both hyperadrenergic (above cut point value) and non-hyperadrenergic POTS (below cut point value) using the golden section search method, as detailed in Appendix 1[24]. note: 'Found by winnow, kev and lev in p003, p026, p039. Claude judged: partial.' - paper: pmid40350041 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40350041. Found by winnow, kev and lev in p008, p011, p015. Claude judged: partial.' - paper: pmid39109428 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p003, p032, p006. Claude judged: partial.' - paper: pmid38176772 cited: true text: full license: none verdict: partial section: Discussion > Autonomic function quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38176772. Found by winnow, kev and lev in p004, p022. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p001, p026, p033. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid22934032 cited: true text: full license: by verdict: partial section: Pathophysiological conditions > Neural control in the postural orthostatic tachycardia syndrome quote: Microneurographic studies have shown that POTS patients have a similar (Bonyhay and Freeman, 2004; Muenter Swift et al., 2005; Lambert et al., 2008; Fu et al., 2010) or greater (Furlan et al., 1998) basal MSNA when compared to healthy controls. All (Muenter Swift et al., 2005; Lambert et al., 2008; Fu et al., 2010; Baumert et al., 2011) except one (Furlan et al., 1998) studies reported enhanced MSNA responses during orthostasis in POTS. note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - paper: pmid20035362 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - valsalva_maneuver - evidence_for - hyperadrenergic_evidence papers: 7 evidence: - paper: pmid41533304 cited: true text: full license: by verdict: supports section: Introduction quote: Indirect clinical markers of increased sympathetic activity, such as high systolic blood pressure (SBP) overshoot during Valsalva, orthostatic hypertension, high orthostatic plasma catecholamines [4–6], and response to sympatholytic drugs have been proposed [3, 7]. Recently, we showed that a subset of patients with POTS have increased resting MSNA, indicating greater central sympathetic outflow, and that can be identified by an exaggerated diastolic blood pressure (DBP) increase during late phase 2 of the Valsalva maneuver (DBPVM2l_rise). note: 'Found by winnow, kev and lev in p003, p006, p001. Claude judged: supports.' - paper: pmid40951270 cited: true text: full license: by verdict: supports section: Introduction quote: Indirect clinical markers of increased sympathetic activity like high systolic blood pressure (SBP) overshoot during Valsalva, orthostatic hypertension, high orthostatic plasma catecholamines[2–5], and response to sympatholytic drugs have been proposed[6, 7]. Recently, we showed that POTS patients with clinical hyperadrenergic features can be identified by an exaggerated diastolic blood pressure (DBP) increase during late phase 2 of the Valsalva maneuver (DBPVM2l_rise) and that this biomarker can also identify those who improved POTS symptoms with central sympatholytic therapy with guanfacine[8]. note: 'Found by winnow, kev and lev in p003, p038, p005. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p028, p038, p003. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p027, p001, p029. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: As manobras de Valsalva com medida da PA batimento por batimento podem mostrar uma fase 4 exagerada, revelando excessiva atividade simpática. note: 'Found by winnow, kev and lev in p125. Claude judged: supports.' - paper: pmid33886001 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33886001. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid32880754 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p008. Claude judged: supports.' - edge: - skin_biopsy_ienfd - evidence_for - neuropathic_evidence papers: 7 evidence: - paper: pmid42273028 cited: true text: full license: by verdict: supports section: Materials and methods > Participants quote: Of the initial pool of 382,256 (67%) underwent additional testing with either intraepidermal nerve fiber density skin biopsy (IENFD; through which reduced nerve fiber density evidence via punch biopsy is suggestive of small fiber neuropathy) or the quantitative sudomotor axon reflex test (QSART; low scores indicate abnormally low sweat response to electric stimulation of the skin and are considered suggestive of small autonomic nerve fiber damage) to identify presence or absence of the neuropathic subtype of POTS. note: 'Found by winnow, kev and lev in p006, p017. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Symptoms and clinicopathologic features of dysautonomia quote: Neuropathic POTS is associated with reduced intraepidermal and/or sudomotor (i.e., sweat gland) nerve fiber density on skin biopsy indicative of a small-fiber sensory or autonomic neuropathy. note: 'Found by winnow, kev and lev in p006, p014, p032. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Discussion quote: In this cohort, one of the largest POTS cohorts studied, we identified abnormal testing in 35% of patients who underwent at least one skin biopsy and/or QSART. These patients with evidence of autonomic SFN are likely to have a neuropathic subtype of POTS, though evidence of one subtype does not rule out the presence of other subtypes, given the heterogeneity of the disorder. note: 'Found by winnow, kev and lev in p005, p006, p033. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Case description and results quote: A skin biopsy from the distal lower leg 10mm above the malleolus lateralis confirmed a severe SFN with an intraepithelial nerve fiber density (IENFD) of 0,2/mm [28]. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid33764697 cited: true text: full license: by verdict: supports section: Introduction quote: Furthermore, in some patients with neuropathic POTS, intraepidermal nerve fiber density is decreased, providing objective support for a small fiber neuropathy in these POTS patients. note: 'Found by winnow, kev and lev in p007, p026, p027. Claude judged: supports.' - paper: pmid25053240 cited: true text: full license: none verdict: supports section: Clinical Summary quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25053240. Found by winnow, kev and lev in p014, p016, p017. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: supports section: Methods > Definition of neuropathic POTS quote: Neuropathic POTS was defined as a skin biopsy below the 5th percentile, and at least 1 other test (quantitative sensory testing or quantitative sudomotor direct and indirect testing) result below the 5th percentile. note: 'Found by winnow, kev and lev in p016, p030, p002. Claude judged: supports.' - edge: - muscle_sympathetic_nerve_activity - evidence_for - hyperadrenergic_evidence papers: 6 evidence: - paper: pmid41533304 cited: true text: full license: by verdict: supports section: Introduction quote: In a subset of these patients, the main pathophysiological mechanism has been proposed to be primary sympathetic activation (hyperadrenergic POTS) [2, 3]. Sympathetic activation can be measured directly using microneurography techniques to obtain muscle sympathetic nerve activity (MSNA). note: 'Found by winnow, kev and lev in p003, p006, p038. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p003, p032, p006. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid20035362 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid40951270 cited: true text: full license: by verdict: partial section: Discussion quote: The percentage is interestingly close to our previous study in which hyperadrenergic POTS was defined using the 4th quartile of baseline MSNA[8]. note: 'Found by winnow, kev and lev in p003, p040, p002. Claude judged: partial.' - paper: pmid15533861 cited: true text: abstract license: none verdict: partial section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15533861. Found by winnow, kev and lev in p002. Claude judged: partial.' - edge: - ambulatory_monitoring - evidence_for - pots papers: 6 evidence: - paper: pmid38176772 cited: true text: full license: none verdict: supports section: Results > Patient evaluation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38176772. Found by winnow, kev and lev in p023, p015. Claude judged: supports.' - paper: pmid35307584 cited: true text: full license: none verdict: supports section: Results > Study 2 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35307584. Found by winnow, kev and lev in p018, p011, p012. Claude judged: supports.' - paper: pmid39109119 cited: true text: full license: by verdict: partial section: Case presentation quote: The 72-hour Holter did demonstrate persistent sinus tachycardia and head-up tilt-table testing confirmed POTS (Table 1, Figure 1, Figure 2). note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid32846397 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32846397. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid32477718 cited: true text: full license: by verdict: partial section: Case presentation quote: 'However, during continuous monitoring via her loop recorder, within seconds of standing, sinus tachycardia (rate: 150 bpm) ensued without an appreciable drop in blood pressure (Figure 1).' note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid23270259 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23270259. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - valsalva_maneuver - evidence_for - pots papers: 6 evidence: - paper: pmid41533304 cited: true text: full license: by verdict: partial section: Conclusion quote: We propose a clinical marker from the Valsalva maneuver, namely DBPVM2l_rise, as a surrogate for sympathetic function that is applicable for POTS subtyping. The relationship of DBPVM2l_rise to sympathetic function has been confirmed by a strong correlation with B2B MSNA spike rateVM2 in healthy subjects. note: 'Found by winnow, kev and lev in p043, p003, p006. Claude judged: partial.' - paper: pmid40951270 cited: true text: full license: by verdict: partial section: Conclusion quote: We proposed a clinical marker from Valsalva maneuver, namely DBPVM2l_rise, as a surrogate for sympathetic function applicable for POTS subtyping. note: 'Found by winnow, kev and lev in p044, p003, p029. Claude judged: partial.' - paper: pmid33486983 cited: true text: full license: none verdict: partial section: RESULTS > Autonomic Testing quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33486983. Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p001, p034, p024. Claude judged: partial.' - paper: pmid25071706 cited: true text: full license: by verdict: partial section: Discussion quote: Autonomic testing showed a significantly higher Valsalva ratio in PoTS patients as compared to normal subjects. This conforms to former studies of Sandroni et al. who found a higher Valsalva ratio in PoTS patients and ascribed this to an increased β-adrenergic tone (22). note: 'Found by winnow, kev and lev in p014, p021. Claude judged: partial.' - paper: pmid23729158 cited: true text: full license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23729158. Found by winnow, kev and lev in p003, p020. Claude judged: partial.' - edge: - regional_norepinephrine_spillover - evidence_for - neuropathic_evidence papers: 5 evidence: - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Introduction quote: This denervation will imply a mechanism of small fiber neuropathy (SFN). Evidence for this hypothesis includes findings of decreased norepinephrine spillover in the legs compared to the arms [5] and impaired sweat production on sudomotor testing [6-8]. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid25053240 cited: true text: full license: none verdict: supports section: Clinical Summary quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25053240. Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: Using a segmental norepinephrine spillover approach, Jacob et al. [26] demonstrated that patients with POTS had normal sympathetic neuronal norepinephrine release in their arms, but less norepinephrine release (and thus less sympathetic activation) in their lower body. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid20035362 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - plasma_blood_volume_assay - evidence_for - pots papers: 5 evidence: - paper: pmid39614968 cited: true text: full license: by verdict: partial section: Abstract > Conclusions quote: The CO rebreathing method can detect BV deficit, as well as the RBCV deficit in patients with POTS. The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. note: 'Found by winnow, kev and lev in p004, p032, p035. Claude judged: partial.' - paper: pmid37393658 cited: true text: full license: none verdict: partial section: DISCUSSION > Blood Volume Abnormalities and Treatments in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p016, p020, p021. Claude judged: partial.' - paper: pmid33926653 cited: true text: full license: none verdict: partial section: RESULTS > Comparison of Low Salt Diet Response between POTS and Healthy Controls > Blood volume (Table 4; Figure 5) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p044, p038, p042. Claude judged: partial.' - paper: pmid23753844 cited: true text: full license: none verdict: partial section: Investigation of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p028, p020. Claude judged: partial.' - paper: pmid20579544 cited: true text: full license: none verdict: partial section: RESULTS > Physical characteristics quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p026, p035. Claude judged: partial.' - edge: - plasma_catecholamine_assay - evidence_for - pots papers: 5 evidence: - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Diagnosis > Diagnostic criteria for POTS (See also Figure 1) quote: A high plasma level of noradrenaline level is also considered useful to identify POTS patients, and is sometimes referred to as a hyper-adrenergic form of POTS. Noradrenaline is measured after drawing a blood sample from the patient in both a supine and a standing position,[8] with the patient in each position for at least 15 min prior to blood sampling.[8] note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid37261636 cited: true text: full license: by verdict: partial section: Results > Autonomic examination quote: Both the supine [PoTS 309.00 (175.00–405.75) ng/l, HC 173.00 (127.00–283.50) ng/l, p = 0.006] and upright [PoTS 648.50 (520.00–1053.00) ng/l, HC 408.00 (287.50–497.50) ng/l, p < 0.001] NE levels were higher in the PoTS group, with 53% of patients with PoTS having upright NE plasma levels higher than 600 ng/l, indicating a hyperadrenergic state (see Fig. 3B). note: 'Found by winnow, kev and lev in p015, p019. Claude judged: partial.' - paper: pmid34471549 cited: true text: full license: by verdict: partial section: 2. Case Presentation quote: Furthermore, her supine norepinephrine was 677 pg/mL and her standing norepinephrine level was 855 pg/mL, suggestive of hyperadrenergic POTS (Table 1). note: 'Found by winnow, kev and lev in p005, p009. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid21266211 cited: true text: full license: none verdict: partial section: Methods > Protocol quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21266211. Found by winnow, kev and lev in p021, p009. Claude judged: partial.' - edge: - skin_biopsy_ienfd - evidence_for - small_fiber_neuropathy_dx papers: 5 evidence: - paper: pmid42273028 cited: true text: full license: by verdict: supports section: Materials and methods > Participants quote: Of the initial pool of 382,256 (67%) underwent additional testing with either intraepidermal nerve fiber density skin biopsy (IENFD; through which reduced nerve fiber density evidence via punch biopsy is suggestive of small fiber neuropathy) or the quantitative sudomotor axon reflex test (QSART; low scores indicate abnormally low sweat response to electric stimulation of the skin and are considered suggestive of small autonomic nerve fiber damage) to identify presence or absence of the neuropathic subtype of POTS. note: 'Found by winnow, kev and lev in p006, p017. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Introduction quote: In clinical practice, patients with suspected neuropathic POTS may undergo a variety of testing for SFN, including skin biopsy and quantitative sudomotor axon reflex testing (QSART). In the previous series, 38-45% of patients biopsied had reduced IENFD [8,10], and 33-56% of patients had reduced sweat output [6,8]. note: 'Found by winnow, kev and lev in p006, p042. Claude judged: supports.' - paper: pmid36090156 cited: true text: full license: by-nc-nd verdict: supports section: Patient 2 quote: A lower leg punch biopsy showed marked reduction in the innervation of the epidermis by free nerve endings consistent with small fiber polyneuropathy. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Case description and results quote: A skin biopsy from the distal lower leg 10mm above the malleolus lateralis confirmed a severe SFN with an intraepithelial nerve fiber density (IENFD) of 0,2/mm [28]. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid33764697 cited: true text: full license: by verdict: supports section: Introduction quote: Furthermore, in some patients with neuropathic POTS, intraepidermal nerve fiber density is decreased, providing objective support for a small fiber neuropathy in these POTS patients. note: 'Found by winnow, kev and lev in p007, p003. Claude judged: supports.' - edge: - active_stand_test - evidence_for - hyperadrenergic_evidence papers: 4 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: In this study, patients with POTS after HSCT exhibited a significantly greater increase in NE levels upon standing, indicating heightened sympathetic activation. NE changes also correlated with changes in HR, supporting a central role for adrenergic signaling in post-HSCT POTS. note: 'Found by winnow, kev and lev in p004, p025, p032. Claude judged: partial.' - paper: pmid38937334 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p001, p025. Claude judged: partial.' - paper: pmid37508589 cited: true text: full license: by verdict: partial section: 2. The Development of POTS and Its Associated Manifestations quote: The criterion of hyperadrenergic POTS is defined by an elevation in norepinephrine of greater than 600 pg/mL upon standing and a systolic blood pressure increase of greater than 10 mmHg following 10 min of standing [20]. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid35733987 cited: true text: full license: by verdict: partial section: Results quote: Supine norepinephrine (Figure 2A) and epinephrine (Figure 2B) were similar between groups. In the standing position, both catecholamines significantly increased in POTS patients compared to the healthy controls (Figures 2C,D). note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - edge: - plasma_blood_volume_assay - evidence_for - hypovolemic_evidence papers: 4 evidence: - paper: pmid39614968 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: The CO rebreathing method can detect BV deficit, as well as the RBCV deficit in patients with POTS. The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. note: 'Found by winnow, kev and lev in p004, p032, p038. Claude judged: supports.' - paper: pmid33926653 cited: true text: full license: none verdict: supports section: DISCUSSION > Low Blood Volume in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p044, p009, p038. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Investigation of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p028, p020. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: partial section: DISCUSSION > POTS and “deconditioning” quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p026, p035. Claude judged: partial.' - edge: - active_stand_test - evidence_for - long_covid papers: 4 evidence: - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Pairwise comparison of the average increase in heart rate relative to basal values between the cohorts at each minute of the active standing test showed that in ME/CFS that developed after COVID-19, there is a more pronounced increase in heart rate starting from the 6th minute of the test compared to the control group. This allowed us to assume that POTS is one of the key characteristics of ME/CFS of post-COVID genesis. note: 'Found by winnow, kev and lev in p046. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Here we make the diagnosis of orthostatic intolerance and PASC using the NASA Lean Test for a patient who is also pregnant. note: 'Found by winnow, kev and lev in p002, p024. Claude judged: supports.' - paper: pmid36298551 cited: true text: full license: by verdict: supports section: Abstract quote: 'In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19).' note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid33935300 cited: true text: full license: by verdict: supports section: Diskussion quote: Am Fallbeispiel 2 können wir zeigen, dass Kinder nach SARS-CoV-Infektion eine chronische Regulationsstörung des autonomen Nervensystems mit einem POTS entwickeln können, welches in einem einfachen aktiven Stehtest mit kontinuierlicher EKG-Registrierung nachweisbar ist. note: 'Found by winnow, kev and lev in p007, p010. Claude judged: supports.' - edge: - head_up_tilt_test - evidence_for - long_covid papers: 4 evidence: - paper: pmid36614874 cited: true text: full license: by verdict: supports section: 3. Results > 3.3. Tilt Table Test Response quote: 'A total of 7/11 (63.64%) patients with PASC met criteria for POTS: they had more than a 30 bpm increase in heart rate that sustained for at least 30% of the entire tilt table duration.' note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid35381331 cited: true text: full license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p014, p004, p005. Claude judged: supports.' - paper: pmid42343084 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: The tilt table test, a diagnostic tool commonly used to evaluate orthostatic intolerance, provides a controlled setting to assess autonomic responses during postural changes15. Recent studies have demonstrated that long COVID-19 patients exhibit abnormal HR and BP responses during tilt testing, further supporting the role of ANS dysfunction in this condition16,17. note: 'Found by winnow, kev and lev in p004, p005, p039. Claude judged: partial.' - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: partial section: CBF in OI > CBF in Long COVID quote: "However, unlike the study by Novak et al,\n53\n in which a majority of participants with long COVID\ \ did not have orthostatic tachycardia, in the study by van Campen et al,\n54\n all participants with long\ \ COVID experienced orthostatic tachycardia on head‐up tilt." note: 'Found by winnow, kev and lev in p036, p035. Claude judged: partial.' - edge: - thermoregulatory_sweat_test - evidence_for - neuropathic_evidence papers: 4 evidence: - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Results > Representative cases > Postural tachycardia syndrome > Patient 15 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p022, p035. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid25033770 cited: true text: full license: none verdict: supports section: METHODS > Phenotypic classification quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25033770. Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome > Diagnostic Considerations quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p028. Claude judged: partial.' - edge: - valsalva_maneuver - evidence_for - neuropathic_evidence papers: 4 evidence: - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Discussion quote: This finding supports the view of neuropathic POTS as resulting from peripheral sympathetic denervation [15]. Given that a blunted phase II response was present in a small minority of patients tested, it is likely that this represents a specific but not sensitive marker for neuropathic POTS [6,8]. note: 'Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid30879357 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p033, p034, p006. Claude judged: supports.' - paper: pmid25033770 cited: true text: full license: none verdict: supports section: METHODS > Phenotypic classification quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25033770. Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid8988490 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 8988490. Found by winnow, kev and lev in p001. Claude judged: supports.' - edge: - cardiopulmonary_exercise_test - evidence_for - pots papers: 4 evidence: - paper: pmid41357159 cited: true text: full license: none verdict: partial section: Results > Heart rate quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p004, p012, p019. Claude judged: partial.' - paper: pmid40313612 cited: true text: full license: by verdict: partial section: Conclusion quote: These two exercise parameters—peak oxygen pulse and ETCO2—may serve as objective markers for POTS physiology and sympathetic hyperactivity, respectively. note: 'Found by winnow, kev and lev in p035, p004. Claude judged: partial.' - paper: pmid27884959 cited: true text: full license: by verdict: partial section: Discussion quote: 'Our results support a phenotypic distinction among adolescents with POTS based on circulation during exercise: one that maintains the normal coupling between Q˙ and V˙O2, another in whom Q˙ rises more than expected, and now a third in whom Q˙ rises less than expected, with respect to V˙O2. How Q˙ is matched to V˙O2, can provide insight into pathophysiology of each variant.' note: 'Found by winnow, kev and lev in p009, p010, p005. Claude judged: partial.' - paper: pmid25168872 cited: true text: full license: by verdict: partial section: Abstract quote: We previously showed that adolescents with postural orthostatic tachycardia syndrome (POTS) have excessive heart rate (HR) during, and slower HR recovery after, exercise – hallmarks of deconditioning. note: 'Found by winnow, kev and lev in p001, p004, p011. Claude judged: partial.' - edge: - urine_sodium_24h - evidence_for - hypovolemic_evidence papers: 3 evidence: - paper: pmid37508589 cited: true text: full license: by verdict: supports section: 2. The Development of POTS and Its Associated Manifestations quote: Patients with hypovolemic POTS typically exhibit reduced plasma volume, red blood cells (RBC), and urinary sodium excretion [22]. A study demonstrated that 28.9% of patients had a sodium excretion rate of less than 100 mEq/L within 24 h, which is indicative of low blood-volume status. note: 'Found by winnow, kev and lev in p005, p016. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Hypovolemic Pots: Salt Supplements, Oral Rehydration and Fludrocortisone' quote: A low concentration of urinary sodium is an indirect marker of hypovolemia (23, 27). Our previous work showed that, compared with the healthy control group, the concentration of 24-h urinary sodium was significantly lower in the POTS patients, and the symptom severity of children with POTS inversely correlated at a significant level with their 24-h urinary-sodium concentrations. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: THE PATHOGENESIS OF POSTURAL TACHYCARDIA SYNDROME > The low blood volume quote: Zhang et al.[14] found that low 24-h urinary sodium was related to the severity of the symptoms of POTS in children and adolescents. These findings also supported the hypothesis that low volume status might play a role in the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - edge: - autonomic_autoantibody_assay - evidence_for - long_covid papers: 3 evidence: - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 2. COVID-19-Related POTS > 2.2. Presumed Mechanism for COVID-19-Related POTS > 2.2.2. Hyperadrenergic Reaction quote: Autoantibodies to G-protein-coupled receptors were measured in a study of 31 patients with persistent long COVID-19 symptoms, and autoantibodies to β2-AR, α1-AR, angiotensin II AT1-receptor, nociceptin-like opioid receptor, and muscarinic M2-receptor were identified [33]. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 6. Diagnosis quote: The measurement of inflammation or autoimmunity markers is a reasonable option in the context of clinical suspicion of POTS associated with SARS-CoV-2 (41, 66). note: 'Found by winnow, kev and lev in p020. Claude judged: partial.' - paper: pmid36832445 cited: true text: full license: by verdict: partial section: 4. Discussion quote: We performed auto-antibody analysis in a research laboratory [17] and found different patterns of elevated auto-antibodies against G-protein-coupled receptors in children with long COVID and also after SARS-CoV-2 vaccination [18]. However, the auto-antibody concentrations against these receptors were not significantly different between the controls and the patients with POTS in a recent analysis [19]. note: 'Found by winnow, kev and lev in p027. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - long_covid papers: 3 evidence: - paper: pmid42343084 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: Their study demonstrated reduced HRV indices and blunted BRS during tilt-table testing, reinforcing the role of ANS dysregulation in the clinical presentation of long COVID. These findings underscore the need for objective physiological assessment in post-COVID populations and inform the rationale for our present investigation14. note: 'Found by winnow, kev and lev in p003, p004, p039. Claude judged: partial.' - paper: pmid36298551 cited: true text: full license: by verdict: partial section: Abstract quote: 'Conclusion: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.' note: 'Found by winnow, kev and lev in p001, p028, p029. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Fall 2 quote: Im Langzeit-EKG zeigten sich keine Herzrhythmusstörung, eine normale mittlere Herzfrequenz mit 80 Schlägen/min, aber eine relevante autonome Regulationsstörung mit herabgesetzter globaler HRV (SDNN = 95 ms, Normwert > 128). Basierend auf unseren Vorarbeiten über autonome Regulationsstörungen bei Kindern [2] und ersten Fallberichten aus der internistischen Kardiologie lag es nahe [6], dass diese postinfektiösen Probleme nach der SARS-CoV-2-Infektion Ausdruck eines sog. posturalen orthostatischen Tachykardiesyndroms (POTS) sind. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - qsart_sudomotor_testing - evidence_for - pots papers: 3 evidence: - paper: pmid35181863 cited: true text: full license: none verdict: supports section: Case report quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35181863. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid25180969 cited: true text: full license: by verdict: partial section: Discussion quote: Our QSART findings showing a relative increase in sweat volume in the lower limb support the concept that increased sympathetic activity may be a pathophysiological mechanism of POTS. note: 'Found by winnow, kev and lev in p022, p017. Claude judged: partial.' - paper: pmid20035362 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20035362. Found by winnow, kev and lev in p001, p004, p019. Claude judged: partial.' - edge: - urine_sodium_24h - evidence_for - pots papers: 3 evidence: - paper: pmid37705599 cited: true text: full license: by verdict: supports section: Discussion > VVS combined with POTS group quote: Zhang et al. reported that POTS children exhibited lower levels of 24 h U-Na than healthy children and the U-Na level was negatively correlated with clinical symptom severity. When 24 h U-Na was at 124 mmol, the sensitivity and specificity for identifying POTS children were 76.9% and 93%, respectively (9). note: 'Found by winnow, kev and lev in p024, p006, p022. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: partial section: 'Treatment of Hypovolemic Pots: Salt Supplements, Oral Rehydration and Fludrocortisone' quote: Our previous work showed that, compared with the healthy control group, the concentration of 24-h urinary sodium was significantly lower in the POTS patients, and the symptom severity of children with POTS inversely correlated at a significant level with their 24-h urinary-sodium concentrations. Twenty-four hours sodium concentrations of <124 mmol/24 h indicated the effectiveness of salt supplements for treating POTS patients (sensitivity 76.9%; specificity 93%) (27). note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: partial section: THE INDIVIDUALIZED TREATMENT OF POSTURAL TACHYCARDIA SYNDROME > The oral rehydration salts quote: The result showed that compared with the control group, the basal 24-h urinary sodium level was low in POTS group (117.09 ± 58.63 mmol/24 h vs. 193.88 ± 91.12 mmol/24 h, P = 0.004). Besides, the symptom severity was negatively correlated with basal 24-h urinary sodium excretion. note: 'Found by winnow, kev and lev in p009, p015. Claude judged: partial.' - edge: - cardiopulmonary_exercise_test - evidence_for - deconditioning_evidence papers: 2 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Exercise Physiology, Deconditioning, and POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p061, p075. Claude judged: supports.' - paper: pmid23729158 cited: true text: full license: none verdict: supports section: Schematic design of the study > Definition of different variables quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23729158. Found by winnow, kev and lev in p009, p026. Claude judged: supports.' - edge: - qsart_sudomotor_testing - evidence_for - hyperadrenergic_evidence papers: 2 evidence: - paper: pmid25180969 cited: true text: full license: by verdict: supports section: Discussion quote: Our QSART findings showing a relative increase in sweat volume in the lower limb support the concept that increased sympathetic activity may be a pathophysiological mechanism of POTS. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - qsart_sudomotor_testing - evidence_for - long_covid papers: 2 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: partial section: Results > Focus on newly diagnosed POTS following COVID-19 infection and vaccination > Post-COVID POTS case vignette quote: QSART revealed a diffuse pattern of postganglionic, sympathetic-cholinergic sudomotor dysfunction, and the patient was therefore diagnosed with neuropathic POTS [42–44]. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid36718227 cited: true text: full license: by-nc-nd verdict: partial section: Conclusion quote: A consistent abnormality was noted in sudomotor/sympathetic cholinergic function in patients with new-onset and worsening dysautonomia post-COVID-19 infection. note: 'Found by winnow, kev and lev in p030, p034. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - neuropathic_evidence papers: 2 evidence: - paper: pmid34674068 cited: true text: full license: by verdict: partial section: Discussion quote: In patients with neuropathic POTS, a continuous increase in the circumference of the lower leg was measured during the HUT position, most likely due to the increased pooling of blood as a consequence of the impaired vasoconstriction caused by the peripheral sympathetic dysfunction [2, 4, 31]. note: 'Found by winnow, kev and lev in p021, p003, p022. Claude judged: partial.' - paper: pmid8988490 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 8988490. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - neuropathic_evidence papers: 2 evidence: - paper: pmid30879357 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p001, p033, p035. Claude judged: supports.' - paper: pmid41767063 cited: true text: full license: by verdict: partial section: Discussion quote: 'The pathophysiology in this case supports a hypothesis of neuropathic POTS following HSCI. This is suggested by: (1) abnormal SSR and reduced HR variability (SDNN < 70 milliseconds) indicating sympathetic dysregulation [14], (2) absence of anemia/hypovolemia, (3) normal supine renin/aldosterone levels.' note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - edge: - active_stand_test - evidence_for - postinfectious_evidence papers: 2 evidence: - paper: pmid36611357 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Pairwise comparison of the average increase in heart rate relative to basal values between the cohorts at each minute of the active standing test showed that in ME/CFS that developed after COVID-19, there is a more pronounced increase in heart rate starting from the 6th minute of the test compared to the control group. This allowed us to assume that POTS is one of the key characteristics of ME/CFS of post-COVID genesis. note: 'Found by winnow, kev and lev in p046. Claude judged: partial.' - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Diskussion quote: Am Fallbeispiel 2 können wir zeigen, dass Kinder nach SARS-CoV-Infektion eine chronische Regulationsstörung des autonomen Nervensystems mit einem POTS entwickeln können, welches in einem einfachen aktiven Stehtest mit kontinuierlicher EKG-Registrierung nachweisbar ist. note: 'Found by winnow, kev and lev in p007, p010. Claude judged: partial.' - edge: - end_tidal_co2 - evidence_for - pots papers: 2 evidence: - paper: pmid35891154 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Our patient’s 34% reduction in end tidal CO2 is also consistent with POTS (see Figure 2). note: 'Found by winnow, kev and lev in p013, p008. Claude judged: supports.' - paper: pmid33352894 cited: true text: full license: by verdict: partial section: 3. Results quote: The POTS also showed a lower PETCO2 (24.67 ± 4.11 mmHg), MSBP, and MABP in comparison to the Healthy-Youth group at the tilt up position. note: 'Found by winnow, kev and lev in p030, p001, p075. Claude judged: partial.' - edge: - genetic_testing - evidence_for - pots papers: 2 evidence: - paper: pmid39964606 cited: true text: full license: by verdict: partial section: Conclusions and perspective quote: With convincing statistical significance, we have illuminated the role of both common and rare genetic variants in POTS development. note: 'Found by winnow, kev and lev in p008, p018, p047. Claude judged: partial.' - paper: pmid16203873 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16203873. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - qsart_sudomotor_testing - evidence_for - small_fiber_neuropathy_dx papers: 2 evidence: - paper: pmid42273028 cited: true text: full license: by verdict: supports section: Introduction quote: Testing necessary to characterize neuropathic POTS commonly includes methods to identify small-fiber neuropathy, such as nerve fiber density skin biopsy or quantitative sudomotor axon reflex testing (QSART) (7–9). note: 'Found by winnow, kev and lev in p006, p017. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Abstract quote: Skin biopsy and quantitative sudomotor axon reflex testing (QSORT) are preferred methods of assessment for autonomic small fiber neuropathy (SFN). note: 'Found by winnow, kev and lev in p006, p001, p033. Claude judged: supports.' - edge: - genetic_testing - evidence_for - autoimmune_evidence papers: 1 evidence: - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Autoimmune etiology is gaining increasing attention. The HLA association revealed in this study further emphasizes autoimmunity in the pathogenesis of POTS. note: 'Found by winnow, kev and lev in p001, p011, p018. Claude judged: supports.' - edge: - end_tidal_co2 - evidence_for - cerebral_hypoperfusion_evidence papers: 1 evidence: - paper: pmid30256820 cited: true text: full license: by verdict: partial section: Abstract quote: 'HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia.' note: 'Found by winnow, kev and lev in p001, p025. Claude judged: partial.' - edge: - cardiac_mri - evidence_for - deconditioning_evidence papers: 1 evidence: - paper: pmid20579544 cited: true text: full license: none verdict: partial section: DISCUSSION > POTS and “deconditioning” quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p035, p037. Claude judged: partial.' - edge: - plasma_blood_volume_assay - evidence_for - deconditioning_evidence papers: 1 evidence: - paper: pmid20579544 cited: true text: full license: none verdict: partial section: DISCUSSION > POTS and “deconditioning” quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p035. Claude judged: partial.' - edge: - ambulatory_monitoring - evidence_for - differential_syncope_oh papers: 1 evidence: - paper: pmid35372154 cited: true text: full license: by verdict: partial section: Abstract > Objectives quote: To explore the role of the Poincaré plot derived from a 24-hour Holter recording in distinguishing vasovagal syncope (VVS) from postural tachycardia syndrome (POTS) in pediatric patients. note: 'Found by winnow, kev and lev in p001, p007, p027. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - evidence_for - differential_syncope_oh papers: 1 evidence: - paper: pmid27525257 cited: true text: full license: by verdict: partial section: Abstract quote: 'Characteristic pattern associated with a particular orthostatic syndrome can be grouped into abnormalities predominantly affecting blood pressure (orthostatic hypotension, orthostatic hypertension syndrome, vasomotor oscillations, and neurally mediated syncope—cardioinhibitory, vasodepressor, and mixed), cerebral blood flow (orthostatic hypoperfusion syndrome, primary cerebral autoregulatory failure), and heart rate (tachycardia syndromes: postural tachycardia syndrome, paroxysmal sinus tachycardia, and inappropriate sinus tachycardia). Psychogenic pseudosyncope is associated with stable CBFv.' note: 'Found by winnow, kev and lev in p045, p001, p035. Claude judged: partial.' - edge: - ambulatory_monitoring - evidence_for - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid38937334 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - autonomic_autoantibody_assay - evidence_for - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: We also show that POTS following HSCT is associated with a significantly greater increase in NE levels upon standing and higher AR autoantibody activity—both of which correlate with changes in HR—supporting a central role for adrenergic signaling in post-HSCT POTS. note: 'Found by winnow, kev and lev in p025, p040, p004. Claude judged: partial.' - edge: - cardiopulmonary_exercise_test - evidence_for - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid40313612 cited: true text: full license: by verdict: partial section: Abstract > Conclusion quote: These exercise parameters may serve as markers for POTS physiology and sympathetic hyperactivity, both of which could play a role in the pathophysiology of SLS. note: 'Found by winnow, kev and lev in p004, p027. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid21977261 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p001, p019. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - hypermobility_heds papers: 1 evidence: - paper: pmid28286774 cited: true text: full license: by verdict: partial section: Abstract quote: Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research. note: 'Found by winnow, kev and lev in p001, p024, p027. Claude judged: partial.' - edge: - active_stand_test - evidence_for - hypovolemic_evidence papers: 1 evidence: - paper: pmid23538032 cited: true text: full license: none verdict: partial section: METHODS > Supine and Upright Posture Study quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23538032. Found by winnow, kev and lev in p013. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - evidence_for - long_covid papers: 1 evidence: - paper: pmid39895557 cited: true text: full license: by-nc-nd verdict: supports section: CBF in OI > CBF in Long COVID quote: In all these cases, monitoring CBF was the most sensitive and specific biomarker of disease. note: 'Found by winnow, kev and lev in p036, p035. Claude judged: supports.' - edge: - head_up_tilt_test - evidence_for - mast_cell_activation papers: 1 evidence: - paper: pmid39165715 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: In the present study, which did not reach statistical significance, serum tryptase levels (both baseline and after 45–60 min of the TILT-table test) were higher in patients presenting with symptoms related to MCA compared to others. note: 'Found by winnow, kev and lev in p022, p026. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - evidence_for - me_cfs papers: 1 evidence: - paper: pmid32140630 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: The main finding of this study is that extracranial Doppler imaging demonstrates a significant reduction in cerebral blood flow during head-up tilt test in ME/CFS patients compared to healthy controls. note: 'Found by winnow, kev and lev in p073, p078, p084. Claude judged: partial.' - edge: - autonomic_autoantibody_assay - evidence_for - neuropathic_evidence papers: 1 evidence: - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Discussion quote: In this case the diagnostic work-up of PoTS led to the diagnosis of autoimmune-mediated neuropathic PoTS as a crossroad of PoTS, SFN and autoimmunity. The characterisation of autoantibodies against adrenergic and muscarinic receptors is nowadays performed in specialized laboratories with the use of life-based bioassays on cardiomyocytes confirming the functional role of these autoantibodies [34]. note: 'Found by winnow, kev and lev in p014, p023. Claude judged: partial.' - edge: - muscle_sympathetic_nerve_activity - evidence_for - neuropathic_evidence papers: 1 evidence: - paper: pmid30879357 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30879357. Found by winnow, kev and lev in p001, p033, p034. Claude judged: partial.' - edge: - plasma_catecholamine_assay - evidence_for - neuropathic_evidence papers: 1 evidence: - paper: pmid35992935 cited: true text: full license: by verdict: partial section: Discussion quote: We therefore conclude that in patients with neuropathic POTS, the excessive increase in plasma norepinephrine in the upright position occurs mainly in response to the reduced vasoconstrictor function of the sympathetic nervous system. note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - quantitative_sensory_testing - evidence_for - neuropathic_evidence papers: 1 evidence: - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Discussion quote: Our definition thus has a structural small fiber criterion (intra-epidermal nerve fiber density), a functional small fiber criterion (quantitative sensory testing) and a functional autonomic criterion (quantitative sudomotor function testing). note: 'Found by winnow, kev and lev in p030, p022. Claude judged: partial.' - edge: - head_up_tilt_test - evidence_for - postinfectious_evidence papers: 1 evidence: - paper: pmid35381331 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p014, p008. Claude judged: partial.' - edge: - heart_rate_variability - evidence_for - postinfectious_evidence papers: 1 evidence: - paper: pmid33935300 cited: true text: full license: by verdict: partial section: Fall 2 quote: Im Langzeit-EKG zeigten sich keine Herzrhythmusstörung, eine normale mittlere Herzfrequenz mit 80 Schlägen/min, aber eine relevante autonome Regulationsstörung mit herabgesetzter globaler HRV (SDNN = 95 ms, Normwert > 128). Basierend auf unseren Vorarbeiten über autonome Regulationsstörungen bei Kindern [2] und ersten Fallberichten aus der internistischen Kardiologie lag es nahe [6], dass diese postinfektiösen Probleme nach der SARS-CoV-2-Infektion Ausdruck eines sog. posturalen orthostatischen Tachykardiesyndroms (POTS) sind. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - cardiac_mri - evidence_for - pots papers: 1 evidence: - paper: pmid20579544 cited: true text: full license: none verdict: supports section: DISCUSSION > “The Grinch syndrome” – a new name for POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p026, p035, p037. Claude judged: supports.' - edge: - regional_norepinephrine_spillover - evidence_for - pots papers: 1 evidence: - paper: pmid25120493 cited: true text: full license: by verdict: partial section: Sympathetic overactivity may be associated with POTS quote: More robust and precise assessment of sympathetic activity by direct measurements of total body and regional noradrenaline spillover have been performed in a few investigations and the results have been variable. Evidence of sympathoexitation was confirmed in one study (Jordan et al., 2002), but not in others (Jacob et al., 1999; Goldstein et al., 2002a; Lambert et al., 2008). note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - edge: - skin_biopsy_ienfd - evidence_for - pots papers: 1 evidence: - paper: pmid25053240 cited: true text: full license: none verdict: partial section: Clinical Summary quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25053240. Found by winnow, kev and lev in p014, p016. Claude judged: partial.' - edge: - quantitative_sensory_testing - evidence_for - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid33299671 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33299671. Found by winnow, kev and lev in p004. Claude judged: supports.' - edge: - thermoregulatory_sweat_test - evidence_for - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid33860871 cited: true text: full license: none verdict: supports section: Results > Representative cases > Postural tachycardia syndrome > Patient 15 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p022. Claude judged: supports.' - edge: - beta_blocker_therapy - indicates - hyperadrenergic_evidence papers: 28 evidence: - paper: pmid41767063 cited: true text: full license: by verdict: supports section: Treatment and Outcomes quote: Metoprolol was considered a rational choice as the patient's clinical presentation was dominated by sympathetic hyperactivity and marked tachycardia with relatively stable blood pressure. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid40626134 cited: true text: full license: by verdict: supports section: THE CURRENT STATUS OF INDIVIDUALIZED TREATMENT OF POTS IN CHILDREN > β‐Adrenergic receptor blockers in treating children with POTS quote: β‐Adrenergic receptor blockers can block the effect of excessively increased catecholamine levels in some patients to alleviate symptoms. Biomarkers or indices reflecting hyperadrenergic status could guide the therapeutic response to β‐adrenoreceptor blockers, such as metoprolol. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Given our findings suggesting a central role for adrenergic signaling in the development of POTS post-HSCT, treatment with a nonselective β-AR blocker such as propranolol may be appropriate. note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid39768649 cited: true text: full license: by verdict: supports section: 4. Discussion quote: In case of a hyperadrenergic reaction, beta-blockade or ivabradine may be preferable, whether in combination with blood volume increasing interventions or not. note: 'Found by winnow, kev and lev in p038, p035. Claude judged: supports.' - paper: pmid39706392 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39706392. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.5. Treatments for COVID-19-Related POTS Due to Increased Norepinephrine in the Blood quote: β-blockers can inhibit β-ARs that react to norepinephrine or epinephrine secreted from sympathetic nerve endings. The β-blockers help reduce tachycardia, decrease excess epinephrine, and alleviate orthostatic intolerance [52]. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p003, p029. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Discussion quote: For example, for hyperadrenergic POTS, the sympathetic output is blocked via beta-blockers, or sympathetic symptoms such as tachycardia may be combated by pharmacotherapies such ivabradine which inhibits I(f) channels. note: 'Found by winnow, kev and lev in p021, p005. Claude judged: supports.' - paper: pmid38033543 cited: true text: full license: by verdict: supports section: Introduction quote: Metoprolol acts as a blocker by antagonizing adrenergic receptor hyperactivation and has been speculated to work mainly in children with a hyperadrenergic state. Therefore, biomarkers are needed to identify children with a high adrenergic status in clinical practice to individualize the therapeutic regimen and improve the efficacy of pediatric POTS management. note: 'Found by winnow, kev and lev in p005, p027, p025. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: '4. Individualized Pharmacologic Therapies for Pediatric POTS: Predictors of Therapeutic Efficacy > 4.3. Predictors for Metoprolol Efficacy in Pediatric POTS' quote: For the POTS patients with an overactivated sympathetic activity as the primary pathophysiologic mechanism, metoprolol reduces heart-rate stimulation, counters the effects of elevated catecholamine levels, and alleviates symptoms by targeting β-adrenergic receptors. note: 'Found by winnow, kev and lev in p031, p032. Claude judged: supports.' - paper: pmid36781629 cited: true text: full license: by verdict: supports section: Introduction quote: Since metoprolol blocks β-adrenoceptors within cardiovascular tissues to reduce excessive sympathetic nerve activity in POTS, it would be only effective for POTS patients with high plasma catecholamine levels and sympathetic activity as the main pathogenesis [6]. note: 'Found by winnow, kev and lev in p006, p034, p035. Claude judged: supports.' - paper: pmid36187012 cited: true text: full license: by verdict: supports section: Introduction quote: Metoprolol, one of the most prescribed β-adrenoceptor blockers, targets the adrenergic receptor to lessen the symptoms of pediatric patients with POTS with increased sympathetic activity as the main pathogenic mechanism. note: 'Found by winnow, kev and lev in p022, p023, p006. Claude judged: supports.' - paper: pmid36158335 cited: true text: full license: by verdict: supports section: Discussion quote: In this patient, the effectiveness of metoprolol in resolving her symptoms suggests sympathetic dysregulation as an underlying etiology of her symptoms. note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.4. Physiological Predictors for the Efficacy of Metoprolol in Pediatric POTS quote: Beta-adrenoceptor blockers are often applied in the management of pediatric POTS patients. They inhibit sympathetic nervous system activity and reduce stimulation of the heart rate and cardiac baroreceptors, thereby blocking the effects of increased blood catecholamine levels. note: 'Found by winnow, kev and lev in p010, p038, p040. Claude judged: supports.' - paper: pmid35127870 cited: true text: full license: by verdict: supports section: Discussion quote: Metoprolol, as a β-adrenergic receptor blocker, is only effective for POTS children with overexcitement of sympathetic nerve function or high catecholamine status by acting on β1 receptor (30). The patients of POTS with other mechanisms as mentioned above might be the non-responders to the treatment of metoprolol. note: 'Found by winnow, kev and lev in p005, p035, p032. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Introduction quote: If the burst of sympathetic activity is excessive, there will be a hyperadrenergic response with orthostatic tachycardia. This is the rationale for the use of low-dose beta-blockers in POTS. note: 'Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Management Strategies for Pots in Children and Adolescents > Pharmacological Treatment quote: β1-Selective blockers are useful for “hyperadrenergic” subtypes of POTS patients (96). note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Hyperadrenergic Pots: β-Blockers' quote: In the treatment of this type of POTS, β-blockers for blocking β-adrenoceptors are preferred, which could prevent the effect of having excessive catecholamines in the plasma. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Treatment quote: In the less common presentation of POTS with “hyperadrenergic response” in the upright position, improper baroreceptor function results in sustained high sympathetic tone that may be due to increased production or decreased clearance of norepinephrine. As such, alpha-agonist therapy (eg, midodrine) may be less desirable and, instead, nonselective β-blocker (propranolol23) or ivabradine24 (approved by the United States Food and Drug Administration for chronic heart failure treatment only) may be helpful. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid31412221 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31412221. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid25811760 cited: true text: full license: by verdict: supports section: Discussion quote: It is used to treat POTS by blocking β-adrenoceptor, and as a result, blocking high levels of catecholamines in circulation, and lowering the heart rate [3]. note: 'Found by winnow, kev and lev in p002, p018, p003. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: 'Treatment approaches: Addressing neurohormonal imbalances (Table 1) > Hyperadrenergic state—heart rate control' quote: Attempts to manage the hyperadrenergic state in these individuals center around HR control. The use of beta-blockade to decrease HR has been met with conflicting data. note: 'Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Beta-blockers quote: Beta blockers have been reported to be a useful treatment for POTS patients with beta-receptor super-sensitivity, high noradrenaline levels and/or hyper-adrenergic states. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: supports section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038, p035. Claude judged: supports.' - paper: pmid42132710 cited: true text: full license: by verdict: partial section: Discussion > Prior studies and beneficial usage of ivabradine and beta-blockers in POTS quote: Beta-blockers, specifically propranolol, have been shown, in low doses, to improve orthostatic tachycardia and reduce norepinephrine levels in these patients.6 note: 'Found by winnow, kev and lev in p052. Claude judged: partial.' - paper: pmid34035985 cited: true text: full license: by verdict: partial section: Discussion quote: Hyperadrenergic forms of POTS may respond to agents such as labetalol and clonidine due to their sympatholytic activity.8 Low-dose propranolol has also demonstrated efficacy in reducing tachycardia and achieving symptomatic control in POTS.9 note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Treatment of POTS (Table 2) > Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p039. Claude judged: partial.' - paper: pmid25204388 cited: true text: full license: by verdict: partial section: Background quote: Differences in noradrenergic activity between hyperadrenergic and other types of POTS may explain this inconsistency, and previous studies of efficacy of β-blockers in POTS subjects did not stratify participants into POTS subtypes according to their underlying causes. Hyperadrenergic subgroup with β-blockers would seem reasonable. note: 'Found by winnow, kev and lev in p003, p017, p005. Claude judged: partial.' - edge: - volume_expansion_therapy - indicates - hypovolemic_evidence papers: 23 evidence: - paper: pmid42037960 cited: true text: full license: by verdict: supports section: Discussion quote: When hypovolemia is suspected, fludrocortisone, a synthetic mineralocorticoid, is commonly used to expand plasma volume and promote sodium retention, though potential side effects include acne, headache, hypokalemia, and fluid retention. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 4 Discussion > 4.5 Rationality of current treatment approaches quote: Clinicians are advised to consider increasing salt intake or using water retention agents as a treatment strategy to improve hypovolemia and thereby alleviate POTS symptoms [12]. note: 'Found by winnow, kev and lev in p060. Claude judged: supports.' - paper: pmid38328599 cited: true text: full license: by verdict: supports section: Summary figure quote: Patients with hypovolemic POTS may increase circulating blood volume through exercise, hydration, salt loading, and compression stockings. These patients are often prescribed fludrocortisone and desmopressin in an effort to retain water and salt and to limit potential fluctuations in circulating blood volume. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Introduction quote: For hypovolemic POTS, interventions are aimed at increasing plasma volume, including but not limited to high fluid and salt intake, exercise, and fludrocortisone3. note: 'Found by winnow, kev and lev in p021, p005. Claude judged: supports.' - paper: pmid37393658 cited: true text: full license: none verdict: supports section: DISCUSSION > Blood Volume Abnormalities and Treatments in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Case summary > Management quote: Fludrocortisone is recommended for those with hypovolemia to increase sodium retention and expand the volume, but this effect might only last a few days.1 note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Pharmacologic management > Fludrocortisone and desmopressin quote: For hypovolemic POTS, fludrocortisone and desmopressin may help with symptom control. Fludrocortisone is a mineralocorticoid with glucocorticoid activity that works by increasing salt and water retention, which subsequently increases the intravascular volume, preventing compensatory tachycardia.17 note: 'Found by winnow, kev and lev in p013, p015. Claude judged: supports.' - paper: pmid33926653 cited: true text: full license: none verdict: supports section: DISCUSSION > Sodium Loading in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p046, p001, p010. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Management Strategies for Pots in Children and Adolescents > Pharmacological Treatment quote: Pediatric patients with POTS who are strongly suspected of having hypovolemia or inadequate salt intake are recommended to use oral rehydration salts (ORSs) for 1–3 months (5, 23, 98, 104) or to accept short-term intravenous saline as rescue treatment for patients with clinical decompensation and significant deterioration of symptoms (25). Saline supplements can alleviate symptoms in “hypovolemic” patients. note: 'Found by winnow, kev and lev in p024, p008, p023. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p022, p023. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Volume Expansion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p015, p019. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Sodium chloride 0.9% (Normal saline) quote: This appears to be a good, low-cost treatment option with few side effects for POTS patients who suffer hypovolemia caused by sympathetic neuropathy, which leads to venous pooling during upright posture, or other idiopathic causes.[28] note: 'Found by winnow, kev and lev in p018, p020. Claude judged: supports.' - paper: pmid22561596 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22561596. Found by winnow, kev and lev in p001, p007, p029. Claude judged: supports.' - paper: pmid20668563 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Tachycardia associated with POTS has been shown to respond acutely to the bolus administration of isotonic fluids to correct the underlying hypovolemia.[18] note: 'Found by winnow, kev and lev in p013, p009. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pharmacological Treatment of POTS quote: In patients in whom the presence of hypovolemia is either known or strongly suspected, fludrocortisone (an aldosterone analogue) is often used. Through enhanced sodium retention, it should expand the plasma volume, although there is a paucity of data regarding the exact mechanisms of action. note: 'Found by winnow, kev and lev in p039. Claude judged: supports.' - paper: pmid9244228 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 9244228. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: partial section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.2. Physiological Predictors for the Oral Rehydration Salts Efficacy in Pediatric POTS quote: Hypovolemia is one of the pathogeneses of POTS. Although the underlying pathophysiology of POTS is uncertain and much effort has been made to treat cases, increasing the blood volume by elevating salt and fluid consumption has been confirmed to benefit children and adolescents with POTS. note: 'Found by winnow, kev and lev in p016, p018. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Treatment > Nonpharmacologic interventions quote: Patients with hypovolemia should increase their daily fluid and salt intake to increase the fluid volume within the intravascular space and assist in preventing dehydration. note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid33689063 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33689063. Found by winnow, kev and lev in p001, p007. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Discussion quote: Fluid intake up to 2.5 liters daily, which is equivalent to 10 standard cups a day and a total of 10 grams of sodium chloride daily, noting that one salt tablet contains one gram of sodium chloride, helps expand the plasma volume and improve venous return and the re-loading of the right atrium. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid32494413 cited: true text: full license: by verdict: partial section: Ms. Lei, Ms. Sheikh, and Dr. Raj consider quote: Lasting improvements in POTS symptoms rely on therapy regimens founded upon lifestyle changes that begin with the maintenance of high fluid and dietary salt intake, with the primary goal of augmenting plasma volume. A high-sodium diet has been shown to expand both total blood volume and plasma volume, concurrently reducing orthostatic tachycardia and upright plasma norepinephrine.10 note: 'Found by winnow, kev and lev in p035, p010. Claude judged: partial.' - paper: pmid30001836 cited: true text: full license: none verdict: partial section: 3. VOLUME EXPANSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p014, p001. Claude judged: partial.' - paper: pmid28185102 cited: true text: abstract license: none verdict: partial section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28185102. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - immunomodulatory_therapy - indicates - autoimmune_evidence papers: 13 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Abstract quote: The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. note: 'Found by winnow, kev and lev in p001, p022, p025. Claude judged: supports.' - paper: pmid38311655 cited: true text: abstract license: none verdict: supports section: Abstract > Objective quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38311655. Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid35557616 cited: true text: full license: by verdict: supports section: Case Presentation quote: In view of his multiple autoimmune diseases (PANS, thyroiditis, celiac disease) and markers of active autoimmunity (lymphopenia, thrombocytopenia, anti-platelet antibodies, anti-histone antibodies, anti-thyroid antibodies, and complement consumption/activation), we initiated immunomodulation with rituximab, nine weekly intravenous methylprednisolone infusions, methotrexate, and hydroxychloroquine. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: These findings suggest that autoimmune-mediated neuropathic PoTS can be treated sufficiently with IVIg whereas SCIg minimizes side-effects. note: 'Found by winnow, kev and lev in p010, p004, p005. Claude judged: supports.' - paper: pmid34117922 cited: true text: full license: by verdict: supports section: Immunomodulatory treatment in postural tachycardia syndrome quote: However, there is increasing interest in the potential for immunotherapy in POTS, as a result of the accumulation of evidence for autoimmunity as a causal factor in a subset of patients. The aim of this case-series was to evaluate the use of intravenous immunoglobulin therapy (IVIG) in six patients with refractory POTS disease with serological evidence for autoimmunity. note: 'Found by winnow, kev and lev in p014, p015, p002. Claude judged: supports.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: supports section: Discussion > Immunomodulatory Treatments in Patients With POTS quote: The present results support the hypothesis that POTS is an autoimmune disease, which, in turn, may suggest that some patients with POTS could benefit from immunomodulatory therapies. note: 'Found by winnow, kev and lev in p037, p036. Claude judged: supports.' - paper: pmid29781817 cited: true text: abstract license: none verdict: supports section: Abstract > Study Design quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29781817. Found by winnow, kev and lev in p003, p006. Claude judged: supports.' - paper: pmid40624434 cited: true text: full license: by verdict: partial section: Treatment quote: Finally, immunotherapy is emerging as potentially effective in severe, treatment-refractory patients with POTS, post-COVID dysautonomia and other forms of dysautonomia and is considered standard therapy for autonomic disorders such as autoimmune autonomic ganglionopathy (AAG) and autoimmune autonomic neuropathies (AAN) in general [36–38]. note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.6. Treatment quote: The question arose whether the available knowledge pertaining to the autoimmunity in orthostatic intolerance patients would predict a role for immune modulation therapeutics in patients with refractory orthostatic intolerance and evidence of existing AAbs. Several case reports and case series demonstrate that immune modulation agents have a possible role in the treatment of orthostatic intolerance in patients who have symptoms refractory to the commonly used pharmacological and non-pharmacological treatments. note: 'Found by winnow, kev and lev in p033, p038. Claude judged: partial.' - paper: pmid36008726 cited: true text: abstract license: none verdict: partial section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36008726. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Because the autoimmune nature of POTS is suspected to be related to adrenergic autoantibodies, it is possible that upstream inhibition of TNF-alpha alters the levels and activity of these antibodies, attenuating the inflammatory response that induces symptoms. Although the exact mechanism behind the treatment’s efficaciousness must be further studied, we present one of the first recorded alleviations of POTS using immunomodulatory therapy. note: 'Found by winnow, kev and lev in p007, p009. Claude judged: partial.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: While lacking in vivo animal model confirmation, the strong association found in the HLA‐DQ locus, along with the functionality of the autoantibodies demonstrated experimentally,2, 3 supports the hypothesis that autoimmune POTS is antibody‐mediated. Immunotherapeutic agents, including IVIg, may be considered for the treatment of prominent POTS in this regard. note: 'Found by winnow, kev and lev in p015, p014. Claude judged: partial.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: partial section: Conclusion quote: This concept, if validated, would provide concrete support for novel therapeutic approaches against POTS based on immunotherapy. These could currently include suppression of autoantibody production using immunoglobulin infusions and in the foreseeable future by development of decoy peptides that are specific for autoantibodies that target the identified receptor epitopes. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - edge: - exercise_reconditioning - indicates - deconditioning_evidence papers: 11 evidence: - paper: pmid39597891 cited: true text: full license: by verdict: supports section: '2. POTS and Exercise: What Is Known' quote: Both programs follow a traditional graded cardiovascular exercise approach with the assumption that cardiovascular deconditioning is involved in POTS [21]. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p001, p003, p005. Claude judged: supports.' - paper: pmid25487551 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25487551. Found by winnow, kev and lev in p003, p008. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: Recovery > Management of POTS and Associated Conditions > “Get Moving”—Exercise and Activity in the Management of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p097. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p033, p041. Claude judged: supports.' - paper: pmid39678714 cited: true text: full license: by-nc verdict: partial section: Results quote: According to the study, it was found that POTS may be a result of deconditioning, and that a carefully prescribed exercise training program can be an effective non-drug therapy option for patients with POTS. note: 'Found by winnow, kev and lev in p034, p041. Claude judged: partial.' - paper: pmid37598401 cited: true text: full license: by verdict: partial section: Discussion quote: In line with previous work, the individuals with POTS recruited in this study were primarily deconditioned and over half were severely deconditioned. Although symptoms for individuals with POTS are caused by a variety of factors, results of this study highlight that an exercise intervention can improve deconditioning with an observed increase in peak VO2 of 3.4 mL/min/kg on average, which was almost 12% predicted and meant a shift from being severely deconditioned to moderately deconditioned for the ET group. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Many of our patients with POTS are bed rested and cardiovascular deconditioned. Our findings are, therefore, highly consistent with studies53,54 indicating that exercise reconditioning may be the ideal treatment for POTS because it increases parasympathetic and decreases sympathetic cardiac activity. note: 'Found by winnow, kev and lev in p057. Claude judged: partial.' - paper: pmid28286774 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Accordingly, it seems reasonable that exercise-based rehabilitation may be effective in the medium- and long-term treatment of POTS and related conditions with deconditioning [30]. note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid21690484 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21690484. Found by winnow, kev and lev in p032, p024. Claude judged: partial.' - paper: pmid19207771 cited: true text: full license: none verdict: partial section: Management > Deconditioned POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p030. Claude judged: partial.' - edge: - central_sympatholytic_therapy - indicates - hyperadrenergic_evidence papers: 10 evidence: - paper: pmid42696970 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42696970. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid41533304 cited: true text: full license: by verdict: supports section: Discussion quote: Furthermore, patients identified using the DBPVM2l_rise clinical biomarker reported clinical improvements after treatment with the central sympatholytic guanfacine, consistent with the hypothesis that this is a central hyperadrenergic POTS phenotype. note: 'Found by winnow, kev and lev in p035, p041. Claude judged: supports.' - paper: pmid40951270 cited: true text: full license: by verdict: supports section: Discussion quote: Hyperadrenergic POTS is one of the major subtypes that could benefit from sympatholytics, if correctly identified. note: 'Found by winnow, kev and lev in p042, p005. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p004, p005, p028. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Pharmacologic Treatment > Postural Orthostatic Tachycardia Syndrome49,50,170' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p166. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p039, p015. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Vanderbilt Approach to Pharmacotherapy for POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pharmacological Treatment of POTS quote: Central sympatholytic medications are often useful and well tolerated in patients with the central hyperadrenergic form of POTS, but may not be as well tolerated in neuropathic POTS. note: 'Found by winnow, kev and lev in p029, p034, p040. Claude judged: supports.' - edge: - lifestyle_modification - indicates - hypovolemic_evidence papers: 6 evidence: - paper: pmid41301791 cited: true text: full license: by verdict: partial section: 4. Neurologic Evaluation > 4.5. Treatment quote: Elevating the head of the bed to 70 degrees may decrease nocturia and help with morning dizziness and presyncope by reducing the release of atrial natriuretic peptide, thereby reducing hypovolemia. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid37393658 cited: true text: full license: none verdict: partial section: DISCUSSION > Blood Volume Abnormalities and Treatments in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37393658. Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid33689063 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33689063. Found by winnow, kev and lev in p007, p001. Claude judged: partial.' - paper: pmid32974246 cited: true text: full license: by verdict: partial section: Management Strategies for Pots in Children and Adolescents > Non-pharmacological Interventions quote: Low-flow POTS patients usually suffer from the combination of hypovolemia and muscle pump dysfunction (50), which makes it necessary to drink plenty of water and wear compression garments, which can reduce the venous pooling caused by insufficient peripheral venous reflux and increase peripheral blood return to the heart (98). note: 'Found by winnow, kev and lev in p021, p023. Claude judged: partial.' - paper: pmid32494413 cited: true text: full license: by verdict: partial section: Ms. Lei, Ms. Sheikh, and Dr. Raj consider quote: Lasting improvements in POTS symptoms rely on therapy regimens founded upon lifestyle changes that begin with the maintenance of high fluid and dietary salt intake, with the primary goal of augmenting plasma volume. note: 'Found by winnow, kev and lev in p035, p010. Claude judged: partial.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: partial section: Treatment > Diet quote: Increasing electrolyte and water intake was shown to decrease tachycardia in POTS patients with idiopathic forms of the disease, as a result of increased blood pressure through increasing blood volume.[24] This is also thought to be helpful in POTS patients with pooling blood and/or hypovolemia.[8] note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - edge: - midodrine_therapy - indicates - neuropathic_evidence papers: 6 evidence: - paper: pmid42037960 cited: true text: full license: by verdict: supports section: Discussion quote: Lastly, midodrine, an α1-agonist vasoconstrictor, may be particularly useful in neuropathic POTS, where impaired vascular tone leads to excessive venous pooling [7]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: In neuropathic POTS, the loss of peripheral vascular resistance due to the sympathetic denervation, especially in the lower limbs, can be addressed with the use of vasoconstrictors like midodrine [13,24]. note: 'Found by winnow, kev and lev in p093, p095. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: '4. Individualized Pharmacologic Therapies for Pediatric POTS: Predictors of Therapeutic Efficacy > 4.2. Predictors for Midodrine Efficacy in Pediatric POTS > 4.2.6. Subtypes of POTS' quote: Midodrine hydrochloride is expected to have a greater effect on improving the hemodynamic abnormalities in neuropathic POTS by promoting vasoconstriction, reducing venous capacitance, and thereby decreasing orthostatic tachycardia. However, its effects on hemodynamic improvement in hyperadrenergic POTS are limited due to the different pathophysiology compared with that of neuropathic POTS. note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Neuropathic Pots: Midodrine and Pyridostigmine' quote: In neuropathic POTS, impaired peripheral vasoconstriction caused by adrenergic denervation can lead to peripheral venous pooling (64). Midodrine, an alpha1-adrenergic agonist, can effectively constrict peripheral vessels, and increase venous return. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid23978222 cited: true text: full license: none verdict: supports section: DISCUSSION > Effects of midodrine on postural tachycardia quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23978222. Found by winnow, kev and lev in p001, p024, p028. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Vasoconstrictor Therapy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p017. Claude judged: supports.' - edge: - antihistamine_therapy - indicates - mast_cell_activation papers: 4 evidence: - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: For example, pacing is recommended care to manage energy levels and avoid PEM in ME/CFS; fluid/electrolytes, compression stockings and Mestinon to help manage OI; beta-blockers and ivabradine to aid tachycardia present in POTS; IgG for use in immune dysfunction; antihistamines (H1 and/or H2 inhibitors) and other select treatments to manage MCAS; low-dose naltrexone to manage pain; and melatonin to mitigate sleep problems. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: supports section: CASE PRESENTATION quote: The patient was referred for further evaluation to the Autonomic Nervous System Laboratory at the Instituto Nacional de Ciencias Médicas y Nutrición, where MCAS was suspected based on a medical history of rash in accordance with orthostatic intolerance symptoms. A trial with a histamine blocker (Loratadine 10 mg/12 h) was initiated, achieving remission of symptoms after a few weeks. note: 'Found by winnow, kev and lev in p024, p014. Claude judged: supports.' - paper: pmid38003876 cited: true text: full license: by verdict: supports section: 7. Mast-Cell-Directed Treatment quote: Our case series suggests that when MCAS is suspected and then diagnosed, MC-directed therapy can be effective in improving neuropsychiatric manifestations. Treatment with antihistamines, MC-stabilizing agents, and other pharmacologic modalities such as LDN, along with non-pharmacologic approaches including avoiding symptomatic triggers and adopting low-histamine and gluten/dairy-free diets, can be effective, are inexpensive, and have a low side effect profile compared to standard antidepressant and antianxiety therapies. note: 'Found by winnow, kev and lev in p012, p007, p025. Claude judged: supports.' - paper: pmid34398691 cited: true text: full license: by-nc-nd verdict: supports section: Discussion > Laboratory Recognition of MCA and Its Limitations quote: "Specifically, patients with MCA may benefit from histamine receptor (H1 and H2) blockers used in conjunction\ \ with mast cell stabilizer agents and possibly vitamin D.\n5\n, \n6\n, \n7\n, \n8\n These agents are not\ \ usually part of a typical POTS treatment regimen." note: 'Found by winnow, kev and lev in p006, p027. Claude judged: supports.' - edge: - exercise_reconditioning - indicates - long_covid papers: 3 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 7. Treatment quote: In the case of POTS related to SARS-CoV-2 infection, published cases have supported the recommendation of various non-pharmacological interventions, such as increased salt and fluid intake (unless contraindicated), waist-high compression garments, and regular and graduate-supervised exercises (84, 85). The utility of an exercise program in a recumbent or semi-recumbent position (rowing or cycling) for 8 weeks, followed by a subsequent 4-week jogging phase, has been demonstrated (86). note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 4. Management > 4.2. Exercise quote: This exercise method may be particularly favorable for patients with COVID-19-related POTS [65]. Exercises for COVID-19-related POTS management should include both aerobic and anaerobic movements, such as thigh resistance training and muscular strength training [59]. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid39198662 cited: true text: full license: by verdict: partial section: Discussion quote: The main findings of this study were that individually tailored exercise was safe and feasible for patients with PCC-POTS. note: 'Found by winnow, kev and lev in p026, p001. Claude judged: partial.' - edge: - immunomodulatory_therapy - indicates - long_covid papers: 3 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Abstract quote: The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. note: 'Found by winnow, kev and lev in p038, p040, p001. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Review quote: The most directly relevant evidence to the cognitive dimension of this research question in the source set reviewed here is provided by the first published case of plasma exchange producing documented improvement in cognitive function in a patient with long-COVID-related POTS and autoimmune neurological dysfunction (Seeley MC et al., 2023), establishing proof of concept for the cognitive-immunotherapy link even within the evidentiary constraints of a case report. note: 'Found by winnow, kev and lev in p057. Claude judged: partial.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Thus, IVIG could show potential as a possible therapeutic strategy for refractory post-viral PTS, particularly following COVID-19 infection. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - edge: - prokinetic_therapy - indicates - gi_dysmotility papers: 2 evidence: - paper: pmid42509985 cited: true text: full license: by verdict: supports section: Abstract > Abstract quote: To our knowledge, no prior case series has described metoclopramide as a targeted prokinetic bridge therapy specifically in adolescents with dysautonomia-associated GI dysmotility symptoms. note: 'Found by winnow, kev and lev in p003, p007, p011. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: Recovery > Management of POTS and Associated Conditions > Medications for Gastrointestinal Function quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p094, p095. Claude judged: partial.' - edge: - ivabradine_therapy - indicates - hyperadrenergic_evidence papers: 2 evidence: - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Discussion quote: For example, for hyperadrenergic POTS, the sympathetic output is blocked via beta-blockers, or sympathetic symptoms such as tachycardia may be combated by pharmacotherapies such ivabradine which inhibits I(f) channels. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Accordingly, inhibition of the tachycardia response with ivabradine may disrupt this feedback loop and blunt symptoms of sympathetic activation. Ivabradine may also reduce NE spillover by lowering sinoatrial node pacemaker activity, thereby decreasing sympathetic tone without the negative inotropic effects associated with beta blockers.43 note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - edge: - exercise_reconditioning - indicates - hypovolemic_evidence papers: 2 evidence: - paper: pmid31412221 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31412221. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p033, p041, p005. Claude judged: supports.' - edge: - ivabradine_therapy - indicates - long_covid papers: 2 evidence: - paper: pmid37469536 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37469536. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Management of post–COVID-19 POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p026. Claude judged: supports.' - edge: - immunomodulatory_therapy - indicates - mast_cell_activation papers: 2 evidence: - paper: pmid38003876 cited: true text: full license: by verdict: partial section: 7. Mast-Cell-Directed Treatment quote: For severe cases of MCAS, immune modulators can be helpful. These medications include hydroxyurea and various tyrosine kinase inhibitors (TKI). note: 'Found by winnow, kev and lev in p027. Claude judged: partial.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: partial section: Discussion quote: This is the first case to our knowledge where immunotherapy with IVIg led to significant and sustained improvement in MCAS as has been seen in publications of autoimmune neuromuscular diseases and a single case of POTS.9 10 Other patients with MCAS have had response in their MC symptoms to IVIg.2 note: 'Found by winnow, kev and lev in p001, p011, p014. Claude judged: partial.' - edge: - serotonergic_therapy - indicates - anxiety_depression papers: 1 evidence: - paper: pmid40454385 cited: true text: full license: by verdict: supports section: Case presentation > Tertiary hospitalization quote: The diagnosis of anxiety disorder was made based on the criteria outlined in the DSM-5, following a comprehensive clinical assessment and standardized diagnostic interviews. Based on the established efficacy of paroxetine in treating anxiety disorders with autonomic dysfunction, paroxetine hydrochloride tablets (20 mg/day, orally) were administered as anxiolytic treatment. note: 'Found by winnow, kev and lev in p008, p012, p003. Claude judged: supports.' - edge: - exercise_reconditioning - indicates - arrhythmia_differential papers: 1 evidence: - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Management: Exercise and Rehabilitation > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p146, p147. Claude judged: partial.' - edge: - pyridostigmine_therapy - indicates - autoimmune_evidence papers: 1 evidence: - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Neuropathic Pots: Midodrine and Pyridostigmine' quote: We propose that if a child with POTS is seropositive for AChR-ab, pyridostigmine should be used appropriately. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - edge: - exercise_reconditioning - indicates - cerebral_hypoperfusion_evidence papers: 1 evidence: - paper: pmid39540412 cited: true text: full license: by-nc verdict: partial section: What to Do in Clinic quote: Encouraging exercise makes sense, as through improving fitness and lower extremity muscle tone, the “skeletal muscle pump” is improved, which augments venous return to the heart and thus adequate cerebral perfusion.15,28 note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - edge: - beta_blocker_therapy - indicates - chronic_migraine papers: 1 evidence: - paper: pmid33174112 cited: true text: full license: none verdict: supports section: Discussion > Implications for Diagnosis and Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33174112. Found by winnow, kev and lev in p030. Claude judged: supports.' - edge: - lifestyle_modification - indicates - gi_dysmotility papers: 1 evidence: - paper: pmid42509985 cited: true text: full license: by verdict: partial section: 2. Case Presentations > 2.1. Case 1—13-Year-Old Female with Dysautonomia and Chronic Nausea quote: Concurrent interventions included amitriptyline 10 mg nightly (continued from prior), magnesium glycinate 240 mg daily, Iberogast, ginger capsules 500 mg twice daily, dietary modifications (small frequent low-fat meals, improved breakfast intake), hydration and salt expansion, and compression garment use. note: 'Found by winnow, kev and lev in p011, p015, p022. Claude judged: partial.' - edge: - compression_therapy - indicates - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid38260095 cited: true text: full license: by verdict: partial section: 4 Discussion quote: Considering our results of multiple regression analysis, abdominal and lower-extremity compression may be a beneficial treatment for individuals with hyperadrenergic POTS. Further studies are needed to examine whether abdominal and lower-extremity compression can reduce these individuals’ excessive central sympathetic activity and orthostatic tachycardia. note: 'Found by winnow, kev and lev in p032. Claude judged: partial.' - edge: - compression_therapy - indicates - hypermobility_heds papers: 1 evidence: - paper: pmid36694653 cited: true text: full license: by verdict: partial section: DISCUSSION quote: The use of DEFO garments could be considered as an intervention to allow improved function in people with hEDS and PoTs. A garment that encompasses the abdomen and lower body, and exerts a compressive force, has previously been shown to reduce heart rate and improve PoTS symptoms in adult patients. note: 'Found by winnow, kev and lev in p015, p013. Claude judged: partial.' - edge: - compression_therapy - indicates - hypovolemic_evidence papers: 1 evidence: - paper: pmid38328599 cited: true text: full license: by verdict: supports section: Summary figure quote: Patients with hypovolemic POTS may increase circulating blood volume through exercise, hydration, salt loading, and compression stockings. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - edge: - auricular_vagus_nerve_stimulation - indicates - long_covid papers: 1 evidence: - paper: pmid40014480 cited: true text: full license: by verdict: supports section: Discussion > LL‐TS and POTS quote: Therefore, that LL‐TS is a noninvasive neuromodulation in autonomic balance for individuals with POTS following post‐acute COVID‐19 infection. note: 'Found by winnow, kev and lev in p025, p003, p007. Claude judged: supports.' - edge: - compression_therapy - indicates - long_covid papers: 1 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 7. Treatment quote: In the case of POTS related to SARS-CoV-2 infection, published cases have supported the recommendation of various non-pharmacological interventions, such as increased salt and fluid intake (unless contraindicated), waist-high compression garments, and regular and graduate-supervised exercises (84, 85). note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - edge: - lifestyle_modification - indicates - long_covid papers: 1 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 7. Treatment quote: It is advisable to avoid situations that can exacerbate symptoms, which has also been shown to be beneficial in POTS after SARS-CoV-2 infection (Table 1) (17, 87, 88). note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - compression_therapy - indicates - neuropathic_evidence papers: 1 evidence: - paper: pmid31412221 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31412221. Found by winnow, kev and lev in p001. Claude judged: supports.' - edge: - exercise_reconditioning - indicates - neuropathic_evidence papers: 1 evidence: - paper: pmid34674068 cited: true text: full license: by verdict: partial section: Discussion quote: 'These findings taken together support regular exercise as a treatment modality in neuropathic POTS [34] and at least partially explain its beneficial effect: Training increases hyperpolarization in the long term and reduces muscle membrane depolarization.' note: 'Found by winnow, kev and lev in p022. Claude judged: partial.' - edge: - immunomodulatory_therapy - indicates - neuropathic_evidence papers: 1 evidence: - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Case description and results quote: 18 months after the onset of symptoms, an autoimmune mediated, neuropathic POTS refractory to symptomatic treatment was diagnosed. A dose of 2 g/kg body weight IVIg over 5 days was administered 33 months after the first manifestation of symptoms. note: 'Found by winnow, kev and lev in p005, p010, p017. Claude judged: partial.' - edge: - lifestyle_modification - indicates - postinfectious_evidence papers: 1 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 7. Treatment quote: It is advisable to avoid situations that can exacerbate symptoms, which has also been shown to be beneficial in POTS after SARS-CoV-2 infection (Table 1) (17, 87, 88). note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - exercise_reconditioning - indicates - secondary_sinus_tachycardia papers: 1 evidence: - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Management: Exercise and Rehabilitation > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p147, p146. Claude judged: partial.' - edge: - immunomodulatory_therapy - indicates - systemic_autoimmune_disease papers: 1 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Immunotherapies > Potential immunologic therapies for POTS, other common autonomic disorders, and Long COVID quote: These therapies may be used either as a last resort in patients who failed standard non-pharmacologic and pharmacologic therapies or as a first-line treatment in patients with POTS and OCADs of suspected autoimmune or inflammatory etiologies, or comorbid SFN, UCTD, and other systemic autoimmune disorders. note: 'Found by winnow, kev and lev in p029, p038. Claude judged: supports.' - edge: - beta_blocker_therapy - treats - pots papers: 88 evidence: - paper: pmid42605371 cited: true text: full license: by verdict: supports section: Review quote: Additional support for autoimmune or inflammatory subgroups of POTS comes from the fact that some patients experience persistent cognitive symptoms despite treatment. Common treatment options that may alter heart rate or blood pressure without eliminating autoantibodies, lessening brain inflammation, or unblocking small vessels include beta-blockers, ivabradine, and midodrine. note: 'Found by winnow, kev and lev in p019, p056. Claude judged: supports.' - paper: pmid42591853 cited: true text: full license: by verdict: supports section: ME/CFS as a low output syndrome due to small heart > Is POTS a cause of OI? quote: Low-dose oral propranolol (20 mg) significantly attenuated tachycardia and improved symptoms in POTS (64). note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: Beta-blockers may be used to reduce sinus tachycardia and palpitations in POTS. One study observed that low-dose oral propranolol attenuated tachycardia in POTS and elicited a better response than high-dose oral propranolol, which did not improve or may have worsened symptoms [5]. note: 'Found by winnow, kev and lev in p091, p100. Claude judged: supports.' - paper: pmid42132710 cited: true text: full license: by verdict: supports section: Body quote: Propranolol is a nonselective beta-blocker that has been shown to mitigate tachycardia and symptoms in patients with POTS, but may have off-target side effects due to the broad distribution of beta-adrenergic receptors throughout the body.6, 7, 8 note: 'Found by winnow, kev and lev in p005, p007, p052. Claude judged: supports.' - paper: pmid41827215 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Beta-blockers (e.g., metoprolol) are commonly used in the treatment of pediatric POTS, as they can reduce sympathetic nerve activity and/or lower plasma catecholamine levels [8,9]. note: 'Found by winnow, kev and lev in p001, p011, p002. Claude judged: supports.' - paper: pmid41767063 cited: true text: full license: by verdict: supports section: Discussion quote: 'Therapeutic interventions for post‐SCI POTS remain limited in the literature. Based on this case and prior reports [5], syncope can be cured by multiple management, including: aggressive infection control, increased fluid intake, abdominal binder and compression stocking application during mobilization, slow transfer protocols with gradated torso elevation, low‐dose metoprolol (12.5 mg twice daily), and systematic rehabilitation.' note: 'Found by winnow, kev and lev in p019, p028, p026. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: Beta-adrenergic antagonists like bisoprolol and low-dose propranolol control the tachycardia and often provide symptomatic relief in POTS [22]. note: 'Found by winnow, kev and lev in p092, p095. Claude judged: supports.' - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p009, p032, p039. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Results > Pharmacological interventions > β-Adrenergic blocking agents quote: In 49 children, the application of metoprolol (0.5 mg/kg body weight, two times per day) significantly attenuated HR increment from the supine to the standing position after 1.5–3 months (p < 0.001) and led to an improvement in symptoms [33]. note: 'Found by winnow, kev and lev in p032, p034, p035. Claude judged: supports.' - paper: pmid40681233 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Central sympatholytic agents such as methyldopa or clonidine may also be used, and if these are not tolerated, peripheral β-adrenergic therapies are considered.4 Specifically, β-adrenergic blockers are commonly used in cardiology clinics to control tachycardia.4 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Results > Treatments Impact Core Disease Symptoms Differently. quote: As expected, compression stockings and Mestinon most frequently improved symptoms of POTS (63.7% and 56.9%, respectively), while beta blockers and ivabradine primarily alleviated POTS symptoms (66.0%). note: 'Found by winnow, kev and lev in p018, p033. Claude judged: supports.' - paper: pmid40626134 cited: true text: full license: by verdict: supports section: THE CURRENT STATUS OF INDIVIDUALIZED TREATMENT OF POTS IN CHILDREN > β‐Adrenergic receptor blockers in treating children with POTS quote: Tachycardia associated with the orthostatic position is a clinical feature of POTS. β‐Adrenergic receptor blockers can block the effect of excessively increased catecholamine levels in some patients to alleviate symptoms. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 4 Discussion > 4.5 Rationality of current treatment approaches quote: 'ANS modulation therapy: Given the role of abnormal ANS function in POTS, medications such as β-blockers (e.g., metoprolol) may be considered to control excessive heart rate increases [20,66,67].' note: 'Found by winnow, kev and lev in p062. Claude judged: supports.' - paper: pmid40520610 cited: true text: full license: by verdict: supports section: Results quote: In 8 of these 39 cases, this included using a beta blocker, which can be effective for both PoTS and migraine. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid40437589 cited: true text: full license: by verdict: supports section: Materials and methods > Treatment and follow-up quote: In addition, patients with VVS responses took oral rehydration salts (ORS, 250 mL, twice a day), and patients with POTS and OHT took metoprolol (0.5-1.0 mg/(kg·d) was administered orally in two divided doses) for treatment [12, 13]. note: 'Found by winnow, kev and lev in p012, p020, p027. Claude judged: supports.' - paper: pmid39882369 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). note: 'Found by winnow, kev and lev in p004, p016, p023. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Anecdotally, we found that treatment of POTS with therapies targeting sympathetic overactivity, hypovolemia, and mast cell hyperactivity has been more efficacious than neuropathic pain medications. These therapies consist of beta blockers; increased oral fluids and salt intake; intravenous fluids; and other medications, such as pyridostigmine, which enhances parasympathetic transmission; midodrine, which increases vasoconstriction and therefore improves venous return and cerebral perfusion; and benzodiazepines, which may reduce IT via GABA-mediated actions in the central autonomic networks (Table 1). note: 'Found by winnow, kev and lev in p012, p008. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Pharmacologic Therapies > Medications That Target Rapid Heart Rate quote: β-blockers are frequently used for tachycardia in POTS patients. These medications reduce cardiac baroreceptor activation, lower serum norepinephrine levels, and inhibit sympathetic nerve activity.[66] note: 'Found by winnow, kev and lev in p051. Claude judged: supports.' - paper: pmid39552985 cited: true text: full license: by verdict: supports section: Abstract quote: The patient made a remarkable functional recovery from POTS, as she responded well to pharmacotherapy, primarily beta-blockers, along with lifestyle modifications. note: 'Found by winnow, kev and lev in p001, p009, p031. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Clinical management quote: Eldokla et al. (2022) reported on five patients who developed POTS after mRNA vaccination, managed with medications like ivabradine, metoprolol, fludrocortisone, and propranolol [24]. note: 'Found by winnow, kev and lev in p021, p023, p026. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.5. Treatments for COVID-19-Related POTS Due to Increased Norepinephrine in the Blood quote: β-blockers can inhibit β-ARs that react to norepinephrine or epinephrine secreted from sympathetic nerve endings. The β-blockers help reduce tachycardia, decrease excess epinephrine, and alleviate orthostatic intolerance [52]. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid38240001 cited: true text: full license: by verdict: supports section: METHODS > Treatment options quote: As a standard treatment for POTS, patients were counseled to consume ≥10 g of salt and 2–3 L of water, except for those with hypertension and older people; instructed to wear elastic compression stockings up to the thighs; and prescribed bisoprolol, a β1‐selective blocker, once daily. note: 'Found by winnow, kev and lev in p015, p019. Claude judged: supports.' - paper: pmid38033543 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: In the Poincaré plot, a T < 573.9 ms combined with an L/T > 2.9 helps predict good outcomes of using metoprolol to treat pediatric POTS. note: 'Found by winnow, kev and lev in p004, p012, p024. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: Abstract quote: The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. note: 'Found by winnow, kev and lev in p001, p025. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: Beta-adrenoreceptor antagonists like propranolol, metoprolol, and bisoprolol are the most often utilized medications for treating POTS, with an equal efficacy between propranolol and bisoprolol. note: 'Found by winnow, kev and lev in p014, p001, p021. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: '4. Individualized Pharmacologic Therapies for Pediatric POTS: Predictors of Therapeutic Efficacy' quote: The pharmacological treatment options include oral rehydration salts (ORS), midodrine hydrochloride, metoprolol, fludrocortisone and some other specialized therapies, such as droxidopa, desmopressin, erythropoietin and intravenous immunoglobulin (IVIG) [30,47,48,49,50]. note: 'Found by winnow, kev and lev in p031, p014, p035. Claude judged: supports.' - paper: pmid37443510 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Metoprolol is effective for pediatric POTS at an initial dose of 0.5 mg/(kg·d) divided into 2 administrations. The total dose of the drug should not exceed 2 mg/(kg·d). note: 'Found by winnow, kev and lev in p004, p024, p001. Claude judged: supports.' - paper: pmid37313107 cited: true text: full license: by verdict: supports section: Introduction and background quote: Pharmacologic therapies have been explored in minimizing symptoms and increasing functional ability in POTS patients [2]. Treatment targets have focused on reducing heart rate (beta-blockers), increasing cardiac output (increase in salt intake), or increasing blood pressure (midodrine). note: 'Found by winnow, kev and lev in p004, p030. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports > Pharmacological Therapies quote: Beta blockers such as propranolol are particularly favored in hyperadrenergic forms of POTS. Pre-emptive administration prior to exercise has been reported to be effective in improving exercise capacity.63 note: 'Found by winnow, kev and lev in p035, p022, p030. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Beta-blockers: Both beta-1 selective and nonselective beta-blockers have been used in POTS management. Beta-blockers help by reducing tachycardia and the hyperadrenergic state and improving exercise intolerance and orthostatic intolerance.' note: 'Found by winnow, kev and lev in p062, p063. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: While there is no universal pharmacological guideline for POTS, medications such as fludrocortisone, pyridostigmine, midodrine, and beta blockers can help with its management, depending on the cause [2]. Beta blockers can blunt elevations in heart rate. note: 'Found by winnow, kev and lev in p017, p004. Claude judged: supports.' - paper: pmid36781629 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: It had an excellent predictive value of the therapeutic effect of metoprolol on POTS among children and adolescents. note: 'Found by winnow, kev and lev in p002, p004, p019. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Case summary > Management quote: Beta-blockers have been recommended to lower standing heart rate and reduce symptoms of tachycardia and palpitations,1 and thus metoprolol was also used in this case. note: 'Found by winnow, kev and lev in p018, p017, p020. Claude judged: supports.' - paper: pmid36187012 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: The baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS. note: 'Found by winnow, kev and lev in p022, p002, p004. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.4. Physiological Predictors for the Efficacy of Metoprolol in Pediatric POTS quote: Beta-adrenoceptor blockers are often applied in the management of pediatric POTS patients. They inhibit sympathetic nervous system activity and reduce stimulation of the heart rate and cardiac baroreceptors, thereby blocking the effects of increased blood catecholamine levels. note: 'Found by winnow, kev and lev in p038, p040, p042. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How is POTS treated? > Pharmacological treatments quote: A 2009 randomized crossover study found that low-dose oral propranolol improved tachycardia and symptoms on standing,45 and a small, randomized, double-blind study in 2013 showed improved exercise capacity46 in patients with POTS. Propranolol has a short half-life and requires dosing 4 times per day. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid35176758 cited: true text: full license: by verdict: supports section: Proposed model for investigation and management of cardiovascular sequelae and long COVID quote: The management of POTS centres around accurate diagnosis following specialist assessment, correction of reversible causes (dehydration, heat), optimization of chronic disease management, and patient education. In some patients with ongoing palpitations, beta-blockers can be helpful in treating symptoms.234 note: 'Found by winnow, kev and lev in p043. Claude judged: supports.' - paper: pmid35127870 cited: true text: full license: by verdict: supports section: Introduction quote: Beta-adrenoceptor blocker metoprolol was currently one of the main drugs for the treatment of children with POTS. note: 'Found by winnow, kev and lev in p002, p003, p005. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Treatment > Pharmacologic interventions quote: The CCS position statement on POTS states that the most commonly used medications for the management of POTS include propranolol, midodrine, pyridostigmine, fludrocortisone, ivabradine, clonidine, methyldopa, and occasional 0.9% sodium chloride I.V. infusions.7 All are off-label for the treatment of POTS in the US. note: 'Found by winnow, kev and lev in p034, p035. Claude judged: supports.' - paper: pmid34847948 cited: true text: full license: by verdict: supports section: Discussion quote: In POTS, β-adrenergic blockers have been reported to improve symptoms [27, 28]. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Possible Treatment for Post-COVID Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid34387611 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Beta-blockers are important treatment option for POTS in children and adolescents,[7,8] but they only improve symptoms in approximately 57.10% to 57.89% of children.[9,10] note: 'Found by winnow, kev and lev in p002, p004, p005. Claude judged: supports.' - paper: pmid34353826 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34353826. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Pharmacologic management > β-blockers quote: In a randomized crossover study of 54 patients with POTS who were trialed with 20 mg of propranolol versus placebo, orthostatic heart rates were significantly lower with propranolol use as compared with among those on placebo.22 In addition, symptom burden was improved in patients on low-dose propranolol relative to placebo therapy.22 note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Pharmacologic management of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid34035985 cited: true text: full license: by verdict: supports section: Discussion quote: Low-dose propranolol has also demonstrated efficacy in reducing tachycardia and achieving symptomatic control in POTS. note: 'Found by winnow, kev and lev in p010, p014. Claude judged: supports.' - paper: pmid33623665 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Pharmacological therapy is considered on an individual basis, consisting of beta-blockers to blunt orthostatic increases in heart rate, alpha-adrenergic agents to increase peripheral vascular resistance, mineralocorticoids to increase blood volume and serotonin reuptake inhibitors to improve serotonin regulation [4]. note: 'Found by winnow, kev and lev in p007, p001, p009. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Management Strategies for Pots in Children and Adolescents > Pharmacological Treatment quote: In 2009, a single-center retrospective chart analysis and follow-up conducted by the Mayo Clinic showed that adolescents with POTS taking β-blockers were more likely to have an improvement in symptoms than those taking midodrine (116), suggesting that β-blockers were effective for young POTS patients. β1-Selective blockers are useful for “hyperadrenergic” subtypes of POTS patients (96). note: 'Found by winnow, kev and lev in p027, p022. Claude judged: supports.' - paper: pmid32673517 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Our results also confirmed the efficacy of low‐dose propranolol in reducing orthostatic tachycardia in POTS. note: 'Found by winnow, kev and lev in p017, p033, p036. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Hyperadrenergic Pots: β-Blockers' quote: Propranolol, a non-selective β-blocker, can pass the blood-brain barrier. Thus, it is considered to work better than other β-blockers in the treatment of POTS (71). note: 'Found by winnow, kev and lev in p028, p017, p027. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Cannom assesses quote: In the uncomplicated POTS patient who is symptomatic due to orthostatic tachycardia, the traditional approach has been the use of a β-blocker in association with hydration, salt, and compression stockings. note: 'Found by winnow, kev and lev in p011, p048. Claude judged: supports.' - paper: pmid32489723 cited: true text: full license: by verdict: supports section: Introduction and background quote: Pharmacological therapies include beta-blockers (first line), alpha-agonists (first or second line), mineralocorticoids (second line), selective serotonin reuptake inhibitors (SSRIs), and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs), and rarely used drugs include pyridostigmine, desmopressin, and erythropoietin [4,11]. note: 'Found by winnow, kev and lev in p004, p024. Claude judged: supports.' - paper: pmid32464225 cited: true text: abstract license: none verdict: supports section: Abstract > Study Design quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32464225. Found by winnow, kev and lev in p003, p001, p002. Claude judged: supports.' - paper: pmid32112609 cited: true text: full license: by verdict: supports section: SUBJECTS AND METHOD > Methods > Treatment quote: 'Health education was taken in the 100 children and adolescents with POTS, including psychological guidance of children and their families, avoidance of syncope inducement, drinking more water, keeping urine clear (urination twice in the morning and afternoon), assuring enough sleep time (>8 hr/day), erect training (standing against the wall, 2 times/day, 30 min/times), oral rehydration salts Ⅲ (made in Xi ''an Anjian Pharmaceutical Co., LTD, approval number: H20090205) 5.125 g/bag (each bag was divided into 250 ml water for oral administration, 2 bags/day; halve the dose for children under 6 years old) and oral metoprolol (from Astrazeneca Pharmaceutical Co., LTD, production batch number: 326201), 0.5 ~ 1.0 mg/kg, oral, 2 times/day.' note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Challenge II: Lack Of Standardized Approaches To Physical Rehabilitation And Psychopharmacology > Pharmacological Treatment Approaches' quote: Beta-blockers as a class have been shown to improve orthostatic symptoms in some patients with POTS by decreasing tachycardia through improved heart rate control. For pediatric patients, propranolol, metoprolol, and labetalol have been used. note: 'Found by winnow, kev and lev in p005, p018. Claude judged: supports.' - paper: pmid31788462 cited: true text: full license: by verdict: supports section: Abstract quote: 'Conclusion: β-blockers are effective in treating POTS in children and adolescents, alleviating orthostatic intolerance, and improving hemodynamic abnormalities.' note: 'Found by winnow, kev and lev in p002, p003, p005. Claude judged: supports.' - paper: pmid31780890 cited: true text: full license: by verdict: supports section: Introduction quote: A beta-adrenoceptor blocker (β-blocker) is commonly used for treating POTS in children (Kernan and Tobias, 2010; Bryarly et al., 2019). note: 'Found by winnow, kev and lev in p005, p002, p004. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Approach to therapy for patients with POTS > Prognosis quote: A prospective, longitudinal study of 56 patients who were treated at the Mayo clinic with a combination of nonpharmacologic interventions and β-blockers (54%), fludrocortisone (24%) or midodrine (17%) found improvement in 70% of patients, while 30% became worse after 1 year of treatment.82 note: 'Found by winnow, kev and lev in p024, p026. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: THE INDIVIDUALIZED TREATMENT OF POSTURAL TACHYCARDIA SYNDROME quote: Currently, based on the possible pathogenesis, the first-line treatments for POTS mainly include oral rehydration salts (ORS), beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. note: 'Found by winnow, kev and lev in p013, p004, p018. Claude judged: supports.' - paper: pmid26241226 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: Other drugs which can also be therapeutically beneficial in patients with POTS are (1) drugs that increase peripheral vascular resistance such as midodrine, a prodrug whose active metabolite is an α-adrenoceptor antagonist, and somatostatin analogs; (2) drugs that can modify the central and peripheral activity of the sympathetic nervous system such as β-adrenoceptor antagonists (mainly propranolol), serotonin and norepinephrine uptake inhibitors, and combined α- and β-adrenoceptor antagonists; and (3) drugs that reduce the sympathetic tone such as clonidine.2,3,9 note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid26199795 cited: true text: full license: none verdict: supports section: Case Description > Case 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26199795. Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p039. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid25811760 cited: true text: full license: by verdict: supports section: Discussion quote: Metoprolol is one of the main drugs for POTS currently. It is used to treat POTS by blocking β-adrenoceptor, and as a result, blocking high levels of catecholamines in circulation, and lowering the heart rate [3]. note: 'Found by winnow, kev and lev in p001, p002, p018. Claude judged: supports.' - paper: pmid25204388 cited: true text: full license: by verdict: supports section: Discussion quote: Raj et al. reported that low-dose oral propranolol significantly attenuated tachycardia and improved symptoms in POTS, and higher-dose propranolol did not further improve, and might worsen symptoms [8]. Arnold et al. also found recently that propranolol could improve HR control and exercise capacity in POTS when given at the low doses of propranolol for treatment [10]. note: 'Found by winnow, kev and lev in p014, p019, p002. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p037, p042. Claude judged: supports.' - paper: pmid23616163 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23616163. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Sympatholysis quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p016, p019. Claude judged: supports.' - paper: pmid21977261 cited: true text: full license: none verdict: supports section: CASE REPORT quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p018, p012, p016. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: supports section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038, p035. Claude judged: supports.' - paper: pmid21690484 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21690484. Found by winnow, kev and lev in p001, p002, p023. Claude judged: supports.' - paper: pmid21686452 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21686452. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid20860911 cited: true text: abstract license: none verdict: supports section: Abstract > Case History quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20860911. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid20668563 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Additionally, once the primary pathophysiologic defect (vasodilatation and relative hypovolemia) is corrected, β-adrenergic antagonists may be used to primarily treat the reflex tachycardia. In our patient, pharmacologic therapy include both midodrine to treat the loss of vascular tone and metoprolol to prevent reflex tachycardia.[411] note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid19687359 cited: true text: full license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19687359. Found by winnow, kev and lev in p002, p003, p022. Claude judged: supports.' - paper: pmid11206727 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11206727. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid11201632 cited: true text: abstract license: none verdict: supports section: Abstract > Methods And Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11201632. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid11198485 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11198485. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid10750641 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 10750641. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid10406593 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 10406593. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid40624434 cited: true text: full license: by verdict: partial section: Treatment quote: Pharmacotherapy includes first-line medications such as beta-blockers, which decrease resting and postural tachycardia by inhibiting beta-1 adrenergic receptors and reducing sympathetic overactivity; fludrocortisone, a mineralocorticoid that augments retention of water and sodium and expands plasma volume; midodrine, which is an apha-1 agonist that causes vasoconstriction and increased peripheral resistance, and other commonly used medications for the orthostatic intolerance, tachycardia and fatigue, such as pyridostigmine, ivabradine, clonidine, guanfacine, modafinil, methylphenidate and others [6, 24, 25]. note: 'Found by winnow, kev and lev in p009, p021, p001. Claude judged: partial.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Given our findings suggesting a central role for adrenergic signaling in the development of POTS post-HSCT, treatment with a nonselective β-AR blocker such as propranolol may be appropriate. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid38867988 cited: true text: full license: by-nc verdict: partial section: Case presentation > History quote: Additionally, mast cell activation syndrome (MCAS) was suspected given relief with cetirizine. In addition to supportive measures, diltiazem was transitioned to propranolol (20 mg TID) with improved effect. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid36158335 cited: true text: full license: by verdict: partial section: Case presentation quote: At the two-month follow-up, the patient was prescribed metoprolol 25mg and instructed to titrate up to 50mg for symptomatic relief of tachycardia, diaphoresis, headaches, and near syncopal events. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: partial.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: partial section: 'Patient #3' quote: The patient received propranolol 10 mg ×3 times a day and pyridostigmine 10 mg ×3, the latter due to severe fatigue and muscle weakness. In addition to typical POTS symptoms he developed nausea, orbital edema, and gastrointestinal symptoms (Figure 6). note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid19207771 cited: true text: full license: none verdict: partial section: Management > Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid17933281 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 17933281. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - exercise_reconditioning - treats - pots papers: 58 evidence: - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: One study observed that graded exercise therapy in a semi-recumbent position to avoid upright posture, such as recumbent bike, swimming, and rowing, improved symptoms by increasing the aldosterone-to-renin ratio and decreasing heart rate [61]. note: 'Found by winnow, kev and lev in p091, p100. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Conclusions quote: Compression garments, physical training and salt supplementation have been shown to have beneficial effects on symptom burden and/or hemodynamics in patients with POTS and should be the first therapeutic approach in patients with POTS. note: 'Found by winnow, kev and lev in p086, p015, p022. Claude judged: supports.' - paper: pmid41166031 cited: true text: full license: by verdict: supports section: Introduction quote: Exercise is considered a first-line treatment for POTS and is recommended regardless of presumed etiology. While the first studies of exercise in POTS framed it as countering deconditioning, there has since been significant debate as to whether deconditioning is a primary cause of POTS or is more likely to occur secondary to the disorder [3]. note: 'Found by winnow, kev and lev in p007, p006, p027. Claude judged: supports.' - paper: pmid40944681 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Case Summary quote: POTS was exacerbated in a 28-year-old woman with obesity after using tirzepatide for weight reduction. Her condition was effectively treated with progressive exercise training and counseling, which reduced supine and standing heart rates to normal values, before starting tirzepatide. note: 'Found by winnow, kev and lev in p006, p002. Claude judged: supports.' - paper: pmid40538940 cited: true text: full license: by verdict: supports section: Introduction quote: Exercise training is already recommended as a treatment for PoTS, especially for its prevention and for the improvement of deconditioning (1, 4). note: 'Found by winnow, kev and lev in p004, p009, p025. Claude judged: supports.' - paper: pmid40365455 cited: true text: full license: by verdict: supports section: Introduction quote: While medications are often used, structured therapeutic exercise – generally beginning with aerobic and strength training using recumbent positioning, gradually building toward longer durations and a more upright posture – remains a cornerstone of current consensus-driven POTS management.5,6 note: 'Found by winnow, kev and lev in p007, p025, p026. Claude judged: supports.' - paper: pmid40125494 cited: true text: full license: by verdict: supports section: Discussion quote: Current standard treatments begin with the initiation of non-pharmacologic interventions, such as liberal dietary salt and water intake to increase blood volume, limiting caffeine intake, a daily exercise program for physical reconditioning, and wearing compression stockings.1,5 note: 'Found by winnow, kev and lev in p008, p014. Claude judged: supports.' - paper: pmid39822199 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: Exercise is a well-documented, nonpharmacologic treatment for individuals with autonomic dysfunction and associated orthostatic intolerance, such as postural tachycardia syndrome and related disorders. Exercise has been shown to increase blood volume, reverse cardiovascular deconditioning, and improve quality of life. note: 'Found by winnow, kev and lev in p001, p017, p004. Claude judged: supports.' - paper: pmid39678714 cited: true text: full license: by-nc verdict: supports section: Results quote: The increase in HR from supine to 10-minute stand and the quality of life improved significantly after the intervention. The study concluded that this exercise program was effective in treating POTS and can be applied in community setting with physician supervision. note: 'Found by winnow, kev and lev in p030, p031, p034. Claude judged: supports.' - paper: pmid39597891 cited: true text: full license: by verdict: supports section: Abstract quote: Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p015, p001, p007. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Non-pharmacologic Therapies quote: The Levine Protocol is a 3-month exercise program that has shown efficacy in lowering heart rates and improving cardiac output in POTS patients.[61] note: 'Found by winnow, kev and lev in p045. Claude judged: supports.' - paper: pmid39540412 cited: true text: full license: by-nc verdict: supports section: What to Do in Clinic quote: At follow-up, 71% of the patients significantly improved to the point that they no longer met the diagnostic criteria for POTS. Perhaps even more encouraging is that this improvement remained true 6 to 12 months after the exercise intervention, based on clinical follow-up. note: 'Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Non-pharmacological treatment quote: Physical exercise plays a critical role in the management of POTS, particularly when tailored to the patient’s subtype and tolerance levels. Initial exercise regimens should involve low-intensity, recumbent activities such as rowing or swimming to minimize excessive upright positioning, progressing gradually over a three-month period [41]. note: 'Found by winnow, kev and lev in p029, p030. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.2. Exercise quote: Gradually increasing exercise intensity can also relieve POTS-related symptoms and reduce abnormally increased heart rate in the standing position. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid38958137 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: "However, exercise interventions, such as the Levine protocol\n31\n and other nonspecified exercise activities,\ \ as well as dietary changes were used most often, still being used at the time of survey completion, and\ \ perceived by patients to be the most effective. Indeed, exercise has been proven to successfully reduce\ \ POTS symptoms." note: 'Found by winnow, kev and lev in p043, p046. Claude judged: supports.' - paper: pmid38953100 cited: true text: full license: by-nc-nd verdict: supports section: Physical activity in FND and comorbid disorders > Physical activity in postural orthostatic tachycardia syndrome quote: In POTS, exercise intolerance directly correlates with reduced functionality, with 61 % of patients reporting the inability to tolerate more than thirty minutes of exercise [70]. Physical reconditioning with exercise training is an important component of treatment. note: 'Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid38162438 cited: true text: full license: by verdict: supports section: Discussion > Postural orthostatic tachycardia syndrome quote: Progressive exercise training to build endurance and increase leg resistance is integral to the treatment plan. The exercise program may initially be recumbent such as rowing, cycling, or swimming, progressing to upright exercise, and patients should be educated that they may initially feel worse. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid37598401 cited: true text: full license: by verdict: supports section: Introduction quote: Previous research has demonstrated that a 3-month exercise training program can help treat the cardiac origins of the condition by increasing blood volume, left ventricular mass, and consequently stroke volume to improve aerobic fitness [9]. Most importantly starting and maintaining an active lifestyle can be the key to reducing or eliminating symptoms [10]. note: 'Found by winnow, kev and lev in p006, p028, p030. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Discussion quote: Every POTS management plan should include exercise training. The exercise protocol starts with recumbent aerobic and resistance training progressing to upright exercises. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: Incremental aerobic exercise programs should be implemented for all patients with POTS. Despite the patient’s intolerance to upright position exercises, patients have shown progress in a recumbent or semi-recumbent position such as recumbent biking, swimming, or machine rowing. note: 'Found by winnow, kev and lev in p008, p004. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports > Non-Pharmacological Therapies quote: Exercise training has proven quite effective overall in improving physical conditioning, soleal muscle pump functioning as well as quality of life.65 Exercise prescriptions have proven effective in COVID-POTS. note: 'Found by winnow, kev and lev in p032, p030. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Physical exercise: Studies have demonstrated improvement of POTS symptoms with aerobic exercise programs with gradual increments as tolerated [12,63,69,70].' note: 'Found by winnow, kev and lev in p057. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Results > POTS management quote: Regular, structured, progressive, and supervised exercises have been described as effective non-pharmacological treatments to improve POTS-related symptoms9,21,30,31. However, given the possible activity-induced symptoms, exercise should be restricted to no upright exercises such as swimming, rowing machines, and recumbent cycles9,21,24,30,31. note: 'Found by winnow, kev and lev in p013, p029. Claude judged: supports.' - paper: pmid35697326 cited: true text: full license: none verdict: supports section: Supportive Lifestyle Practices > Physical Activity quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35697326. Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Treatment > Nonpharmacologic interventions quote: Short-term exercise of at least 30 minutes every other day for 3 months was found to decrease heart rate and increase baroreflex sensitivity in patients with POTS.22 It is important that the patient start a graduated exercise plan, beginning with recumbent exercises, and take caution not to overexert.14 note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Non-pharmacologic management of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p030, p028. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Num estudo que realizou um registro internacional de SPOT, o condicionamento físico progressivo demonstrou expansão volêmica e aumentou a área cardíaca dos pacientes, resultando numa melhora significativa dos sintomas. Nesse estudo, 71% dos pacientes que completaram o programa de treinamento ficaram livres do diagnóstico de SPOT. note: 'Found by winnow, kev and lev in p128, p129, p166. Claude judged: supports.' - paper: pmid33482385 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33482385. Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Our findings are, therefore, highly consistent with studies53,54 indicating that exercise reconditioning may be the ideal treatment for POTS because it increases parasympathetic and decreases sympathetic cardiac activity. note: 'Found by winnow, kev and lev in p057. Claude judged: supports.' - paper: pmid33083000 cited: true text: full license: by verdict: supports section: Background quote: Exercise training is also advocated as an essential component of POTS treatment [1]. note: 'Found by winnow, kev and lev in p024, p007, p008. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: Non-Pharmacological Treatments quote: Some investigators have found that a regular, short-term progressive physical-exercise program leads to improved symptoms in POTS patients (47). Such a regimen consists of rowing on a machine, swimming, recumbent and upright biking, and treadmill walking. note: 'Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid32489723 cited: true text: full license: by verdict: supports section: Review quote: The primary aspect of POTS treatment is exercise conditioning and all patients are recommended to start a gradual physical exercise regimen [5]. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid32284866 cited: true text: full license: by-nc verdict: supports section: Discussion quote: 'Progressive exercise training has been demonstrated to lead to improvement or resolution of POTS.29 However, pharmacotherapy with medications such as propranolol, midodrine or fludrocortisone is often required, especially where symptoms are severe.20' note: 'Found by winnow, kev and lev in p010, p017. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Challenge II: Lack Of Standardized Approaches To Physical Rehabilitation And Psychopharmacology > Physical Rehabilitation Approaches' quote: Exercise and normalization of functional activities are major components in the treatment of POTS, and it is recommended that patients utilize a rehabilitation specialist (e.g., physical or occupational therapist) for implementation and progression.1 note: 'Found by winnow, kev and lev in p014, p015, p005. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: 2. EXERCISE TRAINING quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p001, p005, p009. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: MANAGEMENT OF POTS quote: Some individuals with POTS respond favorably to progressive exercise training, resulting in gradual increase in blood volume, exercise capacity, and stroke volume along with improved left ventricular diastolic function.47–50 Recommendation for exercise to manage POTS stems from a study that engaged primary care physicians in the distribution of a 3-month unsupervised exercise program, referred to as the Levine protocol, for patients with POTS.51 note: 'Found by winnow, kev and lev in p019, p018, p023. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: THE INDIVIDUALIZED TREATMENT OF POSTURAL TACHYCARDIA SYNDROME quote: Children with POTS and their parents should be informed of the potential aggravating or precipitating factors, such as the sudden head-up postural change, prolonged standing posture, and the high environmental temperatures. Besides that, exercise training that could improve the autonomic tone is also recommended.[2021] note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Non-Pharmacological Treatment of POTS > Exercise in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p036, p037. Claude judged: supports.' - paper: pmid25487551 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25487551. Found by winnow, kev and lev in p003, p008, p009. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: 'Treatment approaches: Addressing neurohormonal imbalances (Table 1) > Hypovolemia and renin-angiotensin-aldosterone paradox—volume loading' quote: The 3 month exercise program was able to increase the aldosterone:renin ratios well as the plasma volumes and blood volumes in these POTS patients. Other benefits included a reduction in orthostatic tachycardia (P < 0.01), and significantly improved quality of life as assessed by the SF-36. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: Recovery > Management of POTS and Associated Conditions > Non-Pharmacologic Strategies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p050, p062, p084. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Exercise quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Non-Pharmacological Treatment of POTS (Table 4) > Exercise Training for POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p014, p012, p019. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Exercise quote: In a number of studies, exercise has been reported to be beneficial both in alleviating POTS symptoms, as well as playing a role in curing the condition.[21] In one study, POTS patients without blood pressure fluctuations,[21] were trained gradually to move from lying to sitting to a standing position during different activities, such as swimming, rowing, and cycling. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid21690484 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21690484. Found by winnow, kev and lev in p001, p002, p024. Claude judged: supports.' - paper: pmid20579544 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20579544. Found by winnow, kev and lev in p004, p031, p033. Claude judged: supports.' - paper: pmid20309394 cited: true text: full license: by-nc-nd verdict: supports section: Results > Response to Medical therapy quote: The therapeutic management approach for these patients was based on our previous experience with the management of patients with POTS. Initial therapy consisted of an increase in salt and fluid intake as well as aerobic reconditioning with resistance training to increase lower extremity strength. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid18704621 cited: true text: full license: none verdict: supports section: Summary and what to do next quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 18704621. Found by winnow, kev and lev in p014, p018, p019. Claude judged: supports.' - paper: pmid38937334 cited: true text: full license: none verdict: partial section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid38074226 cited: true text: full license: by-nc-sa verdict: partial section: Discussion quote: The management of these patients is usually conservative as per previous literature. A regular, structured exercise programme is suggested. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Discussion quote: Gradual physical training also improves symptoms [18]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid36090156 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Although PASC and POTS might share common pathophysiological mechanisms and respond favorably to graded exercise training, few cases of PASC will likely fulfill a diagnosis of POTS. This initial case series shows the overlap between PASC, orthostatic intolerance, and POTS in recreational and competitive athletes, demonstrates the utility of performing autonomic function testing and CPET in making the diagnosis, and emphasizes the role of graded exercise training to treat this condition. note: 'Found by winnow, kev and lev in p010, p011, p014. Claude judged: partial.' - paper: pmid34327047 cited: true text: full license: by verdict: partial section: Methods > Management > Reconditioning quote: Graded-exercise training may be beneficial for symptom control in POTS.16 note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Discussion quote: Exercise to strengthen the leg muscles, such as cycling, rowing, and squatting exercises can help. note: 'Found by winnow, kev and lev in p014, p016. Claude judged: partial.' - paper: pmid32494413 cited: true text: full license: by verdict: partial section: Dr. Feigofsky examines quote: Exercise in a recumbent or semirecumbent position for 20 minutes to 30 minutes three times a week has been proven to be effective in improving orthostatic tolerance. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid28286774 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Accordingly, it seems reasonable that exercise-based rehabilitation may be effective in the medium- and long-term treatment of POTS and related conditions with deconditioning [30]. note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid19207771 cited: true text: full license: none verdict: partial section: Management > Deconditioned POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p030. Claude judged: partial.' - edge: - ivabradine_therapy - treats - pots papers: 54 evidence: - paper: pmid42605371 cited: true text: full license: by verdict: supports section: Review quote: Additional support for autoimmune or inflammatory subgroups of POTS comes from the fact that some patients experience persistent cognitive symptoms despite treatment. Common treatment options that may alter heart rate or blood pressure without eliminating autoantibodies, lessening brain inflammation, or unblocking small vessels include beta-blockers, ivabradine, and midodrine. note: 'Found by winnow, kev and lev in p019, p056. Claude judged: supports.' - paper: pmid42484150 cited: true text: full license: by verdict: supports section: Perspectivas Futuras quote: Este trabalho de revisão publicado por ABC-2025-0347 reafirma a ivabradina como uma estratégia terapêutica viável e segura para POTS, mas reforça também a necessidade de mais estudos na área. note: 'Found by winnow, kev and lev in p001, p012, p013. Claude judged: supports.' - paper: pmid42273028 cited: true text: full license: by verdict: supports section: Introduction quote: For patients with symptoms uncontrolled by conservative measures such as exercise or compression garments, clinicians must select from a wide variety of medications when treating POTS—therapies commonly prescribed for the treatment of POTS vary widely in mechanism of action and target of effects. Common pharmacologic mechanisms, with examples provided in parentheses, include mineralocorticoid agonists (fludrocortisone), medications to decrease heart rate (beta-blockers, ivabradine), vasoconstrictors (midodrine), and prescribed salt intake (11). note: 'Found by winnow, kev and lev in p003, p008, p024. Claude judged: supports.' - paper: pmid42132710 cited: true text: full license: by verdict: supports section: Discussion quote: These results provide the first direct, randomized comparative evidence that ivabradine and propranolol produce overlapping short-term hemodynamic and symptomatic improvements in POTS, with no statistically significant differences detected between active treatments. note: 'Found by winnow, kev and lev in p005, p051, p054. Claude judged: supports.' - paper: pmid41538594 cited: true text: full license: by verdict: supports section: Abstract > Conclusão quote: A ivabradina mostrou-se eficaz e segura na terapêutica dos pacientes portadores de POTS. note: 'Found by winnow, kev and lev in p005, p015, p017. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: Selective sodium channel blockers (funny current), like Ivabradine, which target the cardinal manifestation of tachycardia in POTS, have shown effectiveness in low doses in some trials [23]. note: 'Found by winnow, kev and lev in p092, p094, p095. Claude judged: supports.' - paper: pmid41364925 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41364925. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p009, p032. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Discussion quote: For ivabradine, long-term studies are also needed to further investigate potential effects in POTS. On the basis of the current evidence, ivabradine could be considered as a pharmacological approach in POTS if non-pharmacological interventions alone are not sufficient. note: 'Found by winnow, kev and lev in p046, p074, p029. Claude judged: supports.' - paper: pmid40692561 cited: true text: full license: by verdict: supports section: Methods and analysis > Analysis > Sample size justification and statistical analysis quote: The effect size (10 bpm reduction in standing heart rate) was observed along with improvement of symptoms in a prior randomized, placebo-controlled cross-over study demonstrating effectiveness of ivabradine to treat POTS (50). note: 'Found by winnow, kev and lev in p018, p041, p002. Claude judged: supports.' - paper: pmid40681233 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Discussion quote: While previous studies support the efficacy of ivabradine in treating POTS, this case reinforces it as a viable treatment option and adds real-world evidence for its inclusion in treatment guidelines. note: 'Found by winnow, kev and lev in p003, p005, p017. Claude judged: supports.' - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: For example, pacing is recommended care to manage energy levels and avoid PEM in ME/CFS; fluid/electrolytes, compression stockings and Mestinon to help manage OI; beta-blockers and ivabradine to aid tachycardia present in POTS; IgG for use in immune dysfunction; antihistamines (H1 and/or H2 inhibitors) and other select treatments to manage MCAS; low-dose naltrexone to manage pain; and melatonin to mitigate sleep problems. note: 'Found by winnow, kev and lev in p018, p033. Claude judged: supports.' - paper: pmid40624434 cited: true text: full license: by verdict: supports section: Treatment quote: Ivabradine is a selective inhibitor of I funny-channels at the sinoatrial node and may be safe and effective in patients with POTS and IST [27, 28]. note: 'Found by winnow, kev and lev in p025, p021. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Ivabradine, a sinoatrial node inhibitor, may also be a suitable treatment for patients with POTS after HSCT. It has also shown efficacy in individuals with idiopathic POTS and has been reported to reduce NE levels.27,40,41 note: 'Found by winnow, kev and lev in p037. Claude judged: supports.' - paper: pmid40294227 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40294227. Found by winnow, kev and lev in p001, p005, p011. Claude judged: supports.' - paper: pmid39882369 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). note: 'Found by winnow, kev and lev in p004, p016, p023. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Pharmacologic Therapies > Medications That Target Rapid Heart Rate quote: Ivabradine, a drug approved by the FDA for symptomatic heart failure with reduced ejection fraction, is being increasingly used in POTS patients due to its cardiac selectivity.[68] Ivabradine blocks the funny (If) current of the sinoatrial node, thereby lowering heart rate and increasing diastolic time without lowering blood pressure.[68] note: 'Found by winnow, kev and lev in p052. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Clinical management quote: Eldokla et al. (2022) reported on five patients who developed POTS after mRNA vaccination, managed with medications like ivabradine, metoprolol, fludrocortisone, and propranolol [24]. note: 'Found by winnow, kev and lev in p022, p023, p026. Claude judged: supports.' - paper: pmid39355826 cited: true text: full license: by verdict: supports section: Discussion quote: Medication use, unfortunately, is often limited by unacceptable side effects. Ivabradine, an If channel blocker, is overall tolerated better. note: 'Found by winnow, kev and lev in p015, p001. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.5. Treatments for COVID-19-Related POTS Due to Increased Norepinephrine in the Blood quote: Ivabradine is typically injected twice a day at a dose of 2.5 to 20 mg to control the heart rate of POTS patients in the recumbent position to obtain a heart rate between 50 and 70 beats per minute. This improves the symptoms of upright tachycardia in POTS patients [74]. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid39109119 cited: true text: full license: by verdict: supports section: Abstract quote: The patient’s POTS responded favorably to treatment with low-dose fludrocortisone and ivabradine. note: 'Found by winnow, kev and lev in p001, p007, p011. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Discussion quote: For example, for hyperadrenergic POTS, the sympathetic output is blocked via beta-blockers, or sympathetic symptoms such as tachycardia may be combated by pharmacotherapies such ivabradine which inhibits I(f) channels. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: Abstract quote: The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. note: 'Found by winnow, kev and lev in p001, p025. Claude judged: supports.' - paper: pmid37313107 cited: true text: full license: by verdict: supports section: Review quote: Evidence for the use of ivabradine in POTS is scant. However, it was shown to be useful in lowering heart rate and relieving symptoms. note: 'Found by winnow, kev and lev in p001, p030. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports > Pharmacological Therapies quote: Ivabradine (I-funny current; If blocker) acts selectively on the SA node to lower resting heart rates. It has been used off-label in patients with POTS and is reported to improve quality of life and reduce resting heart rates.69,70 note: 'Found by winnow, kev and lev in p035, p022, p030. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: It improves the symptoms of orthostatic tachycardia in POTS patients [78-82]. note: 'Found by winnow, kev and lev in p064. Claude judged: supports.' - paper: pmid36852364 cited: true text: full license: by verdict: supports section: Conclusions quote: We presented the case of a 15-year-old South Asian male who developed suspected POTS two weeks after receiving the Pfizer-BioNTech COVID-19 vaccine booster, which was successfully managed with low-dose fludrocortisone and ivabradine. note: 'Found by winnow, kev and lev in p004, p011, p013. Claude judged: supports.' - paper: pmid36575713 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36575713. Found by winnow, kev and lev in p008, p011, p012. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Pharmacologic Treatment > Postural Orthostatic Tachycardia Syndrome49,50,170' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p165. Claude judged: supports.' - paper: pmid35891154 cited: true text: full license: by verdict: supports section: 2. Case Presentation quote: The patient was diagnosed with POTS and started on conservative therapy with increased salt consumption, fluid intake, and 20 mmHG compression stockings. Given her persistent tachycardia, she was started on ivabradine 5 mg BID with significant improvement in her tachycardia. note: 'Found by winnow, kev and lev in p009, p014. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Management of post–COVID-19 POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Treatment > Pharmacologic interventions quote: The CCS position statement on POTS states that the most commonly used medications for the management of POTS include propranolol, midodrine, pyridostigmine, fludrocortisone, ivabradine, clonidine, methyldopa, and occasional 0.9% sodium chloride I.V. infusions.7 All are off-label for the treatment of POTS in the US. note: 'Found by winnow, kev and lev in p038, p034. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Possible Treatment for Post-COVID Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Pharmacologic management > Ivabradine quote: Ivabradine is a selective funny current blocker that does not affect blood pressure.23 Due to the selective inhibition of the sinus node, ivabradine has been used in the treatment of POTS. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid34127505 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34127505. Found by winnow, kev and lev in p001, p013, p017. Claude judged: supports.' - paper: pmid34035985 cited: true text: full license: by verdict: supports section: Discussion quote: A promising therapy that has been gaining traction recently is ivabradine, a funny sodium channel blocker (iF blocker) that has demonstrated effects including reducing the heart rate and providing symptomatic relief from POTS as well as IST without significant concomitant drops in BP.7,14,15 note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: 'Patient #1' quote: She did not tolerate beta-blockers due to worsened orthostatic intolerance, and ivabradine 7.5 mg twice a day was started (Table 2) with substantial improvement, although the patient remains on sick leave. note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid33602468 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33602468. Found by winnow, kev and lev in p004, p005. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Discussion quote: Treatment protocols for POTS have been described in detail previously.5–7 Existing protocols include increased intake rates of dietary fluids and salt, physical counter-maneuvers, and aerobic/resistance training. If these therapies are ineffective, pharmacotherapy options including fludrocortisone, midodrine, pyridostigmine, and ivabradine are trialed. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: supports.' - paper: pmid32489723 cited: true text: full license: by verdict: supports section: Introduction and background quote: However, there has been evidence of beneficial outcomes with the use of ivabradine in POTS patients, as seen in prospective and retrospective studies [12-16]. note: 'Found by winnow, kev and lev in p004, p022, p024. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Approach to therapy for patients with POTS > Pharmacologic interventions quote: Ivabradine is an alternative agent to β2 antagonists that has been shown to be of benefit in recent studies. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid29330767 cited: true text: abstract license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29330767. Found by winnow, kev and lev in p004, p003. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid29027608 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29027608. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid28846151 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28846151. Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid28496661 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28496661. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid27413567 cited: true text: full license: by verdict: supports section: 3. Case 2 quote: Then the treatment was changed to ivabradine. The patient did well during follow-up for six months without any complaints with ivabradine treatment. note: 'Found by winnow, kev and lev in p001, p011, p007. Claude judged: supports.' - paper: pmid26241226 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: Ivabradine is an effective drug for slowing the HR of POTS patients at rest and during tilting, without producing significant adverse effects. note: 'Found by winnow, kev and lev in p004, p020, p028. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid24072450 cited: true text: abstract license: none verdict: supports section: Abstract > Aims quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24072450. Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Ivabradine quote: Due to the presence of sinus tachycardia in some POTS patients, usage of a sinus node blocker, in particular, Ivabradine, was reported to improve their symptoms. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid42591853 cited: true text: full license: by verdict: partial section: ME/CFS as a low output syndrome due to small heart > Is POTS a cause of OI? quote: In the meantime, Ewan et al. (65) reported that the use of the sinus node blocker ivabradine led to dramatic improvements in both subjective and objective symptomatology, accompanied by a reduction in heart rate on standing, in a 15-year-old female patient with POTS. The use of this medication appears to improve not only tachycardia but also symptomatology, including fatigue, suggesting that tachycardia may not only be unnecessary for maintaining cerebral perfusion during standing as a compensatory mechanism but also triggers many symptoms, possibly through disturbances in the autonomic nervous system. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Pharmacologic management of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p032. Claude judged: partial.' - paper: pmid29876157 cited: true text: full license: by verdict: partial section: Review quote: The first patient's symptoms decreased without any medication. However, in the second patient, different drugs were administered, but only ivabradine had beneficial effects on the patient's symptoms [35]. note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - edge: - midodrine_therapy - treats - pots papers: 46 evidence: - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: Pharmacologic therapy, when appropriate consist of beta blockers, volume expanders, and midodrine. Ivabradine can lower sinus rate without affecting blood pressure. note: 'Found by winnow, kev and lev in p091. Claude judged: supports.' - paper: pmid42037960 cited: true text: full license: by verdict: supports section: Discussion quote: Lastly, midodrine, an α1-agonist vasoconstrictor, may be particularly useful in neuropathic POTS, where impaired vascular tone leads to excessive venous pooling [7]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: In neuropathic POTS, the loss of peripheral vascular resistance due to the sympathetic denervation, especially in the lower limbs, can be addressed with the use of vasoconstrictors like midodrine [13,24]. note: 'Found by winnow, kev and lev in p093, p095. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Conclusions quote: Pyridostigmine and midodrine might improve hemodynamics in POTS and therefore can be chosen individually as an additional therapeutic approach if non-pharmacological options alone or combined with β-adrenergic blocking agents or ivabradine are insufficient or not suitable. note: 'Found by winnow, kev and lev in p050, p053, p087. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.3. Treatment for COVID-19-Related POTS Due to Hypovolemia quote: Midodrine acts as a vasoconstrictor, reducing peripheral blood loading and improving orthostatic hypotension, and is especially recommended for the neuropathic subtype of POTS. note: 'Found by winnow, kev and lev in p024, p025. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Discussion quote: In neuropathic POTS, pharmacotherapy targets vasoconstriction with agents such as pyridostigmine and midodrine. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid37706146 cited: true text: full license: by verdict: supports section: Results quote: In addition to standard non-pharmacological management, she had previously completed trials of beta blockers, fludrocortisone, and midodrine for POTS therapy before discontinuing due to side effects. note: 'Found by winnow, kev and lev in p006, p021, p027. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: Abstract quote: The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. note: 'Found by winnow, kev and lev in p001, p025. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: '4. Individualized Pharmacologic Therapies for Pediatric POTS: Predictors of Therapeutic Efficacy' quote: Pediatric patients with POTS are often treated with non-pharmacological interventions, such as health education, exercises to improve autonomic function and sleeping therapy. The pharmacological treatment options include oral rehydration salts (ORS), midodrine hydrochloride, metoprolol, fludrocortisone and some other specialized therapies, such as droxidopa, desmopressin, erythropoietin and intravenous immunoglobulin (IVIG) [30,47,48,49,50]. note: 'Found by winnow, kev and lev in p030, p014, p020. Claude judged: supports.' - paper: pmid37313107 cited: true text: full license: by verdict: supports section: Review quote: This review found that midodrine was the most studied and effective medicine for reducing orthostatic symptoms, including dizziness and fainting. Additionally, midodrine helped patients with neuropathic and hyperadrenergic POTS by decreasing orthostatic hypotension and increasing cerebral blood flow [15]. note: 'Found by winnow, kev and lev in p004, p030, p001. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: supports section: Patient management quote: For pharmacological therapy, the society recommends midodrine (α-adrenergic agonist) and low-dose propranolol (nonselective β-blocker) for symptom relieve. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Discussion quote: Single or combination pharmacologic therapies were employed in the reported post COVID-19 cases. These include fludrocortisone, midodrine, antihistamines and ivabradine. note: 'Found by winnow, kev and lev in p015, p017, p029. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.3. Physiological Predictors for the Midodrine Hydrochloride Efficacy among POTS Children quote: An alpha-1 adrenoreceptor agonist called midodrine hydrochloride can narrow the vascular lumen through peripheral blood pressure elevation and its efficacy in the treatment of POTS has been confirmed [73]. note: 'Found by winnow, kev and lev in p027, p029, p031. Claude judged: supports.' - paper: pmid35557616 cited: true text: full license: by verdict: supports section: Results quote: Two patients received POTS-specific treatment, including fludrocortisone and midodrine, without immunomodulation. note: 'Found by winnow, kev and lev in p021, p029. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How is POTS treated? > Pharmacological treatments quote: It may be most beneficial in patients with POTS accompanied by low blood pressure.50 It is prescribed at 2.5–10 mg every 4 hours (avoiding a dose near bedtime), but it can also be used as needed for acute symptom management. note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid34733680 cited: true text: full license: by-nc-nd verdict: supports section: Case presentation quote: A 12-year-old female with POTS treated with midodrine 10 mg three times daily, presented to the emergency department (ED) following a suicide attempt. note: 'Found by winnow, kev and lev in p004, p002, p003. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Case description and results quote: PoTS alleviating medications (clonidine 675 μg/day, β-blockers such as nebivolol 5mg/day or propranolol 80mg/day or bisoprolol 2,5mg/day, etilefrinhydrochloride 10mg/day, midodrine 7,5mg/day, higher doses not tolerated) and further treatment like compression stockings, high salt and liquids diet, adapted PoTS exercise program failed to provide sufficient relief. note: 'Found by winnow, kev and lev in p015, p017. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Pharmacologic management > Midodrine and pyridostigmine quote: Midodrine is an α1-adrenergic receptor agonist that has specifically been shown to improve symptoms in dysautonomic POTS.19 note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Pharmacologic management of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: Pharmacological Treatments quote: Our center reported that midodrine hydrochloride is effective in the treatment of children with POTS through a small non-blinded randomized controlled study (38). note: 'Found by winnow, kev and lev in p017, p022, p024. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Treatment quote: Additionally, fludrocortisone19 and midodrine20,21 can be helpful in some cases, while some centers have reported good results with octreotide (an octapeptide and somatostatin analog) in patients with postprandial tachycardia; however, this medication is expensive and only available in injection form.20,22 note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Challenge II: Lack Of Standardized Approaches To Physical Rehabilitation And Psychopharmacology > Pharmacological Treatment Approaches' quote: Midodrine is an alpha-1 adrenergic agonist that has been shown to be helpful in the treatment of POTS and its effects are felt within 30–60 mins and last for 2–4 hrs.14 note: 'Found by winnow, kev and lev in p005, p018. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Approach to therapy for patients with POTS > Pharmacologic interventions quote: Fludrocortisone is a reasonable option for increasing the intravascular volume, while midodrine is useful in those with peripheral pooling. Specifically, midodrine was superior to placebo in the subgroup of patients with peripheral venous pooling (as indicated by an increase in calf diameter during venous occlusion or tilt), whereas in patients without peripheral pooling, the HR change with midodrine was not significantly different from placebo.44 note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030, p015. Claude judged: supports.' - paper: pmid27625098 cited: true text: full license: by-nc-sa verdict: supports section: THE INDIVIDUALIZED TREATMENT OF POSTURAL TACHYCARDIA SYNDROME > The alpha-adrenoreceptor agonists quote: Midodrine, an α1 adrenoreceptor agonist, can act on the α1 adrenergic receptor, constricting the vessels, so as to lessen the symptoms of POTS. note: 'Found by winnow, kev and lev in p021, p028. Claude judged: supports.' - paper: pmid26610893 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: In fact, midodrine, which is commonly used to treat symptoms associated with POTS, acts primarily by reducing venous pooling.4 note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid26241226 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: Other drugs which can also be therapeutically beneficial in patients with POTS are (1) drugs that increase peripheral vascular resistance such as midodrine, a prodrug whose active metabolite is an α-adrenoceptor antagonist, and somatostatin analogs; (2) drugs that can modify the central and peripheral activity of the sympathetic nervous system such as β-adrenoceptor antagonists (mainly propranolol), serotonin and norepinephrine uptake inhibitors, and combined α- and β-adrenoceptor antagonists; and (3) drugs that reduce the sympathetic tone such as clonidine.2,3,9 note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p041. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 4: Postural Tachycardia Syndrome and Vasovagal Syncope in the Young > Treatment of Children with Vasovagal Syncope or POTS' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p022, p063, p078. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: 'Treatment approaches: Addressing neurohormonal imbalances (Table 1) > Partial autonomic neuropathy—alpha-1 agonists' quote: More recently, it was shown that “high-flow” POTS patients were much more responsive to the treatment of midodrine than “low-flow” POTS patients (Ross et al., 2014). note: 'Found by winnow, kev and lev in p025, p026. Claude judged: supports.' - paper: pmid24857518 cited: true text: abstract license: none verdict: supports section: Abstract > Objectives quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24857518. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid24253613 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24253613. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid23978222 cited: true text: full license: none verdict: supports section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23978222. Found by winnow, kev and lev in p004, p023, p024. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid23244360 cited: true text: full license: none verdict: supports section: 'Common variant OI: POTS & postural VVS > Neuropathic POTS' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23244360. Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Vasoconstrictor Therapy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p017, p019. Claude judged: supports.' - paper: pmid21301135 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21301135. Found by winnow, kev and lev in p003, p001, p002. Claude judged: supports.' - paper: pmid20668563 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Partial dysautonomic POTS is best treated by increasing the peripheral vascular resistance and fluid volume.[10] This is often accomplished with fludrocortisones which promotes sodium and fluid retention, and midodrine which stimulates α1 -adrenergic receptors resulting in vasoconstriction. note: 'Found by winnow, kev and lev in p009, p004. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pharmacological Treatment of POTS quote: Since a failure of vascular resistance may be an integral part of neuropathic POTS, vasoconstrictors such as midodrine (an alpha-1 agonist) can be employed [40]. note: 'Found by winnow, kev and lev in p042. Claude judged: supports.' - paper: pmid10750641 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 10750641. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid40626134 cited: true text: full license: by verdict: partial section: THE CURRENT STATUS OF INDIVIDUALIZED TREATMENT OF POTS IN CHILDREN > α‐Adrenergic receptor agonists in treating children with POTS quote: Hence, patients with POTS exhibit abnormally excessive vasodilatation might benefit from α‐adrenoreceptor agonists like midodrine hydrochloride. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid38937334 cited: true text: full license: none verdict: partial section: INTRODUCTION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid34035985 cited: true text: full license: by verdict: partial section: Discussion quote: Other medications that have demonstrated success in select cases include fludrocortisone, midodrine, methylphenidate, and pyridostigmine for orthostatic syndromes.11–13 note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid32295399 cited: true text: full license: by verdict: partial section: Case quote: Fludrocortisone and midodrine were reinitiated prior to the vascular decompression surgery, and ivabradine was initiated 2 months later. Ivabradine was beneficial for the POTS symptoms and later allowed tapering of fludrocortisone and midodrine. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038. Claude judged: partial.' - paper: pmid20309394 cited: true text: full license: by-nc-nd verdict: partial section: Results > Response to Medical therapy quote: 'Pharmacotherapy was used alone or in combination in the following order: fludrocortisone 0.1mg po bid, midodrine 5-10 mg po tid, propanolol10 mg po tid, pyrodostigmine 60 mg po bid, serotonin reuptake inhibitor or modafinil 100 mg po qam. Not every patient received every medication.' note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - edge: - volume_expansion_therapy - treats - pots papers: 43 evidence: - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: Pharmacologic therapy, when appropriate consist of beta blockers, volume expanders, and midodrine. note: 'Found by winnow, kev and lev in p091, p100. Claude judged: supports.' - paper: pmid42037960 cited: true text: full license: by verdict: supports section: Discussion quote: When hypovolemia is suspected, fludrocortisone, a synthetic mineralocorticoid, is commonly used to expand plasma volume and promote sodium retention, though potential side effects include acne, headache, hypokalemia, and fluid retention. Desmopressin (DDAVP) may provide short-term symptomatic relief by promoting free water retention but carries a risk of hyponatremia. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 4 Discussion > 4.5 Rationality of current treatment approaches quote: Clinicians are advised to consider increasing salt intake or using water retention agents as a treatment strategy to improve hypovolemia and thereby alleviate POTS symptoms [12]. note: 'Found by winnow, kev and lev in p060. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Anecdotally, we found that treatment of POTS with therapies targeting sympathetic overactivity, hypovolemia, and mast cell hyperactivity has been more efficacious than neuropathic pain medications. These therapies consist of beta blockers; increased oral fluids and salt intake; intravenous fluids; and other medications, such as pyridostigmine, which enhances parasympathetic transmission; midodrine, which increases vasoconstriction and therefore improves venous return and cerebral perfusion; and benzodiazepines, which may reduce IT via GABA-mediated actions in the central autonomic networks (Table 1). note: 'Found by winnow, kev and lev in p009, p008, p012. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Pharmacologic Therapies > Medications That Target Hypovolemia quote: In addition to salt supplementation, fludrocortisone, a glucocorticoid that acts similarly to aldosterone, has shown efficacy in improving POTS symptoms.[65] note: 'Found by winnow, kev and lev in p054. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Treatment strategies and outcomes > Pharmacological treatment quote: Fludrocortisone, a mineralocorticoid that increases plasma volume, is widely used in patients with hypovolemic POTS, yielding a 25–30% improvement in orthostatic tolerance [31]. note: 'Found by winnow, kev and lev in p028, p026. Claude judged: supports.' - paper: pmid38958137 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: The medications that seemed to have the highest reported perceived efficacy by patients in combination with significant use included ondansetron (typically used for nausea), fludrocortisone (intravascular volume expansion), modafinil (fatigue), citalopram (psychiatric/autonomic modulation), and salt supplements (volume expansion). note: 'Found by winnow, kev and lev in p030, p042. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: The management of POTS relies on symptom management through intravascular volume expansion, physical exercise, and lifestyle changes as well as compressive garments. Oral fluid intake should be aimed at 3L daily with a daily salt intake of about 8-12 g of sodium chloride to help reduce hypovolemia [16]. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: supports section: Patient management quote: Given the multifactorial pathogenesis of POTS itself, several studies have compared and evaluated the efficacy of various treatment approaches, including intravascular volume expansion, vasopressor therapy, heart rate reduction, and miscellaneous therapies [38]. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports > Pharmacological Therapies quote: In addition to the aforementioned oral hydration and salt intake, pharmacological volume expansion with fludrocortisone (mineralocorticoid agonist) has been found beneficial in a number of patients. note: 'Found by winnow, kev and lev in p030, p031, p036. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: Patients are encouraged to increase fluid and salt intake, partake in aerobic exercise, and wear compression garments [2]. While there is no universal pharmacological guideline for POTS, medications such as fludrocortisone, pyridostigmine, midodrine, and beta blockers can help with its management, depending on the cause [2]. note: 'Found by winnow, kev and lev in p004, p017. Claude judged: supports.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: The main treatment for post-COVID-19 POTS is volume expansion to increase cardiac preload. Various strategies exist to achieve volume expansion in POTS patients. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid35697326 cited: true text: full license: none verdict: supports section: Nutrition Assessment and Management of Patients with POTS > Fluids and Salt quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35697326. Found by winnow, kev and lev in p009, p010, p011. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How is POTS treated? > Pharmacological treatments quote: Drugs that expand blood volume can be useful if nonpharmacologic approaches to blood volume expansion are not successful, or if low blood volume is objectively documented by an assessment of blood volume using nuclear medicine.51 Fludrocortisone (0.1–0.2 mg daily) is a synthetic version of aldosterone that promotes renal sodium absorption and secondary blood volume expansion; hypokalemia is a potential adverse effect. note: 'Found by winnow, kev and lev in p031, p038. Claude judged: supports.' - paper: pmid33926653 cited: true text: full license: none verdict: supports section: 'Abstract > Background:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33926653. Found by winnow, kev and lev in p010, p046, p001. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Available management protocols for POTS (Table 2) aim at increasing intake of fluids (water) and salt, physical countermaneuvers, and individually adapted aerobic exercise in recumbent position (1,5,9) to help correct the physiological abnormalities. Pharmacotherapy includes volume expanders, vasoconstrictors, and HR regulators but patients may remain symptomatic and incapable of work. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Management Strategies for Pots in Children and Adolescents > Pharmacological Treatment quote: Pediatric patients with POTS who are strongly suspected of having hypovolemia or inadequate salt intake are recommended to use oral rehydration salts (ORSs) for 1–3 months (5, 23, 98, 104) or to accept short-term intravenous saline as rescue treatment for patients with clinical decompensation and significant deterioration of symptoms (25). Saline supplements can alleviate symptoms in “hypovolemic” patients. note: 'Found by winnow, kev and lev in p024, p008, p023. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Hypovolemic Pots: Salt Supplements, Oral Rehydration and Fludrocortisone' quote: Hypovolemia can be seen in many POTS patients, and increasing fluids intake is an effective treatment of POTS symptoms. note: 'Found by winnow, kev and lev in p018, p021. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Treatment quote: In the common form of POTS, patients who experience a “normal adrenergic response” in the upright position may experience symptom resolution with methods such as increasing intravascular volume with intravascular saline (during acute decompensation), taking in liberal amounts of salt and water, wearing “belly button–high” compression stockings, and sleeping with the head of their bed elevated (to a 30-degree angle). Additionally, fludrocortisone19 and midodrine20,21 can be helpful in some cases, while some centers have reported good results with octreotide (an octapeptide and somatostatin analog) in patients with postprandial tachycardia; however, this medication is expensive and only available in injection form.20,22 note: 'Found by winnow, kev and lev in p010, p035, p043. Claude judged: supports.' - paper: pmid30076469 cited: true text: full license: by verdict: supports section: Treatment by comorbidity, subgrouping, and genetic profile > Treatment by comorbidity quote: Chelimsky reported that management of POTS in adolescents with CVS through fluid and salt supplementation, fludrocortisone, and low-dose propranolol reduced the numbers of vomiting episodes [6]. note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p015, p001, p003. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p029, p030. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Non-Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p034. Claude judged: supports.' - paper: pmid23999934 cited: true text: full license: none verdict: supports section: Conclusions > Potential interventions for brain fog > Non-pharmacologic interventions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23999934. Found by winnow, kev and lev in p014, p021, p023. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Volume Expansion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Sodium chloride 0.9% (Normal saline) quote: Sodium chloride 0.9% infusion has been reported very beneficial in decreasing symptoms in POTS patients and improving quality of life.[28] The infusion loads the POTS patient with sodium,[28] enhances blood and blood cell volume, and results in a slight elevation in blood pressure. note: 'Found by winnow, kev and lev in p018, p020, p019. Claude judged: supports.' - paper: pmid22561596 cited: true text: full license: none verdict: supports section: 'DISCUSSION > Blood Volume Expansion: DDAVP vs. Fludrocortisone' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22561596. Found by winnow, kev and lev in p029, p008, p023. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: supports section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Non-Pharmacological Treatment of POTS quote: Acute blood volume expansion is effective at controlling the heart rate and acutely improving symptoms. Jacob et al. [37] found that 1 liter of physiological saline infused intravenously over 1 hour decreased the orthostatic tachycardia from 33±5 bpm before the infusion to 15±3 bpm immediately following the infusion. note: 'Found by winnow, kev and lev in p039, p037. Claude judged: supports.' - paper: pmid40761644 cited: true text: full license: by verdict: partial section: Introduction quote: In the study by Ruzieh et al., though, intermittent infusions of saline dramatically reduced symptoms and improved quality of life in patients suffering from refractory POTS (21). note: 'Found by winnow, kev and lev in p003, p006, p008. Claude judged: partial.' - paper: pmid38240001 cited: true text: full license: by verdict: partial section: METHODS > Treatment options quote: As a standard treatment for POTS, patients were counseled to consume ≥10 g of salt and 2–3 L of water, except for those with hypertension and older people; instructed to wear elastic compression stockings up to the thighs; and prescribed bisoprolol, a β1‐selective blocker, once daily. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Management: Lifestyle Changes > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p118. Claude judged: partial.' - paper: pmid35870963 cited: true text: full license: by verdict: partial section: Results > Patient 2 quote: Treatment of orthostatic intolerance consisted of increased dietary intake of fluids and sodium chloride, as well as buffered sodium chloride tablets (2712 mg daily). note: 'Found by winnow, kev and lev in p027, p023, p031. Claude judged: partial.' - paper: pmid35742222 cited: true text: full license: by verdict: partial section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.2. Physiological Predictors for the Oral Rehydration Salts Efficacy in Pediatric POTS quote: Therefore, in patients with POTS, an intravenous saline or oral rehydration solution (ORS) could prevent syncope and improve OI and result in changes in the HR. However, the efficacy of salt replenishment was observed only in some POTS patients [61,62]; therefore, a worthwhile research topic would be a method for identifying responders to this therapy. note: 'Found by winnow, kev and lev in p016, p020. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Treatment > Nonpharmacologic interventions quote: Two to three liters of water and 10 to 12 g of sodium daily is recommended by the HRS for patients with POTS and can be accomplished through diet or supplemental sodium tablets.5,7,23 note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - paper: pmid34327047 cited: true text: full license: by verdict: partial section: Methods > Pharmacologic management > Fludrocortisone and desmopressin quote: For hypovolemic POTS, fludrocortisone and desmopressin may help with symptom control. note: 'Found by winnow, kev and lev in p013, p015. Claude judged: partial.' - paper: pmid33262898 cited: true text: full license: by verdict: partial section: Discussion quote: Existing protocols include increased intake rates of dietary fluids and salt, physical counter-maneuvers, and aerobic/resistance training. If these therapies are ineffective, pharmacotherapy options including fludrocortisone, midodrine, pyridostigmine, and ivabradine are trialed. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Discussion quote: Fluid intake up to 2.5 liters daily, which is equivalent to 10 standard cups a day and a total of 10 grams of sodium chloride daily, noting that one salt tablet contains one gram of sodium chloride, helps expand the plasma volume and improve venous return and the re-loading of the right atrium. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid31405524 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31405524. Found by winnow, kev and lev in p009, p004, p030. Claude judged: partial.' - paper: pmid25980576 cited: true text: full license: none verdict: partial section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p022, p023. Claude judged: partial.' - paper: pmid24982638 cited: true text: full license: by verdict: partial section: 'Treatment approaches: Addressing neurohormonal imbalances (Table 1) > Hypovolemia and renin-angiotensin-aldosterone paradox—volume loading' quote: The use of volume loading with intravenous saline is effective at acutely relieving the symptoms of POTS. note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid23753844 cited: true text: full license: none verdict: partial section: Non-Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p031. Claude judged: partial.' - paper: pmid20309394 cited: true text: full license: by-nc-nd verdict: partial section: Results > Response to Medical therapy quote: The therapeutic management approach for these patients was based on our previous experience with the management of patients with POTS. Initial therapy consisted of an increase in salt and fluid intake as well as aerobic reconditioning with resistance training to increase lower extremity strength. note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - edge: - lifestyle_modification - treats - pots papers: 37 evidence: - paper: pmid35697326 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35697326. Found by winnow, kev and lev in p004, p008, p010. Claude judged: supports.' - paper: pmid42299168 cited: true text: full license: by verdict: partial section: Review quote: Other environmental triggers, such as extreme heat and dehydration, aggravate symptoms of POTS [5]. Early counseling is recommended to avoid such conditions by proactively hydrating and increasing sodium intake. note: 'Found by winnow, kev and lev in p053, p091, p100. Claude judged: partial.' - paper: pmid41301791 cited: true text: full license: by verdict: partial section: 4. Neurologic Evaluation > 4.5. Treatment quote: Finally, aside from a high-sodium diet, gluten-free low-carb diet may be beneficial in some patients with POTS [34]. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid41142154 cited: true text: full license: by verdict: partial section: Discussion quote: Dietary management is another key area, as POTS symptoms often respond to changes in salt intake and hydration (4). note: 'Found by winnow, kev and lev in p032. Claude judged: partial.' - paper: pmid40869705 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Additional recommendations include a high-salt diet (6–10 g/day) and increased fluid intake (2.5–3 L/day); using compression garments (covering large venous reservoirs in the lower limbs and the pelvic region); consuming small, low-carbohydrate meals; avoiding prolonged bed rest; performing counter-maneuvers to prevent syncope (e.g., leg crossing and muscle tensing); avoiding caffeine, alcohol, and excessive heat; and strengthening psychological and social support [6]. note: 'Found by winnow, kev and lev in p002, p023. Claude judged: partial.' - paper: pmid40624434 cited: true text: full license: by verdict: partial section: Treatment quote: Avoiding dehydration, prolonged sitting or standing, and medications that can exacerbate orthostatic symptoms is advised. note: 'Found by winnow, kev and lev in p009, p020. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Treatments and Therapies > Non-pharmacologic Therapies quote: Dietary changes can significantly improve the quality of life of POTS patients. note: 'Found by winnow, kev and lev in p047, p045. Claude judged: partial.' - paper: pmid39552985 cited: true text: full license: by verdict: partial section: Abstract quote: The patient made a remarkable functional recovery from POTS, as she responded well to pharmacotherapy, primarily beta-blockers, along with lifestyle modifications. note: 'Found by winnow, kev and lev in p001, p009, p025. Claude judged: partial.' - paper: pmid39355826 cited: true text: full license: by verdict: partial section: Case report quote: She was discharged from the hospital with the advice to continue with increased fluid and dietary salt intake as well as aerobic exercise as tolerated. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 4. Management > 4.1. Patient Education quote: An important aspect of COVID-19-related POTS management is patient education. Avoiding lying down, overeating, and high temperatures and humidity, and obtaining sufficient sleep should be primarily considered. note: 'Found by winnow, kev and lev in p022, p024. Claude judged: partial.' - paper: pmid39109119 cited: true text: full license: by verdict: partial section: Discussion quote: Patient education is a cornerstone of treatment, empowering individuals to understand and manage their symptoms. In addition, POTS patients are encouraged to avoid exacerbating factors such as dehydration and extreme heat exposure [21]. note: 'Found by winnow, kev and lev in p007, p011. Claude judged: partial.' - paper: pmid38962840 cited: true text: full license: by-nc-nd verdict: partial section: INTRODUCTION quote: POTS is mainly treated symptomatically with behavior modification, increased fluid and salt intake, compression garments, and off‐label medications. note: 'Found by winnow, kev and lev in p010, p004, p011. Claude judged: partial.' - paper: pmid38958137 cited: true text: full license: by-nc-nd verdict: partial section: RESULTS quote: Overall, the various types of interventions for POTS shown to be most helpful included the addition of medication(s), increased fluid and salt intake, and increased exercise (Table 7). Nearly 90% of patients continued to require increased salt and water intake as well as exercise to manage their POTS symptoms, with a median fluid intake of 64 ounces per day (IQR 48–96). note: 'Found by winnow, kev and lev in p030, p043, p044. Claude judged: partial.' - paper: pmid38074226 cited: true text: full license: by-nc-sa verdict: partial section: Discussion quote: The patient should be advised on standing slowly and carefully from a lying or seated position and avoiding exacerbating factors such as alcohol intake, caffeine, prolonged standing and dehydration. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 7. Treatment quote: It is advisable to avoid situations that can exacerbate symptoms, which has also been shown to be beneficial in POTS after SARS-CoV-2 infection (Table 1) (17, 87, 88). note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - paper: pmid37519618 cited: true text: full license: by verdict: partial section: Discussion quote: Patient education is a crucial component of managing POTS cases. For the prevention of severe symptoms, the patient should be advised to avoid extremes of temperature, do strenuous exercise in upright posture in the initial phases, and be vigilant immediately in the post-prandial period after eating. note: 'Found by winnow, kev and lev in p020. Claude judged: partial.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: Patient management quote: Treatment for these patients is aimed at alleviating symptoms, improving blood volume, and lifestyle changes. note: 'Found by winnow, kev and lev in p027. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports quote: Majority of patients showed quite a marked improvement in symptoms with lifestyle measures, beta blockers, fludrocortisone and occasional ivabradine use. note: 'Found by winnow, kev and lev in p022, p030. Claude judged: partial.' - paper: pmid36938206 cited: true text: full license: by verdict: partial section: Discussion quote: Behavioral changes to reduce triggers and maintenance of an upright posture to avoid deconditioning are recommended [12]. note: 'Found by winnow, kev and lev in p004, p017. Claude judged: partial.' - paper: pmid36339677 cited: true text: full license: by verdict: partial section: Results > POTS management quote: Other non-pharmacological interventions include increased fluid and salt intake, physical counter maneuvers (muscle contraction, leg crossing)33, compression devices, avoidance of medication worsening POTS, and avoidance of POTS symptom exacerbation such as caffeine and alcohol intake and heat exposure21,24,34. note: 'Found by winnow, kev and lev in p014, p017, p029. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Management: Lifestyle Changes > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p123, p118, p124. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Treatment > Nonpharmacologic interventions quote: It is important that the patient start a graduated exercise plan, beginning with recumbent exercises, and take caution not to overexert.14 The patient should avoid activities that may cause overheating. note: 'Found by winnow, kev and lev in p029, p030. Claude judged: partial.' - paper: pmid34792683 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34792683. Found by winnow, kev and lev in p006, p003. Claude judged: partial.' - paper: pmid34786979 cited: true text: full license: by verdict: partial section: Results and discussion > Adapting to cope with PoTS quote: Dietary changes such as increasing sodium intake,33 reducing refined carbohydrates and foods high in fat and fibre are often recommended in this population who are more likely to struggle with delayed gastric emptying.34 note: 'Found by winnow, kev and lev in p049. Claude judged: partial.' - paper: pmid33689063 cited: true text: full license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33689063. Found by winnow, kev and lev in p004, p001, p007. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Discussion quote: The management of our POTS patients included education and reassurance, non-pharmacological measures, and drugs, as no single therapy is effective. In our experience, most patients responded to counselling, regarding the essentiality of doing recumbent exercises, avoid long-standing and overheating, drink an excess of water, excess intake of salt, elevate the head end of the bed, elastic compression and beta-blocker therapy. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid33262898 cited: true text: full license: by verdict: partial section: Discussion quote: Treatment protocols for POTS have been described in detail previously.5–7 Existing protocols include increased intake rates of dietary fluids and salt, physical counter-maneuvers, and aerobic/resistance training. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: partial.' - paper: pmid32494413 cited: true text: full license: by verdict: partial section: Ms. Lei, Ms. Sheikh, and Dr. Raj consider quote: Lasting improvements in POTS symptoms rely on therapy regimens founded upon lifestyle changes that begin with the maintenance of high fluid and dietary salt intake, with the primary goal of augmenting plasma volume. note: 'Found by winnow, kev and lev in p023, p035, p010. Claude judged: partial.' - paper: pmid29628432 cited: true text: full license: none verdict: partial section: 5. Treatment Strategies for Cognitive Dysfunction in POTS > 5.2 Non-Pharmacological interventions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29628432. Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid29549458 cited: true text: full license: none verdict: partial section: Results > Postural Tachycardia Syndrome, Gastrointestinal Symptoms and Splanchnic Circulation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: partial section: Approach to therapy for patients with POTS quote: The first consideration in managing POTS is patient education concerning pathophysiology and symptoms, with numerous simple lifestyle strategies aimed to reduce the burden of POTS-related symptoms. note: 'Found by winnow, kev and lev in p022, p021, p023. Claude judged: partial.' - paper: pmid28674681 cited: true text: full license: by verdict: partial section: Co-morbid Conditions > Orthostatic Intolerance (OI) > Management/Treatment > Avoid Pooling of Blood quote: This involves avoiding prolonged standing or sitting, such as by moving around during longer classroom lectures, standing and stretching periodically to break up study sessions, and shopping at off hours. Patients should avoid saunas, hot-tubs and sunbathing, and take short, cool baths, and showers. note: 'Found by winnow, kev and lev in p170. Claude judged: partial.' - paper: pmid23999934 cited: true text: full license: none verdict: partial section: Conclusions > Potential interventions for brain fog > Non-pharmacologic interventions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23999934. Found by winnow, kev and lev in p013, p021. Claude judged: partial.' - paper: pmid23753844 cited: true text: full license: none verdict: partial section: Non-Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: partial section: Treatment > Diet quote: Changing diet and eating habits and increasing fluid intake help people with POTS. Eating small meals has been said to reduce the severity of postprandial hypotension, because the amount of blood required for digestion is reduced.[24] note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid21977261 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p012, p018. Claude judged: partial.' - paper: pmid16943900 cited: true text: full license: by verdict: partial section: Non-Pharmacological Treatment of POTS quote: It is important to educate the patient about the nature of the disorder. The patient should avoid aggravating factors such as dehydration, and extreme heat. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - edge: - compression_therapy - treats - pots papers: 30 evidence: - paper: pmid42299168 cited: true text: full license: by verdict: supports section: Review quote: Based on history and physical examination findings, the patient is diagnosed with POTS. She is recommended to increase fluid and salt intake, use compression garments, and start a structured recumbent exercise program. note: 'Found by winnow, kev and lev in p091, p100. Claude judged: supports.' - paper: pmid41976810 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Conservative treatment includes aiming for 2–3 L of fluids a day and 10–12 g of salt a day, using compression garments, and techniques such as squeezing the buttocks and crossing the legs when standing [3,4,5]. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid41898333 cited: true text: full license: by verdict: supports section: 12. Discussion quote: The evidence for this mechanism comes from improved orthostatic symptoms in patients with POTS following compression garment therapy [29,111], symptomatic improvement following interventions that augment venous return [113], and experimental evidence demonstrating increased autonomic signaling with occlusion of veins [102,103]. note: 'Found by winnow, kev and lev in p031, p037. Claude judged: supports.' - paper: pmid41483109 cited: true text: full license: none verdict: supports section: Discussion > Physiological Efficacy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41483109. Found by winnow, kev and lev in p008, p057. Claude judged: supports.' - paper: pmid41338488 cited: true text: full license: by verdict: supports section: Body quote: Compression garments are a frequently prescribed treatment for POTS. Compression garments provide pressure to the abdomen and legs, shifting pooled blood back to the heart. note: 'Found by winnow, kev and lev in p004, p007, p008. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Results > Non-pharmacological interventions quote: In total, seven RCT and 13 non-RCTs assessing non-pharmacological therapeutic options in POTS were analysed. Interventions include breathing devices, compression garments, physical exercise, salt supplementation, transdermal vagus nerve stimulation (tVNS), increased oral water intake, intravenous saline infusions and gluten-free diet. note: 'Found by winnow, kev and lev in p015, p017, p018. Claude judged: supports.' - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Results > Treatments Impact Core Disease Symptoms Differently. quote: As expected, compression stockings and Mestinon most frequently improved symptoms of POTS (63.7% and 56.9%, respectively), while beta blockers and ivabradine primarily alleviated POTS symptoms (66.0%). note: 'Found by winnow, kev and lev in p018, p033. Claude judged: supports.' - paper: pmid40475217 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: Abdominal compression bands may relieve symptoms while standing and improve hemodynamic and autonomic nervous functions in children with POTS. note: 'Found by winnow, kev and lev in p004, p008, p032. Claude judged: supports.' - paper: pmid39685762 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Compression garments are known to reduce symptoms in POTS and nOH [17,18,19,20]. Patients with POTS and nOH typically have excessive venous pooling in the legs and abdomen due to inadequate vascular tone [21]. note: 'Found by winnow, kev and lev in p004, p005, p001. Claude judged: supports.' - paper: pmid39614865 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39614865. Found by winnow, kev and lev in p004, p005, p001. Claude judged: supports.' - paper: pmid39582711 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Although compression garments are commonly used as a treatment for patients with POTS, little is known about the patient experience with these garments. note: 'Found by winnow, kev and lev in p006, p015, p052. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Non-pharmacological treatment quote: Non-pharmacological interventions are crucial in managing POTS and can significantly improve patient outcomes. Key strategies include increased fluid and salt intake, physical counter-maneuvers, exercise training, and the use of compression garments [37]. note: 'Found by winnow, kev and lev in p022, p028, p030. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.4. Treatment for COVID-19-Related POTS Due to Intravenous or Splanchnic Pooling quote: For non-pharmacological intervention, compression stockings of 30 to 40 mmHg can be used as well as abdominal binders of 10 mmHg in POTS [52]. Abdominal binders are more useful than compression stockings because significant amounts of venous blood are shifted from visceral veins via abdominal compression [68,69]. note: 'Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid38260095 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Abdominal and lower-extremity compression garments have been used as a potential treatment for POTS (Heyer, 2014; Bryarly et al., 2019; Bourne et al., 2021). note: 'Found by winnow, kev and lev in p005, p004, p029. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: supports section: Patient management quote: Given the multifactorial pathogenesis of POTS itself, several studies have compared and evaluated the efficacy of various treatment approaches, including intravascular volume expansion, vasopressor therapy, heart rate reduction, and miscellaneous therapies [38]. Based on current evidence, the Canadian Cardiovascular Society recommends non-pharmacological therapy as the first line management approach – withdrawal of exacerbating medications, increasing blood volume with dietary interventions, use of compression stockings, adoption of head-up tilt sleeping position, and semi-recumbent exercises [39]. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: Compressive garments significantly reduce venous pooling and improve POTS symptoms [73]. note: 'Found by winnow, kev and lev in p059. Claude judged: supports.' - paper: pmid36694653 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: "Compression garments have been highlighted as a tool in the management of PoTS,\n23\n, \n24\n therefore\ \ the compressive effects of DEFOs might help to reduce symptoms." note: 'Found by winnow, kev and lev in p005, p015. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Lifestyle Changes > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p119, p128. Claude judged: supports.' - paper: pmid34390682 cited: true text: full license: none verdict: supports section: Possible Treatment for Post-COVID Tachycardia Syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34390682. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid33478652 cited: true text: abstract license: none verdict: supports section: Abstract > Objectives quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33478652. Found by winnow, kev and lev in p002, p004, p005. Claude judged: supports.' - paper: pmid32673517 cited: true text: full license: by-nc verdict: supports section: Body quote: Thus, compression of venous capacitance beds in the abdomen or lower body with compression garments has been widely recommended as a nonpharmacologic approach for the treatment of POTS, alone and in combination with drug therapy, to attenuate orthostatic venous pooling,1, 4, 14, 15, 16, 17 particularly in the splanchnic capacitance bed where excessive pooling has been reported in some POTS patients.18, 19 note: 'Found by winnow, kev and lev in p012, p001, p013. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Treatment quote: In the common form of POTS, patients who experience a “normal adrenergic response” in the upright position may experience symptom resolution with methods such as increasing intravascular volume with intravascular saline (during acute decompensation), taking in liberal amounts of salt and water, wearing “belly button–high” compression stockings, and sleeping with the head of their bed elevated (to a 30-degree angle). note: 'Found by winnow, kev and lev in p010, p048. Claude judged: supports.' - paper: pmid31788462 cited: true text: full license: by verdict: supports section: Discussion quote: Based on current understanding of potential etiology, several non-pharmacological treatments have been introduced into POTS treatment, such as reducing venous pooling by wearing lower-body compression garments or practicing resistance training for the thighs (23). note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: 4. REDUCTION IN VENOUS POOLING quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p019, p020, p001. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Approach to therapy for patients with POTS > Nonpharmacologic interventions quote: The use of full-length pressure stockings can be of considerable benefit in reducing POTS symptoms. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Non-Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid24840763 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24840763. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Non-Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p042, p030. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Non-Pharmacological Treatment of POTS quote: Elastic support hose can help to minimize the degree of peripheral venous pooling and enhance venous return. We recommend 30-40 mmHg of counter-pressure and they should come up to the waist. note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038. Claude judged: partial.' - edge: - pyridostigmine_therapy - treats - pots papers: 27 evidence: - paper: pmid41684377 cited: true text: full license: by-nc verdict: supports section: Case presentation quote: Due to persistent symptoms, pyridostigmine was added at 30 mg BID and titrated to 60 mg TID as a treatment of POTS, which resulted in significant symptomatic improvement. note: 'Found by winnow, kev and lev in p002, p004, p005. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Discussion quote: Evidence is still scarce and no studies on its use in children were found, so further studies on the long-term use of pyridostigmine in children and adults are essential to assess its effects on POTS. However, pyridostigmine could be considered as a potential treatment option in POTS if non-pharmacological interventions and the use of β-adrenergic blocking agents or ivabradine are not sufficient. note: 'Found by winnow, kev and lev in p040, p029, p074. Claude judged: supports.' - paper: pmid40681233 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Short-term use of desmopressin may be considered for patients who are hypovolemic, whereas pyridostigmine has been proven to provide long-term improvement in patients.4 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Anecdotally, we found that treatment of POTS with therapies targeting sympathetic overactivity, hypovolemia, and mast cell hyperactivity has been more efficacious than neuropathic pain medications. These therapies consist of beta blockers; increased oral fluids and salt intake; intravenous fluids; and other medications, such as pyridostigmine, which enhances parasympathetic transmission; midodrine, which increases vasoconstriction and therefore improves venous return and cerebral perfusion; and benzodiazepines, which may reduce IT via GABA-mediated actions in the central autonomic networks (Table 1). note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.6. Treatment for COVID-19-Related POTS Due to an Autoimmune Mechanism quote: Pyridostigmine is typically administered in dosages ranging from 30 to 60 mg, three times daily. The drug helps reduce heart rate increase upon standing and alleviates the clinical symptoms of orthostatic intolerance in patients with POTS [76]. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid37313107 cited: true text: full license: by verdict: supports section: Review quote: Although pyridostigmine was proven to alleviate symptoms, insufficient data supports its usage in children and adolescents. note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Review of Clinical Reports > Pharmacological Therapies quote: Pyridostigmine (an acetylcholinesterase inhibitor) has been used with some benefit, particularly in patients with autoimmune / paraneoplastic POTS. note: 'Found by winnow, kev and lev in p035, p030. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Pyridostigmine: It’s a reversible acetylcholinesterase inhibitor usually given in a dose of 30 to 60 mg three times per day. It improves orthostatic heart rate and clinical symptoms of orthostatic intolerance in POTS patients [87].' note: 'Found by winnow, kev and lev in p067. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Pharmacologic Treatment > Postural Orthostatic Tachycardia Syndrome49,50,170' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p163. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: How is POTS treated? > Pharmacological treatments quote: A 2005 study found that pyridostigmine (30–60 mg, given orally 3 times daily) can acutely decrease upright heart rate in patients with POTS;48 it acts either by directly increasing vagal tone or by increasing sympathetic vasoconstriction. note: 'Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Pharmacologic management > Midodrine and pyridostigmine quote: In a small, placebo-controlled crossover study of 17 patients with POTS, the orthostatic heart rate was significantly improved at two and four hours after the administration of 30 mg of pyridostigmine relative to placebo therapy.20 Study participants reported a significant improvement in symptom burden on pyridostigmine after four hours without an observed effect on blood pressure, demonstrating that proper vascular tone in these patients plays a significant role in dysautonomic POTS.20 note: 'Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Medicações como midodrina associadas a baixa dose de betabloqueador não seletivo (propranolol), fludrocortisona e piridostigmina são úteis nas formas disautonômicas e hipovolêmicas da SPOT. note: 'Found by winnow, kev and lev in p133. Claude judged: supports.' - paper: pmid33423527 cited: true text: full license: by-nc-nd verdict: supports section: Results > Hemodynamics Before and During the Modified Oxford Method > SAP Presodium Nitroprusside quote: In contrast, SAP was reduced when supine in POTS unmedicated, increasing with the addition of pyridostigmine or digoxin to control levels while remaining supine. With tilt, SAP was reduced in all POTS compared with control regardless of treatment. note: 'Found by winnow, kev and lev in p028, p044, p031. Claude judged: supports.' - paper: pmid33244220 cited: true text: full license: by-nc verdict: supports section: Patients and Methods > Medications Associated with DES quote: Furthermore, patients with POTS are commonly prescribed pyridostigmine for autonomic symptom management. note: 'Found by winnow, kev and lev in p016, p031. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: 'Treatment of Neuropathic Pots: Midodrine and Pyridostigmine' quote: Pyridostigmine, a peripheral acetylcholinesterase inhibitor, could be used to treat patients with POTS. note: 'Found by winnow, kev and lev in p026, p017. Claude judged: supports.' - paper: pmid31788462 cited: true text: full license: by verdict: supports section: Introduction quote: Currently used drugs for POTS include β-adrenoreceptor blockers, α-adrenoreceptor agonists, pyridostigmine and fludrocortisone, each of which has a distinct while overlapping mechanism underlying its observed clinical efficacy (3). note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid29102451 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Treatment of POTS (Table 2) > Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p040. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid24982638 cited: true text: full license: by verdict: supports section: 'Treatment approaches: Addressing neurohormonal imbalances (Table 1) > Hyperadrenergic state—heart rate control' quote: Pyridostigmine, an acetylcholinesterase inhibitor, has also been used to manage orthostatic tachycardia (Raj, 2013). note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: Recovery > Management of POTS and Associated Conditions > Medications for Blood Flow quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p092. Claude judged: supports.' - paper: pmid23244360 cited: true text: full license: none verdict: supports section: 'Common variant OI: POTS & postural VVS > Neuropathic POTS' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23244360. Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Increasing Vagal Tone quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid22783324 cited: true text: full license: by-nc-sa verdict: supports section: Treatment > Pyridostigmine bromide quote: Occasionally pyridostigmine bromide is used to treat POTS.[41],[42] Pyridostigmine bromide enhances the effect of acetylcholine by inhibiting its breakdown,[43] but some studies suggest that the pathophysiology in some POTS atients is related to the production of antibodies that block the acetylcholine receptor. note: 'Found by winnow, kev and lev in p025, p026. Claude judged: supports.' - paper: pmid21410722 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21410722. Found by winnow, kev and lev in p002, p001, p003. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pharmacological Treatment of POTS quote: By increasing the levels of synaptic acetylcholine at both the autonomic ganglia and the peripheral muscarinic parasympathetic receptors, pyridostigmine significantly restrained the heart rate in response to standing in our patients with POTS. We prescribe pyridostigmine 30mg to 60 mg PO TID alone or in combination with low dose propranolol. note: 'Found by winnow, kev and lev in p043. Claude judged: supports.' - paper: pmid15911704 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15911704. Found by winnow, kev and lev in p002, p003. Claude judged: supports.' - edge: - central_sympatholytic_therapy - treats - pots papers: 17 evidence: - paper: pmid40681233 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Central sympatholytic agents such as methyldopa or clonidine may also be used, and if these are not tolerated, peripheral β-adrenergic therapies are considered.4 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Pharmacologic Therapies > Medications That Target Sympathetic Activity quote: Clonidine, an α2-adrenergic receptor agonist, improves POTS symptoms by decreasing sympathetic activity and reducing autonomic instability.[9] Methyldopa, a longer acting α2-adrenergic receptor agonist, is reported to be better tolerated by POTS patients than clonidine.[74] note: 'Found by winnow, kev and lev in p055. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 4. Management > 4.5. Treatments for COVID-19-Related POTS Due to Increased Norepinephrine in the Blood quote: Clonidine and methyldopa may be effective for POTS by decreasing central sympathetic signals [75]. note: 'Found by winnow, kev and lev in p026. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p035, p003, p004. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Pharmacologic Treatment > Postural Orthostatic Tachycardia Syndrome49,50,170' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p166. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Na forma hiperadrenérgica, a clonidina ou alfa-metildopa podem ser eficazes (classe IIb).11 note: 'Found by winnow, kev and lev in p133, p166. Claude judged: supports.' - paper: pmid32805514 cited: true text: full license: none verdict: supports section: ETIOLOGY AND PREDISPOSING CONDITIONS > Neurogenic Orthostatic Hypotension > Exacerbating Medications quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32805514. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Treatment > Pharmacologic treatment' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pharmacological Treatment of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p039. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Pharmacological Treatment of POTS (Table 6) > Vanderbilt Approach to Pharmacotherapy for POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p016, p019. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pharmacological Treatment of POTS quote: Central sympatholytic medications are often useful and well tolerated in patients with the central hyperadrenergic form of POTS, but may not be as well tolerated in neuropathic POTS. note: 'Found by winnow, kev and lev in p040, p029. Claude judged: supports.' - paper: pmid42696970 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42696970. Found by winnow, kev and lev in p001, p004, p002. Claude judged: partial.' - paper: pmid41446482 cited: true text: full license: by verdict: partial section: Discussion quote: Central sympatholytic drugs like clonidine and methyldopa have been shown to positively impact the symptoms in the hyperadrenergic variant of POTS but remain of limited use in the neuropathic variant [2]. note: 'Found by winnow, kev and lev in p091. Claude judged: partial.' - paper: pmid40951270 cited: true text: full license: by verdict: partial section: Discussion quote: The central sympatholytic drug, e.g., guanfacine, has been shown to improve symptoms in hyperadrenergic POTS[8]. note: 'Found by winnow, kev and lev in p042. Claude judged: partial.' - paper: pmid29102451 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome > Pharmacological Treatment quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29102451. Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038. Claude judged: partial.' - paper: pmid19207771 cited: true text: full license: none verdict: partial section: Management > Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p029. Claude judged: partial.' - edge: - immunomodulatory_therapy - treats - pots papers: 17 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Immunotherapies > Immunologic therapies and ongoing clinical trials for POTS and other common autonomic disorders > Other traditional immunomodulators quote: Although immunomodulating therapies have not been typically included in the standard pharmacologic approaches for POTS and OCADs, these treatment options have been gaining utility, especially in the context of comorbid UCTD, systemic autoimmune disorders, and Long COVID. These pharmacotherapies include oral, IV, and subcutaneous (SQ) corticosteroids, low-dose naltrexone, and immunosuppressants, such as hydroxychloroquine. note: 'Found by winnow, kev and lev in p022, p025, p029. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Treatments and Therapies > Pharmacologic Therapies > Medications with Undefined Mechanisms or Subtype-specific Targets quote: For patients with autoimmune-associated POTS, particularly those diagnosed with SFN, IVIG and plasmapheresis have demonstrated improvement in symptoms.[79] note: 'Found by winnow, kev and lev in p028, p058. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Treatment strategies and outcomes > Pharmacological treatment quote: IVIG has emerged as a potential treatment option in immune-mediated POTS cases, showing a 50% improvement in HRV in some patients after six months of therapy [28]. note: 'Found by winnow, kev and lev in p024, p023, p025. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.6. Treatment quote: Kesterson et al. presented a case series of seven patients with POTS treated with subcutaneous immunoglobulin or plasmapheresis. note: 'Found by winnow, kev and lev in p037, p034, p036. Claude judged: supports.' - paper: pmid36008726 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36008726. Found by winnow, kev and lev in p001, p004, p003. Claude judged: supports.' - paper: pmid35557616 cited: true text: full license: by verdict: supports section: Abstract > Objectives quote: We observed postural orthostatic tachycardia syndrome (POTS) which resolved with immunomodulation in a patient with Pediatric acute-onset neuropsychiatric syndrome (PANS). note: 'Found by winnow, kev and lev in p001, p021. Claude judged: supports.' - paper: pmid34471867 cited: true text: full license: by verdict: supports section: Abstract > Conclusions quote: These findings suggest that autoimmune-mediated neuropathic PoTS can be treated sufficiently with IVIg whereas SCIg minimizes side-effects. note: 'Found by winnow, kev and lev in p005, p017, p004. Claude judged: supports.' - paper: pmid34117922 cited: true text: full license: by verdict: supports section: Immunomodulatory treatment in postural tachycardia syndrome > Comment quote: This case series describes improvement in subjective and objective measures of orthostatic intolerance in six patients with positive autoantibodies treated with six cycles of IVIG. The open label nature of the case series creates ample opportunity for reporting bias but is a promising result for the use of IVIG in patients with refractory POTS with suspected autoimmunity. note: 'Found by winnow, kev and lev in p016, p017, p014. Claude judged: supports.' - paper: pmid33677650 cited: true text: full license: none verdict: supports section: CNS-targeted therapy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid33382525 cited: true text: abstract license: none verdict: supports section: Abstract > Background And Purpose quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33382525. Found by winnow, kev and lev in p004, p001, p002. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Abstract quote: IVIg is emerging as a promising therapy for POTS. note: 'Found by winnow, kev and lev in p001, p011, p014. Claude judged: supports.' - paper: pmid41403551 cited: true text: full license: by-nc-sa verdict: partial section: Case Report quote: Self-measurements of blood pressure before, during, and after the three IVIG cycles showed an overall reduction in the difference between systolic blood pressure values and heart rate in the supine position compared to the upright position [Figure 1]. The tilt table tests before and after the IVIGs also showed a significant reduction in the difference in blood pressure between the supine and upright positions [Table 2]. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid40624434 cited: true text: full license: by verdict: partial section: Treatment quote: Finally, immunotherapy is emerging as potentially effective in severe, treatment-refractory patients with POTS, post-COVID dysautonomia and other forms of dysautonomia and is considered standard therapy for autonomic disorders such as autoimmune autonomic ganglionopathy (AAG) and autoimmune autonomic neuropathies (AAN) in general [36–38]. note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: partial section: Discussion quote: While IVIG is still under investigation, two of three patients in this case series noted relative improvement in symptoms shortly after its administration. Importantly, all three patients tolerated the IVIG treatment without complication. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid33505857 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Although the exact mechanism behind the treatment’s efficaciousness must be further studied, we present one of the first recorded alleviations of POTS using immunomodulatory therapy. note: 'Found by winnow, kev and lev in p007, p009. Claude judged: partial.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: partial section: Discussion > Immunomodulatory Treatments in Patients With POTS quote: Taken together, these above reports on efficacy of immunomodulatory therapy in select patients with POTS lack both systematic assessment of serum positivity for autoantibodies against GPCRs as entrance criterion and randomization of patients to a placebo‐controlled arm. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid31547756 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: The use of immunotherapy in POTS is currently controversial, although case reports and case series have shown that immune therapy improves POTS symptoms in patients with comorbid autoimmune diseases and refractory disease.3, 15, 16 note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - physical_countermaneuvers - treats - pots papers: 12 evidence: - paper: pmid41976810 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Conservative treatment includes aiming for 2–3 L of fluids a day and 10–12 g of salt a day, using compression garments, and techniques such as squeezing the buttocks and crossing the legs when standing [3,4,5]. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Non-pharmacological treatment quote: Exercise and physical counter-maneuvers, such as muscle contraction and leg crossing, are essential for promoting venous return and maintaining hemodynamic stability. The incorporation of these non-pharmacological strategies into daily routines has been associated with a 40% reduction in HRV and a significant decrease in orthostatic symptoms, making them a cornerstone of POTS management [42]. note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Management: Lifestyle Changes > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p123. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.1. Physiological Indicators Predicting the Efficacy of Non-Pharmacotherapy Treatment in Children with POTS quote: These treatments include physical movement, exercise designed to enhance physical fitness, and sleep–wake loop rectification. Physical motion, such as stamping, leg crossing, and slow standing with a bowed head, help prevent the flow of blood into the lower body parts and sustain cerebral circulation during an upright posture [51,52]. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid34729276 cited: true text: full license: by verdict: supports section: Discussion quote: The common protocols for the management of POTS symptoms include exercises in the recumbent position, such as physical counterpressure techniques, to help stabilize blood pressure and heart rate. note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid33723532 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Available management protocols for POTS (Table 2) aim at increasing intake of fluids (water) and salt, physical countermaneuvers, and individually adapted aerobic exercise in recumbent position (1,5,9) to help correct the physiological abnormalities. note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Discussion quote: The treatment of POTS requires a two-pronged approach. Conservative measures, including physical counter-maneuvres, immediately during a POTS attack is useful to abort episodes. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid30001836 cited: true text: full license: none verdict: supports section: 5. PHYSICAL COUNTERMEASURES quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p001, p021, p022. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Approach to therapy for patients with POTS > Nonpharmacologic interventions quote: Nonpharmacologic strategies include avoidance of exposures that may contribute to overheating, improving venous return by activation of calf muscles and tonic muscle contraction when lightheaded. note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid26199795 cited: true text: full license: none verdict: supports section: Discussion > Therapy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26199795. Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Management quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p029, p026. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Treatments and Therapies > Non-pharmacologic Therapies quote: Physical maneuvers such as leg crossing, muscle pumping, and squatting may improve acute symptom onset.[60] note: 'Found by winnow, kev and lev in p045. Claude judged: partial.' - edge: - serotonergic_therapy - treats - pots papers: 8 evidence: - paper: pmid24227635 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24227635. Found by winnow, kev and lev in p007, p030, p001. Claude judged: supports.' - paper: pmid20309394 cited: true text: full license: by-nc-nd verdict: supports section: Results > Response to Medical therapy quote: 'Pharmacotherapy was used alone or in combination in the following order: fludrocortisone 0.1mg po bid, midodrine 5-10 mg po tid, propanolol10 mg po tid, pyrodostigmine 60 mg po bid, serotonin reuptake inhibitor or modafinil 100 mg po qam.' note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid40454385 cited: true text: full license: by verdict: partial section: Discussion quote: According to the patient’s condition, treatment with paroxetine hydrochloride was initiated, resulting in a significant improvement in POTS symptoms and a rapid cessation of progressive syncope episodes. note: 'Found by winnow, kev and lev in p008, p012, p003. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Treatments and Therapies > Pharmacologic Therapies > Medications with Undefined Mechanisms or Subtype-specific Targets quote: Selective serotonin reuptake inhibitors (SSRIs) have demonstrated symptomatic improvement in POTS patients.[75] These medications increase monoamine neurotransmitter availability in the synaptic cleft to increase neurotransmission.[75] note: 'Found by winnow, kev and lev in p056. Claude judged: partial.' - paper: pmid35870963 cited: true text: full license: by verdict: partial section: Discussion quote: For example, both orthostatic intolerance and co-morbid anxiety/depression would be expected to respond to serotonin reuptake inhibitors. note: 'Found by winnow, kev and lev in p018, p031, p041. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Treatment > Pharmacologic interventions quote: A review of studies and literature has suggested that the most effective and useful medications in the treatment of POTS may be certain beta-blockers, selective serotonin reuptake inhibitors (SSRIs), and fludrocortisone.2 note: 'Found by winnow, kev and lev in p036, p034. Claude judged: partial.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: Recovery > Management of POTS and Associated Conditions > Medications for Blood Flow quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p090. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p038. Claude judged: partial.' - edge: - auricular_vagus_nerve_stimulation - treats - pots papers: 6 evidence: - paper: pmid42342403 cited: true text: full license: by verdict: supports section: Introduction > Background and rationale quote: Notably, a recent double-blind, sham-controlled trial study20 revealed that daily AVNT for 2 months notably enhances postural tachycardia and autonomic symptoms, indicating improved autonomic control and vascular function without affecting BP. AVNT has also been associated with improved autonomic regulation and reduced inflammatory markers, highlighting its therapeutic potential in POTS. note: 'Found by winnow, kev and lev in p008, p133, p002. Claude judged: supports.' - paper: pmid40014480 cited: true text: full license: by verdict: supports section: Discussion > LL‐TS and POTS quote: Therefore, that LL‐TS is a noninvasive neuromodulation in autonomic balance for individuals with POTS following post‐acute COVID‐19 infection. note: 'Found by winnow, kev and lev in p025, p003, p007. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: 'Transcutaneous Vagus Nerve Stimulation in POTS > tVNS and POTS: Clinical Evidence' quote: In another open-label clinical trial, 4 hours of tVNS daily at the cymba conchae region for 14 days was associated with a significant reduction in orthostatic intolerance and gastrointestinal symptoms in POTS patients.[45] A tendency of reduced HR following standing posture was also noted in the tVNS group. note: 'Found by winnow, kev and lev in p020, p004, p015. Claude judged: supports.' - paper: pmid37999672 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37999672. Found by winnow, kev and lev in p023, p003, p004. Claude judged: supports.' - paper: pmid37705568 cited: true text: full license: by verdict: supports section: Discussion quote: Auricular vagus nerve stimulation has also been reported to be useful for POTS [47]. note: 'Found by winnow, kev and lev in p051. Claude judged: supports.' - paper: pmid37631004 cited: true text: full license: by verdict: partial section: 8. Electroceutical Therapy for Autoimmune Disease > 8.7. Postural Orthostatic Tachycardia Syndrome (POTS) quote: The observation that LLTS ameliorated autoantibody-induced autonomic dysfunction and inflammation suggests that noninvasive stimulation could offer a novel, effective, safe neuromodulatory therapeutic strategy for patients with POTS, particularly those suffering from the hyperadrenergic subtype. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - edge: - offending_medication_withdrawal - treats - pots papers: 6 evidence: - paper: pmid42037960 cited: true text: full license: by verdict: supports section: Discussion quote: Pharmacologic intervention in POTS patients usually begins with discontinuation of medications that may exacerbate tachycardia or hypovolemia, such as vasodilators, diuretics, and serotonin-norepinephrine reuptake inhibitors (SNRIs). note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid39109119 cited: true text: full license: by verdict: supports section: Discussion quote: The first step in pharmacological treatment is to discontinue medications that might contribute to tachycardia [22]. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: supports section: Patient management quote: Based on current evidence, the Canadian Cardiovascular Society recommends non-pharmacological therapy as the first line management approach – withdrawal of exacerbating medications, increasing blood volume with dietary interventions, use of compression stockings, adoption of head-up tilt sleeping position, and semi-recumbent exercises [39]. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid34327047 cited: true text: full license: by verdict: supports section: Methods > Management > Nonpharmacologic management quote: Nonpharmacologic management options are first-line therapies.1,11 This includes cessation of medications that may worsen POTS, such as norepinephrine reuptake inhibitors.1 note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid26241226 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: Management of POTS is multifaceted and includes discontinuation of any medications that could contribute to orthostatic intolerance, such as α-adrenoceptor antagonists, diuretics, cGMP-specific phosphodiesterase type 5 inhibitors (sildenafil), and organic nitrates and nitrites, along with identifying those conditions that may cause secondary POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid23217691 cited: true text: full license: none verdict: supports section: POSTURAL TACHYCARDIA SYNDROME > Non-Pharmacological Treatment of POTS (Table 4) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23217691. Found by winnow, kev and lev in p012. Claude judged: supports.' - edge: - antihistamine_therapy - treats - mast_cell_activation papers: 3 evidence: - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: For example, pacing is recommended care to manage energy levels and avoid PEM in ME/CFS; fluid/electrolytes, compression stockings and Mestinon to help manage OI; beta-blockers and ivabradine to aid tachycardia present in POTS; IgG for use in immune dysfunction; antihistamines (H1 and/or H2 inhibitors) and other select treatments to manage MCAS; low-dose naltrexone to manage pain; and melatonin to mitigate sleep problems. note: 'Found by winnow, kev and lev in p033, p014. Claude judged: supports.' - paper: pmid38003876 cited: true text: full license: by verdict: supports section: 2. Materials and Methods quote: Medical therapy starts with a combination of non-sedating histamine receptor 1 and histamine receptor 2 blockers twice daily [9]. If the response is inadequate or the patients have significant symptoms, they receive additional over-the-counter MC stabilizing agents such as vitamins C and D and quercetin, a flavonoid. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: supports.' - paper: pmid38867988 cited: true text: full license: by-nc verdict: partial section: Case presentation > History quote: Additionally, mast cell activation syndrome (MCAS) was suspected given relief with cetirizine. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - edge: - prokinetic_therapy - treats - gi_dysmotility papers: 2 evidence: - paper: pmid42509985 cited: true text: full license: by verdict: supports section: 3. Discussion quote: This case series describes three adolescent females with specialist-confirmed dysautonomia and refractory GI dysmotility who were treated with a standardized short-course, low-dose metoclopramide bridge protocol as part of a multidisciplinary management approach. To our knowledge, this is the first published report specifically describing metoclopramide as a targeted prokinetic bridge strategy in a pediatric dysautonomia population. note: 'Found by winnow, kev and lev in p003, p022, p025. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: Recovery > Management of POTS and Associated Conditions > Medications for Gastrointestinal Function quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p094, p095. Claude judged: partial.' - edge: - exercise_reconditioning - treats - long_covid papers: 2 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 7. Treatment quote: In the case of POTS related to SARS-CoV-2 infection, published cases have supported the recommendation of various non-pharmacological interventions, such as increased salt and fluid intake (unless contraindicated), waist-high compression garments, and regular and graduate-supervised exercises (84, 85). The utility of an exercise program in a recumbent or semi-recumbent position (rowing or cycling) for 8 weeks, followed by a subsequent 4-week jogging phase, has been demonstrated (86). note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - paper: pmid39198662 cited: true text: full license: by verdict: partial section: Abstract quote: Evidence for different treatments of POTS and PCC is limited, and this study aimed to evaluate the feasibility of individually tailored physical exercise. note: 'Found by winnow, kev and lev in p001, p026. Claude judged: partial.' - edge: - immunomodulatory_therapy - treats - mast_cell_activation papers: 2 evidence: - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Discussion quote: This is the first case to our knowledge where immunotherapy with IVIg led to significant and sustained improvement in MCAS as has been seen in publications of autoimmune neuromuscular diseases and a single case of POTS.9 10 Other patients with MCAS have had response in their MC symptoms to IVIg.2 note: 'Found by winnow, kev and lev in p011, p001, p014. Claude judged: supports.' - paper: pmid38003876 cited: true text: full license: by verdict: partial section: 7. Mast-Cell-Directed Treatment quote: In a case report, a MCAS patient with severe MCAS and postural orthostatic tachycardia syndrome experienced significant improvement with regard to depression, anxiety, and dysautonomia symptoms using intravenous immunoglobulin, LDN, and antibiotic treatment for small intestinal bacterial overgrowth [21]. note: 'Found by winnow, kev and lev in p027. Claude judged: partial.' - edge: - serotonergic_therapy - treats - anxiety_depression papers: 1 evidence: - paper: pmid40454385 cited: true text: full license: by verdict: supports section: Introduction quote: Research showed that paroxetine has unique pharmacological and clinical properties compared with other selective serotonin reuptake inhibitors (SSRIs). It effectively alleviates symptoms of anxiety disorders, such as social anxiety disorder, with efficacy comparable to other SSRIs. note: 'Found by winnow, kev and lev in p008, p012, p003. Claude judged: supports.' - edge: - auricular_vagus_nerve_stimulation - treats - long_covid papers: 1 evidence: - paper: pmid40014480 cited: true text: full license: by verdict: supports section: Abstract > Objectives quote: We conducted controlled, prospective, and randomized clinical trials to explore the potential therapeutic benefits of low‐level tragus stimulation (LL‐TS) in patients with POTS following COVID‐19 infection. note: 'Found by winnow, kev and lev in p025, p002, p003. Claude judged: supports.' - edge: - immunomodulatory_therapy - treats - long_covid papers: 1 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Conclusion quote: Combining the limited data outlined in this review, the current and future clinical trials, and our clinical experience, we conclude that immunologic therapies present an important and, potentially, very effective therapeutic option for patients with POTS, OCADs, and Long COVID. To this end, we believe that patients with severe POTS, OCADs, and Long COVID should have access to a variety of therapeutic options involving immunomodulation, including a 3–6-month trial of IVIG, SCIG, or plasmapheresis—therapies that are already available to patients with demyelinating neuropathies, autonomic neuropathy, autoimmune autonomic ganglionopathy, and other neurologic and autoimmune disorders. note: 'Found by winnow, kev and lev in p040, p029, p035. Claude judged: supports.' - edge: - ivabradine_therapy - treats - long_covid papers: 1 evidence: - paper: pmid35853576 cited: true text: full license: none verdict: supports section: Management of post–COVID-19 POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p026. Claude judged: supports.' - edge: - lifestyle_modification - treats - long_covid papers: 1 evidence: - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 7. Treatment quote: It is advisable to avoid situations that can exacerbate symptoms, which has also been shown to be beneficial in POTS after SARS-CoV-2 infection (Table 1) (17, 87, 88). note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - droxidopa_therapy - treats - pots papers: 1 evidence: - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: partial section: Results > Clinical management quote: Propranolol and droxidopa were eventually added, resulting in symptom reduction and improved orthostatic tolerance [18]. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - phenobarbital_therapy - treats - pots papers: 1 evidence: - paper: pmid19207771 cited: true text: full license: none verdict: partial section: Management > Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p029. Claude judged: partial.' - edge: - immunomodulatory_therapy - treats - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid41403551 cited: true text: full license: by-nc-sa verdict: supports section: Abstract quote: This case demonstrates that symptoms and signs of SFN as a manifestation of PACVS may benefit from the administration of IVIGs even years after onset. note: 'Found by winnow, kev and lev in p001, p006, p004. Claude judged: supports.' - edge: - immunomodulatory_therapy - treats - systemic_autoimmune_disease papers: 1 evidence: - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Immunotherapies > Immunologic therapies and ongoing clinical trials for POTS and other common autonomic disorders > Other traditional immunomodulators quote: They have been reported for treatment of autonomic dysfunction either as monotherapy or in combination with other immunotherapies in patients with neurologic Sjögren’s syndrome and autonomic neuropathy associated with neurosarcoidosis (Flanagan et al., 2014; Goodman, 2014; Pang et al., 2017; Oishi et al., 2021; Kataria et al., 2023). note: 'Found by winnow, kev and lev in p029. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - pots papers: 92 evidence: - paper: pmid42691689 cited: true text: full license: none verdict: supports section: Autonomic system degenerations, generalized dysautonomia, and disorders of autonomic dysregulation > Postural orthostatic tachycardia syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42691689. Found by winnow, kev and lev in p044. Claude judged: supports.' - paper: pmid42509985 cited: true text: full license: by verdict: supports section: 3. Discussion > 3.1. Dysautonomia and the Rationale for Prokinetic Bridge Therapy quote: 'Patient 3 illustrates a further layer of this pathophysiology: the overlap between POTS, hypermobile Ehlers–Danlos syndrome (hEDS), and disorders of gut–brain interaction.' note: 'Found by winnow, kev and lev in p027, p036. Claude judged: supports.' - paper: pmid42037722 cited: true text: full license: by verdict: supports section: Mechanistic phenotypes supporting a compensatory framework > Venous pooling and connective tissue laxity quote: Cross-sectional data show that a substantial minority of POTS patients meet clinical criteria for hypermobile Ehlers-Danlos syndrome (hEDS) and many more exhibit generalized joint hypermobility. This overlap is clinically relevant because it increases the prior probability of pooling-dominant physiology and supports early use of lower-body and abdominal compression, counter-maneuvers, and volume expansion (7). note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Introduction quote: Patients with POTS often have a higher prevalence of various comorbidities, including chronic fatigue syndrome, syncope, migraines, fibromyalgia, joint hypermobility, Ehlers‐Danlos Syndrome, hypervigilance, anxiety, concussions, and autoimmune disorders [3]. note: 'Found by winnow, kev and lev in p007, p029, p003. Claude judged: supports.' - paper: pmid41924132 cited: true text: full license: by-nc verdict: supports section: Introduction quote: POTS (a form of dysautonomia) has been described in >50% of patients with EDS/HSD.6 note: 'Found by winnow, kev and lev in p008, p009, p028. Claude judged: supports.' - paper: pmid41898333 cited: true text: full license: by verdict: supports section: 11. Vascular Compression Syndromes and HSD quote: Additionally, a study evaluating the incidence of vTOS in patients with POTS identified that 70% patients also had EDS [129]. note: 'Found by winnow, kev and lev in p033, p001, p013. Claude judged: supports.' - paper: pmid41858767 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: Patients with postural orthostatic tachycardia syndrome (POTS) often suffer from gastrointestinal symptoms and concomitant hypermobility spectrum disorders, such as hypermobile Ehlers-Danlos syndrome (hEDS). note: 'Found by winnow, kev and lev in p001, p007, p003. Claude judged: supports.' - paper: pmid41801611 cited: true text: full license: by verdict: supports section: Introduction quote: Up 80% of patients with hEDS present with syndromes of OI, such as orthostatic hypotension (OH) or POTS [17–19]. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: POTS is well known to be associated with several conditions, such as chronic fatigue syndrome and joint hypermobility, specifically Ehlers-Danlos syndrome type III, which have been linked to extra-articular manifestations such as dysautonomia and POTS [15]. note: 'Found by winnow, kev and lev in p003, p080, p086. Claude judged: supports.' - paper: pmid41301791 cited: true text: full license: by verdict: supports section: 4. Neurologic Evaluation > 4.2. Examination quote: Assessment for joint hypermobility with the Beighton scale is recommended because hypermobility spectrum disorders and hypermobile Ehlers–Danlos syndrome (EDS) are highly prevalent in patients with presyncope, vasovagal syncope and POTS [25]. note: 'Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid41282714 cited: true text: full license: by verdict: supports section: Discussion quote: Comorbid conditions commonly observed in hEDS, including MCAS, POTS, and ME/CFS, were significantly more prevalent in patients with hEDS with Long COVID than in those without. note: 'Found by winnow, kev and lev in p002, p009, p045. Claude judged: supports.' - paper: pmid41156242 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Other studies have noted an association between POTS and JH, and it has been estimated that over half with POTS have generalised joint laxity, although our experience would suggest that this is an underestimate [24]. note: 'Found by winnow, kev and lev in p004, p016, p020. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 4 Discussion quote: Finally, we did not assess cohorts for hypermobility spectrum disorders or hypermobile Ehlers–Danlos syndromes that are known to be associated with abnormal bleeding. As these conditions are common comorbidities in POTS, the δ-SPD we report in POTS patients, in contrast to our control cohorts, might be related to these connective tissue disorders rather than POTS. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: supports section: Abstract quote: Additionally, a strong association between POTS and Ehlers–Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. note: 'Found by winnow, kev and lev in p015, p017, p001. Claude judged: supports.' - paper: pmid40624434 cited: true text: full license: by verdict: supports section: Clinical features and evaluation of dysautonomia quote: Assessment for joint hypermobility with the Beighton scale is warranted in patients with dysautonomia to identify hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (EDS), which are highly prevalent in patients with POTS, post-COVID dysautonomia and other forms of dysautonomia [22]. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid40546538 cited: true text: full license: by verdict: supports section: Discussion quote: Approximately 20%-30% of the POTS population also meets the diagnostic criteria for EDS [16]. note: 'Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid40530951 cited: true text: abstract license: none verdict: supports section: Abstract > Context quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40530951. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid40520610 cited: true text: full license: by verdict: supports section: Discussion quote: Approximately 59% of our PoTS cohort have a diagnosis of hypermobility, similar to the combined finding of 55% described by Miller et al. in the first cross-sectional prospective study evaluating the prevalence of hypermobile EDS and general joint hypermobility in PoTS (23). To the best of our knowledge, despite being well documented as an association, it is not known why PoTS and EDS/hypermobility syndrome overlap, nor why there is an association with migraine. note: 'Found by winnow, kev and lev in p031, p006. Claude judged: supports.' - paper: pmid40387691 cited: true text: abstract license: none verdict: supports section: Abstract > Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40387691. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid40352770 cited: true text: full license: by verdict: supports section: Abstract > Background quote: The close association of syndromes of orthostatic intolerance with and without postural orthostatic tachycardia syndrome (POTS) with Joint Hypermobility Disorders (JHD) including Hypermobility Spectrum Disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS) and with Mast Cell Activation Syndrome (MCAS) is now firmly established. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid39875497 cited: true text: full license: by verdict: supports section: Discussion quote: It is noteworthy that hEDS exhibits a high concurrence with POTS with up to 30% of patients meeting diagnostic criteria for both conditions and the reduced venous return due to vascular laxity and blood pooling may be responsible for reduced CBF in this population29. note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid39850941 cited: true text: full license: by-nc verdict: supports section: Discussion quote: "Our sample also displayed high rates of comorbid conditions, including POTS (32.2%) and mast cell activation\ \ disorder (16.9%), consistent with existing literature suggesting potential associations among POTS, hEDS,\ \ and mast cell activation disorder.\n13\n One study of 91 patients with POTS found that 31% met clinical\ \ criteria for hEDS." note: 'Found by winnow, kev and lev in p024, p003. Claude judged: supports.' - paper: pmid39582682 cited: true text: full license: by verdict: supports section: Headache disorders in hEDS and HSD > Orthostatic headaches > Postural tachycardia syndrome quote: The exact mechanism behind increased prevalence of PoTS in hypermobile patients remains elusive. One of the more accepted hypotheses relates to excessive distensibility of the veins, due to the underlying HCTD, leading to venous pooling and reduced venous return. note: 'Found by winnow, kev and lev in p021, p024, p013. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Hypermobile Ehlers–Danlos Syndrome and Hypermobility Spectrum Disorder quote: Autonomic dysfunction/POTS is also often a component of hEDS and HSD, with symptoms, such as hypotension, orthostasis, dizziness, palpitations, exercise intolerance, and memory/concentration problems.[18] note: 'Found by winnow, kev and lev in p018, p023, p024. Claude judged: supports.' - paper: pmid39301475 cited: true text: full license: by verdict: supports section: Introduction quote: Joint hypermobility has been detected in up to 57% of patients with POTS, 49% of patients with ME/CFS, 30% of patients with LC, and 27% of patients with fibromyalgia, compared to 10–20% in the general population (5, 9–12). note: 'Found by winnow, kev and lev in p001, p003, p007. Claude judged: supports.' - paper: pmid39268060 cited: true text: full license: by verdict: supports section: Abstract quote: There has been an increasingly reported association between Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS) and gastrointestinal disorders. note: 'Found by winnow, kev and lev in p042, p071, p001. Claude judged: supports.' - paper: pmid38958137 cited: true text: full license: by-nc-nd verdict: supports section: DISCUSSION quote: The findings of migraine, Ehlers–Danlos syndrome, irritable bowel syndrome, and mast cell activation syndrome seen comorbidly in this cohort have been previously associated with POTS. note: 'Found by winnow, kev and lev in p040. Claude judged: supports.' - paper: pmid38912309 cited: true text: full license: by verdict: supports section: Discussion and conclusion quote: '‘Reported comorbidities in children with POTS mainly include allergic disorders, migraine, psychological disorders, hyperventilation syndrome, chronic fatigue syndrome, hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder (hEDS/HSD), gastrointestinal dysfunction, and fibromyalgia’ (Wang et al., 2021: 8946). Current understandings of comorbidities of PoTS tend to vary with some links seeming likely but not well understood.' note: 'Found by winnow, kev and lev in p043, p003, p018. Claude judged: supports.' - paper: pmid38673548 cited: true text: full license: by verdict: supports section: 4. Discussion > 4.3. Sexual Dysfunction and Neurologic Disorders quote: Given a high prevalence of comorbidity between POTS and EDS, there may also be increased rates of these gynecologic complications in POTS patients. note: 'Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid38545281 cited: true text: full license: by verdict: supports section: Results quote: JH+ were significantly more likely to self-report EDS (29% vs. 3%, p < 0.001) and POTS (33% vs. 20%, p ≤ 0.001). note: 'Found by winnow, kev and lev in p027, p004, p023. Claude judged: supports.' - paper: pmid38469013 cited: true text: full license: by verdict: supports section: Discussion quote: Therapies vary widely for POTS, and successful treatment may be viewed as an art focused on symptom improvement and treatment of comorbid or underlying conditions rather than a standardized algorithm [11]. Associations with multiple disorders have been identified, such as EDS described above and more recently COVID, and may provide insight into previously unrecognized etiologies, novel pathophysiology, and optimal management of patient symptoms [10-13]. note: 'Found by winnow, kev and lev in p009, p008. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Hypermobile spectrum disorders (HSD) including hypermobile Ehlers-Danlos syndrome (hEDS) are also more common in POTS (Miller et al., 2020; Tai et al., 2020). note: 'Found by winnow, kev and lev in p002, p021, p037. Claude judged: supports.' - paper: pmid38275067 cited: true text: full license: by verdict: supports section: STUDIES ON POTS AND HEDS quote: There is a strong correlation between POTS and hEDS, and it has been suggested that if an individual meets the criterion for POTS, they should also be screened for hEDS [58, 63]. note: 'Found by winnow, kev and lev in p009, p010, p002. Claude judged: supports.' - paper: pmid38162438 cited: true text: full license: by verdict: supports section: Discussion > Postural orthostatic tachycardia syndrome quote: Over half of patients with POTS were found to experience orthostatic headache (24), and POTS is common amongst patients on the hypermobility spectrum (25). note: 'Found by winnow, kev and lev in p002, p014. Claude judged: supports.' - paper: pmid37234076 cited: true text: full license: by verdict: supports section: 'Female reproductive health in illnesses comorbid or associated with Long COVID: A brief overview of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS), and endometriosis > Ehlers-Danlos syndrome (EDS), connective tissue disorders (CTDs), and reproductive health' quote: CTDs, including EDS and its largest subtype hypermobile EDS (hEDS) (56), are relatively common in patients with ME/CFS and POTS (57, 58). note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid36908200 cited: true text: full license: none verdict: supports section: 'Discussion: > Interpretation: > Comorbid EDS:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36908200. Found by winnow, kev and lev in p040, p042, p011. Claude judged: supports.' - paper: pmid36694653 cited: true text: full license: by verdict: supports section: INTRODUCTION quote: Additional consideration must also be given to the comorbidities that exist alongside the main condition due to its multisystemic nature. These include Postural Tachycardia Syndrome (PoTS), note: 'Found by winnow, kev and lev in p002, p005, p012. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Results > Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders quote: The most common type is hEDS, but hypermobility spectrum disorders (HSD) that encompass patients who do not qualify for a diagnosis of hEDS are also common among patients with POTS.36,37 The prevalence of hEDS/HSD in POTS is high, with reports of 31% of POTS patients meeting the criteria for hEDS and a further 24% for non-hEDS generalized joint hypermobility.36,37 note: 'Found by winnow, kev and lev in p021, p017, p024. Claude judged: supports.' - paper: pmid36437696 cited: true text: abstract license: none verdict: supports section: Abstract > Background And Purpose quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36437696. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid36000435 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: POTS has been associated with conditions causing peripheral autonomic denervation and connective tissue disorders (Joint hypermobility syndrome, Ehlers‐Danlos syndrome), chronic fatigue syndrome, autoimmune disorders, and deconditioning. note: 'Found by winnow, kev and lev in p010, p029. Claude judged: supports.' - paper: pmid35620060 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Postural orthostatic tachycardia syndrome is found in 15–41% of patients with EDS.3 note: 'Found by winnow, kev and lev in p005, p008, p016. Claude judged: supports.' - paper: pmid35557616 cited: true text: full license: by verdict: supports section: Conclusion quote: This study describes a higher prevalence of POTS in patients with PANS than in the general pediatric population and an association of POTS with comorbidities such as joint hypermobility, anxiety, chronic fatigue, and family history of cardiovascular issues. note: 'Found by winnow, kev and lev in p039, p003, p026. Claude judged: supports.' - paper: pmid35525992 cited: true text: full license: by verdict: supports section: Background quote: Hypermobility spectrum disorders (HSD) are a common comorbidity [5]. note: 'Found by winnow, kev and lev in p008, p016. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What other conditions commonly occur in patients with POTS? quote: Common comorbid conditions seen with POTS4,21 include hypermobile Ehlers–Danlos syndrome, mast cell activation syndrome,22 migraine and ME/CFS (Table 1).18 note: 'Found by winnow, kev and lev in p018, p006, p017. Claude judged: supports.' - paper: pmid35224842 cited: true text: full license: by-nc-nd verdict: supports section: INTRODUCTION quote: The prevalence of POTS was found to be greater in the EDS‐HT (41%) than control (11%) group; the prevalence of OH was lower (~26%) but not significantly different between groups. note: 'Found by winnow, kev and lev in p004, p043, p001. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: The co-existence of POTS and hEDS/HSD in adults was reported.44 The findings revealed that 22.7% of pediatric POTS had EDS and 39.0% had hypermobility spectrum disorder (HSD).45 note: 'Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid34765384 cited: true text: full license: by verdict: supports section: Introduction quote: Further, EDS III is uniquely associated with postural orthostatic tachycardia syndrome (POTS) [4]. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid34510391 cited: true text: full license: none verdict: supports section: Overlap of Dysautonomia and Hypermobility Syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34510391. Found by winnow, kev and lev in p009, p010. Claude judged: supports.' - paper: pmid34246578 cited: true text: full license: by-nc-nd verdict: supports section: Pathophysiology of POTS quote: The associations of POTS with migraine headache, the hypermobile form of Ehlers-Danlos syndrome (hEDS) (De Wandele et al., 2014) and the hypermobility spectrum disorder, allergic disorders like mast cell activation syndrome (MCAS) (Shibao et al., 2005), and autoimmune disorders have been clearly described. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Clinical associations & co-morbidities quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid34055418 cited: true text: full license: by verdict: supports section: 3. Discussion quote: The association between POTS and JHS can be explained by predominant peripheral neuropathy in the autonomous system and a failure of the peripheral vascular system to maintain resistance in areas exposed to stress due to orthostasis, blood stasis in the lower limbs, or pathologies of the central nervous system [11]. note: 'Found by winnow, kev and lev in p005, p012, p002. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Na síndrome de Ehlers-Danlos, uma doença do tecido conjuntivo com hiperelasticidade da pele e hipermotilidade articular, 70% dos indivíduos apresentam SPOT e 18% dos pacientes com SPOT apresentam critérios diagnósticos para síndrome de Ehlers-Danlos, considerado um mecanismo subjacente para a síndrome.80 note: 'Found by winnow, kev and lev in p123. Claude judged: supports.' - paper: pmid33388686 cited: true text: abstract license: none verdict: supports section: Abstract > Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33388686. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid33244220 cited: true text: full license: by-nc verdict: supports section: Discussion quote: EDS has been associated with POTS, and prior studies on EDS have documented ocular manifestations of the disease, including dry eye syndrome.20 note: 'Found by winnow, kev and lev in p025, p033, p037. Claude judged: supports.' - paper: pmid32803794 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32803794. Found by winnow, kev and lev in p003, p004, p001. Claude judged: supports.' - paper: pmid31954224 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31954224. Found by winnow, kev and lev in p015, p016, p001. Claude judged: supports.' - paper: pmid29876157 cited: true text: full license: by verdict: supports section: Review quote: Connective tissue disorders, especially Ehler Danlos syndrome hypermobility type, have a high concurrence rate with POTS as found by Cohen and Markham [20]. note: 'Found by winnow, kev and lev in p011, p012. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: One-third of people with POTS have comorbid Ehlers-Danlos syndrome, a heterogeneous group of inherited connective tissues disorders associated with joint laxity, joint subluxations and dislocations, and arthralgia.66,67 The diagnosis of hypermobile Ehlers-Danlos syndrome, the most common form of Ehlers-Danlos syndrome seen in POTS, remains clinical as there is no genetic marker yet identified.68–70 note: 'Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Results > Postural Tachycardia Syndrome, Gastrointestinal Symptoms, and related co-morbidities GI symptoms in Postural Tachycardia Syndrome and Ehlers-Danlos quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p016, p001, p015. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 3. Diagnosis > 3.2 Clinical Features quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p008, p006. Claude judged: supports.' - paper: pmid29519641 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29519641. Found by winnow, kev and lev in p004, p001, p003. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Introduction > Concurrent clinical syndromes > Hypermobility syndrome quote: Concurrent hypermobility, often referred to as Ehlers Danlos Syndrome, is overrepresented in patients with POTS.13 The Beighton score is a standard tool used to document the presence of hypermobility.14 note: 'Found by winnow, kev and lev in p007, p002. Claude judged: supports.' - paper: pmid28286774 cited: true text: full license: by verdict: supports section: 1. Introduction quote: In particular, different authors described orthostatic intolerance (OI) and postural orthostatic tachycardia symptoms (POTS) in JHS/EDS-HT [10–13]. note: 'Found by winnow, kev and lev in p002, p024, p025. Claude judged: supports.' - paper: pmid27660311 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27660311. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Disorders Overlapping with POTS > Ehlers-Danlos Syndrome (EDS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p017, p018, p019. Claude judged: supports.' - paper: pmid25852449 cited: true text: full license: by verdict: supports section: Methods > Participants quote: Among the 11 PoTS patients, five had Ehlers-Danlos Syndrome—hypermobility type/joint hypermobility syndrome (EDS-HT/JHS) (Kanjwal et al., 2010; Mathias et al., 2012), which is frequently observed in PoTS patients. note: 'Found by winnow, kev and lev in p008, p025, p006. Claude judged: supports.' - paper: pmid25713509 cited: true text: full license: by verdict: supports section: Neurovisceral phenotypes > Joint hypermobility > Evidence of autonomic dysfunction in Joint Hypermobility quote: Orthostatic hypotension, postural tachycardia syndrome, and uncategorized orthostatic intolerance were found in over three-quarters of hypermobile patients compared to one tenth of controls. note: 'Found by winnow, kev and lev in p001, p009, p011. Claude judged: supports.' - paper: pmid25156902 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25156902. Found by winnow, kev and lev in p002, p001. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Typical Presentations of POTS > Physical Features quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: Secondary forms of POTS occur in association with other disorders, most commonly diabetes mellitus. Other conditions include amyloidosis, sarcoidosis, alcoholism, systemic lupus erythematosus, Sjögren’s syndrome, heavy-metal intoxication, joint hypermobility syndrome, pure autonomic failure, multiple-system atrophy and paraneoplastic syndrome [7]. note: 'Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid22143364 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22143364. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid42804409 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42804409. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid39308845 cited: true text: full license: by verdict: partial section: Introduction quote: Many patients with POTS may present with comorbid conditions, including but not limited to Ehlers-Danlos syndrome (EDS), mast cell activation, and autoimmune conditions [3]. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid38985772 cited: true text: full license: by verdict: partial section: Results > Overarching themes > Slowly moving forward and finding positive gains quote: You know, it felt like it was the last piece of the jigsaw, especially having hypermobile EDS. You know, I understand it kind of goes together. note: 'Found by winnow, kev and lev in p044. Claude judged: partial.' - paper: pmid38003876 cited: true text: full license: by verdict: partial section: 1. Introduction quote: The degree of morbidity is related to the quantity of the affected mast cells (MCs), the number of mutations within the mast cell (MC) lineage, the specific organ involvement, the presence of comorbid postural orthostatic tachycardia syndrome (POTS) and hypermobile Ehlers-Danlos syndrome (hEDS), and the impact of triggers [10,11,12,13]. note: 'Found by winnow, kev and lev in p001, p005, p028. Claude judged: partial.' - paper: pmid35673757 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35673757. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35269395 cited: true text: full license: by verdict: partial section: 4. Discussion quote: We lacked specific clinical histories for samples including Beighton scores used to assess hyperflexibility; some of the POTS patient group may have had hypermobility spectrum disorders (HSD) or hypermobile Ehlers–Danlos syndrome (h-EDS), which can be associated with easy bruising. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid34766441 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34766441. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid33677650 cited: true text: full license: none verdict: partial section: POTS and mechanical compression of brainstem quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33677650. Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid33562074 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Platelet δ-SPD is also common in Ehlers Danlos syndrome, a comorbidity we have identified in more than a third of our POTS patients. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid32489735 cited: true text: full license: by verdict: partial section: Abstract quote: 'In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p<0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p<0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility.' note: 'Found by winnow, kev and lev in p006, p008, p044. Claude judged: partial.' - paper: pmid32295399 cited: true text: full license: by verdict: partial section: Discussion quote: 'The patient had no known triggering factors but suffered from both EDS and POTS, possibly predisposing for NDPH.' note: 'Found by winnow, kev and lev in p006, p015. Claude judged: partial.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: partial section: 'Challenge I: Complexities And Misunderstandings' quote: 'Garland and colleagues (2015) wrote a well-organized review of POTS and its “overlapping pathophysiological mechanisms”: chronic fatigue syndrome, Ehler-Danlos Syndrome and other hypermobile joint syndromes, vasovagal syncope, panic attacks, pain, exercise, caffeine, sympathomimetic medications, anticholinergic medications, anemia, dehydration, and sinus tachycardia.32' note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid30755882 cited: true text: full license: by-nc-nd verdict: partial section: CASE 4 quote: The diagnosis of POTS syndrome associated with hypermobility syndrome was considered in this patient. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid30001836 cited: true text: full license: none verdict: partial section: 2. EXERCISE TRAINING > 2.1 Endurance training quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30001836. Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid29891041 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29891041. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid28986003 cited: true text: abstract license: none verdict: partial section: Abstract > Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28986003. Found by winnow, kev and lev in p002, p003, p004. Claude judged: partial.' - paper: pmid28924124 cited: true text: full license: by-nc-nd verdict: partial section: Case Report quote: An additional assessment of joint hyperextensibility according to the Beighton hypermobility scale was positive with a score of 5/9 (Table 1). Moreover, an orthostatic tolerance test showed apparent postural tachycardia (Fig. 2). note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid24934205 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Our finding of high levels of comorbidity, particularly CFS and EDS, is important as it might point towards an underlying overlapping mechanism.23–25 note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - paper: pmid22739942 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22739942. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid20376184 cited: true text: full license: by verdict: partial section: Abstract > Conclusions quote: Patients with POTS and JHS appear to become symptomatic at an earlier age compared to POTS patients without JHS. note: 'Found by winnow, kev and lev in p004, p014, p001. Claude judged: partial.' - paper: pmid19946638 cited: true text: full license: by verdict: partial section: 3. Discussion quote: In patients with POTS, the main mechanism is the consistent failure of the peripheral vascular system to increase resistance during upright posture. Patients with joint hypermobility syndrome even have more difficulty owing to loss of supporting connective tissues in the vessels. note: 'Found by winnow, kev and lev in p006, p007. Claude judged: partial.' - edge: - long_covid - associated_with - pots papers: 83 evidence: - paper: pmid42564177 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Although the SSRI/SNRI group demonstrated a lower overall incidence of any of the 23 long COVID symptoms/conditions (10.13% versus 18.14%), symptom/condition-specific analyses revealed higher risks for certain neurological and autonomic symptoms/conditions, such as POTS and cognitive dysfunction, and lower risks for fever, chills and hair loss. note: 'Found by winnow, kev and lev in p016, p001, p030. Claude judged: supports.' - paper: pmid42512077 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Clinical studies indicate an estimated 66–79% of patients with Long COVID exhibit symptoms of dysautonomia, with a substantial proportion meeting the diagnostic criteria of postural orthostatic tachycardia syndrome (POTS) [11,12,13]. note: 'Found by winnow, kev and lev in p004, p027, p001. Claude judged: supports.' - paper: pmid42279051 cited: true text: full license: by verdict: supports section: 1. Introduction quote: A SARS-CoV-2 infection can result in long-term cardiovascular dysautonomia (CVD) characterized by abnormal autonomic reflexes upon standing, with a subset meeting diagnostic criteria for Postural Tachycardia Syndrome (PoTS) [1]. note: 'Found by winnow, kev and lev in p002, p001, p004. Claude judged: supports.' - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 as part of Long COVID and is a common comorbidity of ME/CFS.8,9 note: 'Found by winnow, kev and lev in p007, p005, p012. Claude judged: supports.' - paper: pmid41300849 cited: true text: full license: by verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by excessive tachycardia during orthostatic stress. It is frequently observed in patients with syncope, Chronic Fatigue Syndrome (CFS), and post-COVID-19 syndrome (PCS), yet the underlying mechanisms may differ across these conditions. note: 'Found by winnow, kev and lev in p004, p001, p007. Claude judged: supports.' - paper: pmid41146789 cited: true text: full license: by verdict: supports section: Review quote: In addition to the aforementioned symptoms in the course of LC, in some cases, POTS may also occur. note: 'Found by winnow, kev and lev in p018, p001, p002. Claude judged: supports.' - paper: pmid41111962 cited: true text: full license: by verdict: supports section: Introduction quote: Both PoTS and OH have been noted in literature to be associated with long COVID (LC); a condition characterized by persistent symptoms, lasting greater than 12 weeks, experienced after recovering from an acute COVID-19 infection (8, 9). note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Introduction > Long COVID quote: Consequently, many patients with Long COVID have POTS or OCADs (Blitshteyn and Whitelaw, 2021; Davenport et al., 2024), with nearly 70% of patients having a high autonomic symptom burden (Larsen et al., 2022). note: 'Found by winnow, kev and lev in p013, p001, p019. Claude judged: supports.' - paper: pmid41050528 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Long COVID and one of its principal manifestations, postural orthostatic tachycardia syndrome (POTS), have become significant health challenges in the post-COVID-19 pandemic era. note: 'Found by winnow, kev and lev in p002, p001, p004. Claude judged: supports.' - paper: pmid41038948 cited: true text: full license: by verdict: supports section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. It is estimated that up to 70% of patients with PASC have POTS, with clinicians worldwide seeing an increasing number of POTS patients4. note: 'Found by winnow, kev and lev in p003, p013, p037. Claude judged: supports.' - paper: pmid41025260 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41025260. Found by winnow, kev and lev in p001, p003, p004. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 1 Introduction quote: This has led to POTS being a recognized complication of PASC. Clinicians with interests in dysautonomia have reported that up to 80% of PASC patients meet POTS diagnostic criteria (19–21). note: 'Found by winnow, kev and lev in p004, p006, p032. Claude judged: supports.' - paper: pmid40883051 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Background quote: Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID. note: 'Found by winnow, kev and lev in p001, p003, p006. Claude judged: supports.' - paper: pmid40864005 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40864005. Found by winnow, kev and lev in p001, p002, p006. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. note: 'Found by winnow, kev and lev in p007, p001, p006. Claude judged: supports.' - paper: pmid40692561 cited: true text: full license: by verdict: supports section: Discussion quote: Amidst this quandary, POTS has emerged as the most common form of autonomic dysfunction associated with LHC, with as many as 2.5% of those with LHC affected (58). note: 'Found by winnow, kev and lev in p005, p044, p001. Claude judged: supports.' - paper: pmid40660536 cited: true text: full license: by verdict: supports section: 'Abstract > Rationale:' quote: Postural orthostatic tachycardia syndrome (POTS) is a type of autonomic dysfunction that can occur following coronavirus disease (COVID-19) infection, particularly in adolescents. note: 'Found by winnow, kev and lev in p003, p015, p001. Claude judged: supports.' - paper: pmid40492086 cited: true text: full license: by-nd verdict: supports section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. It is estimated that up to 70% of patients with PASC have POTS, with clinicians worldwide seeing an increasing number of POTS patients 4. note: 'Found by winnow, kev and lev in p002, p009, p030. Claude judged: supports.' - paper: pmid40014480 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance and is frequently observed in post‐COVID conditions. note: 'Found by winnow, kev and lev in p001, p006, p023. Claude judged: supports.' - paper: pmid39919323 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39919323. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid39884840 cited: true text: full license: by-nc verdict: supports section: Background quote: The prevalence is thought to have increased since as autonomic dysfunction, including POTS, is one of the most reported post-acute sequelae of COVID-19, affecting up to half of those with long COVID (Larsen et al., 2022; Mallick et al., 2023). note: 'Found by winnow, kev and lev in p003, p027. Claude judged: supports.' - paper: pmid39882369 cited: true text: full license: by verdict: supports section: Introduction quote: One of the most common syndromes of PASC bears striking resemblance to POTS, and in some evaluations of PASC patients up to 79% were noted to meet diagnostic criteria for POTS (12). The overlap in these conditions has drawn significant interest, with questions of whether POTS developing as a syndrome of PASC should be managed similarly to non-PASC associated POTS or not (13, 14). note: 'Found by winnow, kev and lev in p001, p007, p016. Claude judged: supports.' - paper: pmid39875497 cited: true text: full license: by verdict: supports section: Introduction quote: Temporal association with viral infection is frequently reported and more recently POTS has been identified as the dominant phenotype in post-acute sequelae of COVID-19 (PASC)6,7. note: 'Found by winnow, kev and lev in p011, p002. Claude judged: supports.' - paper: pmid39857750 cited: true text: full license: by verdict: supports section: 2. POTS, Long COVID and the CNS quote: In the National Academies of Science definition of Long COVID, autonomic dysfunction, including POTS—one of the most common autonomic disorders—is listed as a major feature of Long COVID [3]. note: 'Found by winnow, kev and lev in p001, p006, p008. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Importantly, it was demonstrated in one study that, compared to people with Long COVID who did not experience IT, people with Long COVID and IT had higher rates of new-onset mast cell disorders (11% vs. 2.6%); neurologic conditions, including small fiber neuropathy (SFN) (22% vs. 8.3%); postural orthostatic tachycardia syndrome (POTS) (33% vs. 11%); and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (21% vs. 11%) [1]. note: 'Found by winnow, kev and lev in p005, p001, p002. Claude judged: supports.' - paper: pmid39838139 cited: true text: full license: by verdict: supports section: Discussion quote: Hence POTS, a syndrome most commonly triggered by viral infections, also associated with cognitive difficulties and highly prevalent among patients with LC, becomes a suitable option to achieve this objective. note: 'Found by winnow, kev and lev in p005, p044. Claude judged: supports.' - paper: pmid39775762 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid39741599 cited: true text: full license: by verdict: supports section: Abstract quote: SARS-CoV-2 infection (COVID-19) and the COVID-19 vaccine have been linked to the development of persistent symptoms, including orthostatic intolerance (OI) and postural orthostatic tachycardia syndrome (POTS), in both children and adults. note: 'Found by winnow, kev and lev in p031, p002, p008. Claude judged: supports.' - paper: pmid39554298 cited: true text: full license: by-nc verdict: supports section: INTRODUCTION quote: Several complications that exist in the background of long COVID have been reported. Seeley et al. showed that 79% of patients with long COVID meet the diagnostic criteria of postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p007, p019, p020. Claude judged: supports.' - paper: pmid39523946 cited: true text: full license: by-nc-nd verdict: supports section: 'Abstract > BACKGROUND:' quote: Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. note: 'Found by winnow, kev and lev in p003, p001, p002. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Among the multitude of symptoms associated with long-term COVID-19, POTS has emerged as a significant clinical issue, marking a notable increase in prevalence and recognition in the context of the pandemic [58]. The mechanisms behind this association are not fully elucidated but may involve inflammation, microthrombi, and autoimmunity [59,60]. note: 'Found by winnow, kev and lev in p014, p019, p020. Claude judged: supports.' - paper: pmid39198662 cited: true text: full license: by verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) occurs in approximately 30% of people with highly symptomatic post-COVID-19 condition (PCC). note: 'Found by winnow, kev and lev in p001, p004, p026. Claude judged: supports.' - paper: pmid39076856 cited: true text: full license: by verdict: supports section: Abstract quote: "Long COVID or post-acute Coronavirus disease 2019 (COVID-19), a malady defined \nby the persistence\ \ of COVID-19 symptoms for weeks or even months, is expected to \naffect the lives of millions of individuals\ \ worldwide significantly. \nCardiopulmonary symptoms such as chest discomfort, shortness of breath, fatigue,\ \ \nand autonomic manifestations such as postural orthostatic tachycardia syndrome, \nand arrhythmias are\ \ prevalent and widely recognized." note: 'Found by winnow, kev and lev in p043, p001, p042. Claude judged: supports.' - paper: pmid38585346 cited: true text: full license: by verdict: supports section: Abstract > Background quote: A subset of these long-hauler patients experienced symptoms of autonomic dysfunction and tested positive for postural orthostatic tachycardia syndrome (POTS) via autonomic testing. note: 'Found by winnow, kev and lev in p007, p001, p002. Claude judged: supports.' - paper: pmid38392604 cited: true text: full license: by verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of a variety of chronic, inflammatory diseases, including long COVID, as are small, insoluble, ‘fibrinaloid’ microclots. note: 'Found by winnow, kev and lev in p004, p006, p001. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Introduction quote: Over half of patients with POTS report a preceding infection (3). COVID-19 is increasingly recognized as a cause of POTS (4, 5), as well as other infections including Epstein Barr Virus (EBV) (6, 7). note: 'Found by winnow, kev and lev in p003, p034. Claude judged: supports.' - paper: pmid38240001 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Coronavirus disease 2019 (COVID‐19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. note: 'Found by winnow, kev and lev in p001, p003, p009. Claude judged: supports.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: The syndrome is regarded to be the most prevalent cardiovascular dysautonomia and a primary phenotype/subsyndrome in the post-acute COVID-19 syndrome that can develop after SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: supports.' - paper: pmid37981644 cited: true text: full license: by verdict: supports section: Abstract quote: Post-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p002, p001, p003. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: Abstract quote: The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. note: 'Found by winnow, kev and lev in p001, p015, p003. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Introduction quote: Recently, several case reports showed an increasing incidence of POTS as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients who had chronic signs and symptoms of the infection (long COVID (coronavirus disease)). note: 'Found by winnow, kev and lev in p001, p002, p009. Claude judged: supports.' - paper: pmid37391116 cited: true text: full license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p023, p001, p004. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Long Covid—the new pandemic quote: An emerging but incompletely understood phenomenon increasingly seen in Long Covid and syncope clinics is cardiovascular autonomic dysfunction including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension. Study of this apparent association with Long Covid may reveal underlying mechanisms and offer insight into non-Covid autonomic disorders with comprehension of autonomic nervous and neuroimmune system interaction. note: 'Found by winnow, kev and lev in p008, p009, p026. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. note: 'Found by winnow, kev and lev in p021, p001, p004. Claude judged: supports.' - paper: pmid37030518 cited: true text: full license: none verdict: supports section: Recommended Treatments for Long-term Cardiovascular Symptoms of COVID-19 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37030518. Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Abstract quote: POTS (Postural Orthostatic Tachycardia Syndrome) is a multisystem disorder characterized by the abnormal autonomic response to an upright posture, causing orthostatic intolerance and excessive tachycardia without hypotension. Recent reports suggest that a significant percentage of COVID-19 survivors develop POTS within 6 to 8 months of infection. note: 'Found by winnow, kev and lev in p003, p012, p001. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Abstract quote: The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. note: 'Found by winnow, kev and lev in p005, p001, p015. Claude judged: supports.' - paper: pmid36732397 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid36639608 cited: true text: full license: none verdict: supports section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p004, p024, p025. Claude judged: supports.' - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: However, even more interesting is the extremely high prevalence of POTS among patients with the post-COVID syndrome (6/8 (75.0%) versus 1/9 (11.1%) in the control group, p = 0.02). note: 'Found by winnow, kev and lev in p035, p046, p054. Claude judged: supports.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Postural orthostatic tachycardia syndrome has recently been identified in ∼20% of patients with post-acute sequelae of COVID-19 (PASC). note: 'Found by winnow, kev and lev in p001, p002, p005. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Introduction quote: These persistent symptoms have been termed post-acute COVID-19 syndrome or long-COVID6. Among these symptoms, several are associated with neurological disorders, notably postural orthostatic tachycardia syndrome (POTS)6. note: 'Found by winnow, kev and lev in p003, p030, p001. Claude judged: supports.' - paper: pmid36074973 cited: true text: full license: none verdict: supports section: 'Selected Etiology: Post-COVID-19 > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p107, p111. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p003, p010. Claude judged: supports.' - paper: pmid35852546 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p012, p001, p011. Claude judged: supports.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Although it is unknown how many more patients are seeking care as a result of COVID-19 than they were before the pandemic, American Autonomic Society statement reports suggest a sharp rise in instances, the majority of which are linked to long-COVID-19 [10]. These data suggest that POTS may be significantly related to COVID-19. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid35381331 cited: true text: full license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p001, p004, p006. Claude judged: supports.' - paper: pmid35355961 cited: true text: full license: by verdict: supports section: “Post-COVID-19 Tachycardia Syndrome” quote: From a cardiovascular point of view, recent papers have highlighted an association between orthostatic intolerance (OI), including orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS), with long COVID (17–19). note: 'Found by winnow, kev and lev in p004, p001, p002. Claude judged: supports.' - paper: pmid35269395 cited: true text: full license: by verdict: supports section: 1. Introduction quote: With associations of viral infections as a potential etiology of POTS and evidence that many COVID-19 long haulers are developing POTS, platelets may also play a significant role in the etiology or perpetuation of the disorder. note: 'Found by winnow, kev and lev in p003, p002. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Abstract > Background quote: Postural tachycardia syndrome (PTS) is a novel identified sequela of COVID-19 infection. This observational study describes clinical presentation, testing, and treatment response in seven patients diagnosed with PTS following COVID-19 infection. note: 'Found by winnow, kev and lev in p012, p001, p002. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 4. Postural Orthostatic Tachycardia Syndrome after COVID-19 quote: In March 2021, the American Autonomic Society (AAS) issued a statement concerning the clinical overlap of PASC with POTS [4]. The AAS stated that most PASC symptoms can be suggestive of POTS when the patient also suffers from excessive orthostatic tachycardia, and that further, in-depth studies are needed to elucidate the duration of post-COVID CVAD, its underlying pathophysiology, and optimum treatment. note: 'Found by winnow, kev and lev in p008, p018, p028. Claude judged: supports.' - paper: pmid34729276 cited: true text: full license: by verdict: supports section: Abstract quote: A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. note: 'Found by winnow, kev and lev in p002, p001, p003. Claude judged: supports.' - paper: pmid34607799 cited: true text: full license: by verdict: supports section: RESULTS > Final list of recommendations > Recommendations relating to diagnosis of underlying disorder (Box 3) quote: Autonomic dysfunction, especially manifesting as PoTS, occurs commonly post COVID-19.12 note: 'Found by winnow, kev and lev in p034, p028. Claude judged: supports.' - paper: pmid34192289 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. note: 'Found by winnow, kev and lev in p023, p001, p021. Claude judged: supports.' - paper: pmid34151246 cited: true text: full license: by verdict: supports section: Postural Orthostatic Tachycardia Syndrome and COVID-19 quote: This condition, called ”long COVID-19.” or ”post-acute sequelae of SARS-CoV-2 infection” is associated with multiple cardiopulmonary and neurologic symptoms, including severe chronic fatigue, palpitations, chest pain, breathlessness, and dysautonomia, features characteristic of postural tachycardia syndrome (POTS).184, 185, 186 POTS impacts heart rate, blood pressure, and cardiac function and can be caused by many factors, including viral infections.187 Although it remains unclear whether SARS-CoV-2 triggers POTS, emerging evidence indicates a close association between COVID-19 and POTS-like symptoms. note: 'Found by winnow, kev and lev in p052, p001. Claude judged: supports.' - paper: pmid33983522 cited: true text: full license: none verdict: supports section: 'Part II: Resolved Infection > Long COVID' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33983522. Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid33869099 cited: true text: abstract license: none verdict: supports section: Abstract > Learning Points quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33869099. Found by winnow, kev and lev in p001, p002. Claude judged: supports.' - paper: pmid33740207 cited: true text: full license: none verdict: supports section: Long-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33740207. Found by winnow, kev and lev in p004, p001, p002. Claude judged: supports.' - paper: pmid42788130 cited: true text: full license: by-nc verdict: partial section: Abstract > Case Presentation quote: Subsequent worsening of long COVID-19 symptoms alongside systemic dysautonomia emerged, including postural orthostatic tachycardia syndrome, orthostatic hypotension, and mast cell activation syndrome. note: 'Found by winnow, kev and lev in p002, p011, p015. Claude judged: partial.' - paper: pmid41713697 cited: true text: full license: by verdict: partial section: Discussion quote: Recent adult literature on long-COVID describes a POTS-like autonomic syndrome marked by COI, tachycardia, fatigue, pain, and cognitive symptoms, with some patients demonstrating delayed worsening months after the acute infection. note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid39043760 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: In this regard, Tsuchida and colleagues9 reported that treatment with a small dose of a beta-blocker was effective for ST-positive long COVID patients with POTS, suggesting that the manifestation of OI symptoms of POTS could be, at least in part, originated from the increase of HR in long COVID patients. note: 'Found by winnow, kev and lev in p004, p019, p022. Claude judged: partial.' - paper: pmid38900132 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38900132. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Not only does contracting SARS-CoV-2 infection confer the possibility of developing long COVID and subsequent development of POTS, but recipients of the SARS-CoV-2 vaccine have also been shown to develop POTS at a higher rate. note: 'Found by winnow, kev and lev in p006, p027, p029. Claude judged: partial.' - paper: pmid38469013 cited: true text: full license: by verdict: partial section: Discussion quote: Associations with multiple disorders have been identified, such as EDS described above and more recently COVID, and may provide insight into previously unrecognized etiologies, novel pathophysiology, and optimal management of patient symptoms [10-13]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid37822957 cited: true text: full license: by verdict: partial section: Abstract quote: All five patients who suffered a COVID-19 infection subsequently reported a pronounced and persistent exacerbation of POTS symptoms. note: 'Found by winnow, kev and lev in p019, p023, p003. Claude judged: partial.' - paper: pmid36981522 cited: true text: full license: by verdict: partial section: Abstract quote: He was found to have profound postural tachycardia syndrome, several ranges of motion restrictions, and mast cell activation syndrome. note: 'Found by winnow, kev and lev in p001, p023, p035. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: Abstract quote: Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. note: 'Found by winnow, kev and lev in p001, p004, p002. Claude judged: partial.' - paper: pmid36090156 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Although PASC and POTS might share common pathophysiological mechanisms and respond favorably to graded exercise training, few cases of PASC will likely fulfill a diagnosis of POTS. This initial case series shows the overlap between PASC, orthostatic intolerance, and POTS in recreational and competitive athletes, demonstrates the utility of performing autonomic function testing and CPET in making the diagnosis, and emphasizes the role of graded exercise training to treat this condition. note: 'Found by winnow, kev and lev in p014, p009. Claude judged: partial.' - paper: pmid35679657 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35679657. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35241011 cited: true text: full license: by verdict: partial section: Background quote: CFS/ME has been associated with several viruses, including the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV; 6), and has been recently garnering media attention as a post-acute consequence of SARS-CoV-2 infection. Below, we describe a dramatic case of POTS in a COVID-19 patient. note: 'Found by winnow, kev and lev in p005, p002, p004. Claude judged: partial.' - paper: pmid34541421 cited: true text: full license: by-nc-nd verdict: partial section: Results > Cardiovascular Complications quote: The combination of several commonly reported PASC symptoms (eg, dyspnea, palpitations, chest discomfort) in conjunction with orthostatic tachycardia may be a manifestation of postural tachycardia syndrome (POTS) (44). Several case studies have linked new diagnoses of POTS with prior COVID-19 infection (45, 46, 47), and additional surveillance will be necessary to characterize the frequency and persistence of these symptoms. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid33927679 cited: true text: full license: by verdict: partial section: Abstract quote: 'Conclusions: We present clinical features and results of autonomic testing in 6 patients with a history COVID-19 infection. While all patients reported typical features of orthostatic intolerance, fatigue, and activity intolerance, the results of autonomic testing were heterogenous, with orthostatic hypotension in 1 patient, excessive postural tachycardia typical of postural tachycardia syndrome in 4 patients, and postural hypertension in 3 patients.' note: 'Found by winnow, kev and lev in p003, p004, p006. Claude judged: partial.' - paper: pmid33786700 cited: true text: full license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33786700. Found by winnow, kev and lev in p020, p001, p004. Claude judged: partial.' - edge: - postinfectious_evidence - associated_with - pots papers: 74 evidence: - paper: pmid42512077 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Among proposed etiologies for POTS, Epstein–Barr virus and other pathogens have been identified as potential initiating events; frequently, patients report a history of mononucleosis prior to development of debilitating symptoms [24]. note: 'Found by winnow, kev and lev in p004, p001, p006. Claude judged: supports.' - paper: pmid41020219 cited: true text: full license: by verdict: supports section: 1 Introduction quote: This has led to POTS being a recognized complication of PASC. Clinicians with interests in dysautonomia have reported that up to 80% of PASC patients meet POTS diagnostic criteria (19–21). note: 'Found by winnow, kev and lev in p006, p025, p001. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Abstract > Background quote: As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. note: 'Found by winnow, kev and lev in p007, p001, p010. Claude judged: supports.' - paper: pmid39857750 cited: true text: full license: by verdict: supports section: 2. POTS, Long COVID and the CNS quote: Pre-pandemic, POTS was known to occur after a viral or bacterial infection in at least 40% of patients and was thought to be of heterogeneous and complex pathophysiology involving central and peripheral autonomic nervous system networks, small fiber neuropathy, cerebral hypoperfusion, mast cell hyperactivity and autoimmunity [9,10,11]. note: 'Found by winnow, kev and lev in p006, p001, p005. Claude judged: supports.' - paper: pmid39838139 cited: true text: full license: by verdict: supports section: Discussion quote: Hence POTS, a syndrome most commonly triggered by viral infections, also associated with cognitive difficulties and highly prevalent among patients with LC, becomes a suitable option to achieve this objective. note: 'Found by winnow, kev and lev in p005, p044. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > COVID-19 Infection and Post-viral Postural Orthostatic Tachycardia Syndrome quote: Even though an exact mechanism has not been identified, it is suggested that autoimmune responses to viral illness may trigger POTS, with up to 50% of POTS patients reporting a viral illness preceding their symptoms.[22] note: 'Found by winnow, kev and lev in p011, p031, p032. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 1. Introduction > 1.1. Definition and Clinical Features of POTS quote: Prior to diagnosis of POTS, patients often report illnesses involving viral infections in the upper respiratory or gastrointestinal systems. Identified viruses and bacteria associated with POTS include influenza, Epstein–Barr virus, and Borrelia burgdorferi [15]. note: 'Found by winnow, kev and lev in p009, p001, p011. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: The onset of POTS is frequently linked to triggers, such as long COVID-19, the human papillomavirus (HPV) vaccine, infections, or trauma, which can subsequently lead to immunological changes. note: 'Found by winnow, kev and lev in p014, p019. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Introduction quote: Over half of patients with POTS report a preceding infection (3). COVID-19 is increasingly recognized as a cause of POTS (4, 5), as well as other infections including Epstein Barr Virus (EBV) (6, 7). note: 'Found by winnow, kev and lev in p003, p013, p002. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Abstract quote: It is considered a relatively rare condition that affects approximately 0.2% of the general population, and it is estimated that between 500,000 to 1,000,000 individuals in the United States have the condition and recently has been linked to post-infectious (viral) etiologies. note: 'Found by winnow, kev and lev in p001, p002, p009. Claude judged: supports.' - paper: pmid37391116 cited: true text: full license: none verdict: supports section: Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p006, p015, p023. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Introduction > Clinical Features quote: Antecedent illness with viral infections of the upper respiratory and gastrointestinal tracts have been reported prior to onset of POTS.2,14,15 Offending organisms identified include Epstein-Barr virus, Influenza and Borrelia burgdorferi.16 note: 'Found by winnow, kev and lev in p010, p021, p013. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response.' note: 'Found by winnow, kev and lev in p003, p012, p001. Claude judged: supports.' - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Interestingly, POTS itself often develops following infectious diseases and, at least in some cases, may be associated with the production of autoantibodies against adrenergic and cholinergic receptors [35]. note: 'Found by winnow, kev and lev in p046, p035. Claude judged: supports.' - paper: pmid36339677 cited: true text: full license: by verdict: supports section: Introduction quote: POTS has largely been involved in post-viral symptomatology15–18, with 28–41% of POTS cases reported to be associated with viral infections19,20, suggesting post viral autoimmune activation is a possible pathophysiological mechanism16. note: 'Found by winnow, kev and lev in p001, p003, p007. Claude judged: supports.' - paper: pmid35381331 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p001, p014, p016. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 4. Postural Orthostatic Tachycardia Syndrome after COVID-19 quote: POTS is misdiagnosed in up to 75% of patients and viral infection is recognized as a trigger in up to 41% of cases [63]. note: 'Found by winnow, kev and lev in p008, p016, p017. Claude judged: supports.' - paper: pmid34192289 cited: true text: full license: by-nc-nd verdict: supports section: Cardiovascular manifestations of PACS > Postural Orthostatic Tachycardia Syndrome quote: POTS has previously been implicated in persistent post-viral symptomatology, with over 40% of POTS cases thought to be associated with viral infection, possibly triggered by induced autoimmunity or molecular mimicry. note: 'Found by winnow, kev and lev in p023, p001, p020. Claude judged: supports.' - paper: pmid33983522 cited: true text: full license: none verdict: supports section: 'Part II: Resolved Infection > Long COVID' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33983522. Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid33927679 cited: true text: full license: by verdict: supports section: Discussion quote: It is notable that 40–50% of POTS patients report an antecedent history of infection prior to symptom onset (13, 14). Various types of infections have been reported in association with the development of POTS, including Mycoplasma pneumonia (15), Epstein Barr virus (16, 17), Trypanosoma cruzii (18), and Borrelia burgdorferi (19, 20). note: 'Found by winnow, kev and lev in p006, p013. Claude judged: supports.' - paper: pmid33740207 cited: true text: full license: none verdict: supports section: Research opportunities to understand Long-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33740207. Found by winnow, kev and lev in p004, p007. Claude judged: supports.' - paper: pmid32848537 cited: true text: full license: by verdict: supports section: Discussion quote: A higher proportion of POTS patients reported symptoms of antecedent infections in our group of adolescents (60%) than previously described for adults (35%) (Kimpinski et al., 2012). note: 'Found by winnow, kev and lev in p039, p025, p037. Claude judged: supports.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: Antecedent infections were frequently reported in patients in POTS patients. note: 'Found by winnow, kev and lev in p001, p013. Claude judged: supports.' - paper: pmid19058765 cited: true text: full license: none verdict: supports section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021, p022, p035. Claude judged: supports.' - paper: pmid42746015 cited: true text: full license: by verdict: partial section: Introduction quote: PoTS is often triggered by viral infections, shows a female predominance (3), and can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS, ICD-10-GM G93.3, ICD-10-CM G93.32, ICD-11 8E49) (1). note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid42279051 cited: true text: full license: by verdict: partial section: 1. Introduction quote: A SARS-CoV-2 infection can result in long-term cardiovascular dysautonomia (CVD) characterized by abnormal autonomic reflexes upon standing, with a subset meeting diagnostic criteria for Postural Tachycardia Syndrome (PoTS) [1]. note: 'Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid41859298 cited: true text: full license: by-nc verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 as part of Long COVID and is a common comorbidity of ME/CFS.8,9 note: 'Found by winnow, kev and lev in p005, p007. Claude judged: partial.' - paper: pmid41300849 cited: true text: full license: by verdict: partial section: 1. Introduction quote: A central feature common to both PCS and CFS is orthostatic intolerance, frequently attributable to POTS. Reported prevalence of POTS in CFS ranges from 5.7% to 70%, largely depending on diagnostic criteria and study populations, while prevalence in PCS has been reported between 2% and 14% [7,8,9]. note: 'Found by winnow, kev and lev in p004, p007. Claude judged: partial.' - paper: pmid41146789 cited: true text: full license: by verdict: partial section: Review quote: The mechanism of POTS is not fully explained. Presently, it is considered that the etiology of POTS can be related to viral infections or other conditions, which involve an excessive activation of the immune system, α-receptor hyperactivity, and the presence of autoantibodies against receptor molecules on human cells [24-26]. note: 'Found by winnow, kev and lev in p018, p002, p011. Claude judged: partial.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Introduction > Long COVID quote: Consequently, many patients with Long COVID have POTS or OCADs (Blitshteyn and Whitelaw, 2021; Davenport et al., 2024), with nearly 70% of patients having a high autonomic symptom burden (Larsen et al., 2022). note: 'Found by winnow, kev and lev in p004, p013, p019. Claude judged: partial.' - paper: pmid41050528 cited: true text: full license: by-nc verdict: partial section: Case presentation quote: After a new COVID-19 infection in February 2021, he developed typical long COVID symptoms of dysautonomia, post-exertional malaise (PEM), and symptoms compatible with POTS. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid41038948 cited: true text: full license: by verdict: partial section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. It is estimated that up to 70% of patients with PASC have POTS, with clinicians worldwide seeing an increasing number of POTS patients4. note: 'Found by winnow, kev and lev in p003, p013. Claude judged: partial.' - paper: pmid40883051 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Background quote: Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing postacute COVID-19 syndrome, commonly referred to as long COVID. note: 'Found by winnow, kev and lev in p006, p001, p031. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Background quote: Prior to COVID-19, POTS was a relatively rare phenomenon, affecting otherwise healthy individuals following viral illness or trauma. note: 'Found by winnow, kev and lev in p005, p006, p009. Claude judged: partial.' - paper: pmid40660536 cited: true text: full license: by verdict: partial section: 3. Discussion quote: It frequently manifests during adolescence and can be triggered by immune stressors, such as viral infections, including COVID-19.[3,5,6] note: 'Found by winnow, kev and lev in p003, p015, p001. Claude judged: partial.' - paper: pmid40492086 cited: true text: full license: by-nd verdict: partial section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid40014480 cited: true text: full license: by verdict: partial section: Abstract > Background quote: Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance and is frequently observed in post‐COVID conditions. note: 'Found by winnow, kev and lev in p001, p005, p009. Claude judged: partial.' - paper: pmid39882369 cited: true text: full license: by verdict: partial section: Introduction quote: One of the most common syndromes of PASC bears striking resemblance to POTS, and in some evaluations of PASC patients up to 79% were noted to meet diagnostic criteria for POTS (12). note: 'Found by winnow, kev and lev in p001, p007. Claude judged: partial.' - paper: pmid39852767 cited: true text: full license: by verdict: partial section: 2. Case Presentation quote: However, an autoimmune basis of post-COVID POTS was evident given a positive ANA, comorbid SFN, and post-infectious onset of symptomatology. note: 'Found by winnow, kev and lev in p005, p007. Claude judged: partial.' - paper: pmid39775762 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: partial.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Abstract quote: SARS-CoV-2 infection (COVID-19) and the COVID-19 vaccine have been linked to the development of persistent symptoms, including orthostatic intolerance (OI) and postural orthostatic tachycardia syndrome (POTS), in both children and adults. note: 'Found by winnow, kev and lev in p031, p002, p008. Claude judged: partial.' - paper: pmid39554298 cited: true text: full license: by-nc verdict: partial section: DISCUSSION > Fatigue quote: POTS has been reported to occur after viral infections, and cases of POTS following COVID‐19 have also been reported. note: 'Found by winnow, kev and lev in p020, p019. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Case reports have described a new onset of autonomic dysfunction symptoms with features of POTS/inappropriate sinus tachycardia in the post-acute phase of COVID-19 infection [55,56]. The underlying cause of dysautonomia post-COVID-19 infection is not well understood. note: 'Found by winnow, kev and lev in p006, p027, p034. Claude judged: partial.' - paper: pmid38585346 cited: true text: full license: by verdict: partial section: Introduction quote: Autonomic dysfunction is a common consequence suffered by COVID long-haulers, manifesting in symptoms including headache, fatigue, orthostatic intolerance, tachycardia/palpitations, temperature intolerance, and more, reflecting the growing incidence of POTS pathophysiology in these patients (7). note: 'Found by winnow, kev and lev in p007, p002, p008. Claude judged: partial.' - paper: pmid38240001 cited: true text: full license: by verdict: partial section: INTRODUCTION quote: Factors contributing to the development of POTS after COVID‐19 infection are hypovolemia, neurotropism, inflammation, and autoimmunity. note: 'Found by winnow, kev and lev in p003, p009, p011. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: The syndrome is regarded to be the most prevalent cardiovascular dysautonomia and a primary phenotype/subsyndrome in the post-acute COVID-19 syndrome that can develop after SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37981644 cited: true text: full license: by verdict: partial section: Abstract quote: Post-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p002, p001, p003. Claude judged: partial.' - paper: pmid37822957 cited: true text: full license: by verdict: partial section: Abstract quote: Patients with POTS often experience an exacerbation of their symptoms associated with (viral) infections and often fear the same symptom aggravation after vaccination. note: 'Found by winnow, kev and lev in p023, p001, p003. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 4. Epidemiology quote: In a recent systematic review of cardiovascular autonomic dysfunction and COVID-19, POTS was the most frequent diagnosis in individuals with post–COVID-19 orthostatic complaints (37). note: 'Found by winnow, kev and lev in p001, p004, p014. Claude judged: partial.' - paper: pmid36938206 cited: true text: full license: by verdict: partial section: Abstract quote: The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. note: 'Found by winnow, kev and lev in p005, p001, p020. Claude judged: partial.' - paper: pmid36732397 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p001, p003, p004. Claude judged: partial.' - paper: pmid36729924 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36729924. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: Abstract quote: Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. note: 'Found by winnow, kev and lev in p004, p001, p006. Claude judged: partial.' - paper: pmid36703776 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: Here, we present a case report of severe dysautonomia following a COVID‐19 infection in a patient with pre‐existing poorly controlled type‐1 diabetes. This patient exhibited symptoms consistent with both postural orthostatic tachycardia syndrome (POTS), as well as orthostatic hypotension. note: 'Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - paper: pmid36518330 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Postural orthostatic tachycardia syndrome has recently been identified in ∼20% of patients with post-acute sequelae of COVID-19 (PASC). note: 'Found by winnow, kev and lev in p001, p002, p005. Claude judged: partial.' - paper: pmid35853576 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p010, p011. Claude judged: partial.' - paper: pmid35852546 cited: true text: full license: none verdict: partial section: Myalgien und POTS als Folge von Long-COVID? Versuch einer objektiven Bewertung > Spezifität. quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p012, p025, p030. Claude judged: partial.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: A range of diseases, including viral or bacterial infections, can cause POTS. Because an increasing number of patients who recovered from COVID-19 are now reporting POTS-like symptoms including brain fog, tachycardia and severe chronic fatigue, some experts believe coronavirus may be a trigger for POTS. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: “Post-COVID-19 Tachycardia Syndrome” quote: From a cardiovascular point of view, recent papers have highlighted an association between orthostatic intolerance (OI), including orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS), with long COVID (17–19). note: 'Found by winnow, kev and lev in p004, p008. Claude judged: partial.' - paper: pmid35269395 cited: true text: full license: by verdict: partial section: 1. Introduction quote: With associations of viral infections as a potential etiology of POTS and evidence that many COVID-19 long haulers are developing POTS, platelets may also play a significant role in the etiology or perpetuation of the disorder. note: 'Found by winnow, kev and lev in p003, p002. Claude judged: partial.' - paper: pmid35241011 cited: true text: full license: by verdict: partial section: Background quote: When dysautonomia manifests in the form of postural orthostatic tachycardia syndrome (POTS), patients report dizziness, lightheadedness, fatigue and tachycardia when standing from a sitting or lying position. Dysautonomia has been associated with several non-infectious conditions, from diabetes mellitus to Parkinson’s disease, as well as with viral infections, including, among others, HIV, hepatitis C, mumps, and Epstein-Barr virus [1]. note: 'Found by winnow, kev and lev in p005, p002, p004. Claude judged: partial.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: partial section: Abstract > Discussion quote: This novel case series describes the development of PTS in the context of COVID-19 infection. note: 'Found by winnow, kev and lev in p012, p002, p003. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Abstract quote: A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. note: 'Found by winnow, kev and lev in p002, p001, p003. Claude judged: partial.' - paper: pmid34541421 cited: true text: full license: by-nc-nd verdict: partial section: Results > Cardiovascular Complications quote: Several case studies have linked new diagnoses of POTS with prior COVID-19 infection (45, 46, 47), and additional surveillance will be necessary to characterize the frequency and persistence of these symptoms. Whether and how COVID-19 infection directly causes POTS is still unknown. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid34151246 cited: true text: full license: by verdict: partial section: Postural Orthostatic Tachycardia Syndrome and COVID-19 quote: POTS impacts heart rate, blood pressure, and cardiac function and can be caused by many factors, including viral infections.187 Although it remains unclear whether SARS-CoV-2 triggers POTS, emerging evidence indicates a close association between COVID-19 and POTS-like symptoms. note: 'Found by winnow, kev and lev in p052. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Epidemiology & natural history quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p001, p008. Claude judged: partial.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: A significant number of our patients have described Epstein–Barr virus infections and gastrointestinal pain that could be related to an enteric viral infection preceding the onset of symptoms and ultimately the development of POTS and its diagnosis. note: 'Found by winnow, kev and lev in p002, p025. Claude judged: partial.' - paper: pmid31001074 cited: true text: full license: by verdict: partial section: Discussion > The Role of Immune System in POTS quote: Its onset is occasionally preceded by or associated with a viral-like illness or post vaccination which leads to the suspicion that autoimmunity may have an important role in these patients (Li et al., 2014; Brinth et al., 2015). note: 'Found by winnow, kev and lev in p027, p005. Claude judged: partial.' - paper: pmid28738696 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28738696. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid28674681 cited: true text: full license: by verdict: partial section: Etiology and Pathophysiology > Pathophysiological Basis for Symptoms > Circulatory Abnormalities quote: More work is needed to define the causes of NMH and POTS. Both can follow infectious illnesses, and themselves can be secondary to autoimmune phenomena. note: 'Found by winnow, kev and lev in p035. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Autoimmune/Autoantibodies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p031. Claude judged: partial.' - paper: pmid25087056 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25087056. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid24830783 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24830783. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - long_covid - associated_with - postinfectious_evidence papers: 63 evidence: - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 as part of Long COVID and is a common comorbidity of ME/CFS.8,9 note: 'Found by winnow, kev and lev in p005, p007. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Abstract quote: It is considered a relatively rare condition that affects approximately 0.2% of the general population, and it is estimated that between 500,000 to 1,000,000 individuals in the United States have the condition and recently has been linked to post-infectious (viral) etiologies. We present a case of a 53-year-old woman who was diagnosed with POTS following extensive autoimmune workup, who was also status post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. note: 'Found by winnow, kev and lev in p001, p002, p004. Claude judged: supports.' - paper: pmid37391116 cited: true text: full license: none verdict: supports section: Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p006, p007, p015. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Autonomic dysfunction in acute and Long Covid > Long Covid autonomic dysfunction quote: There have been many reports of clinical cases and series describing POTS, inappropriate sinus tachycardia and orthostatic hypotension (all impairments of the cardiovascular autonomic nervous system) following Covid infection [33–42]. note: 'Found by winnow, kev and lev in p008, p013. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Introduction and background quote: With the reporting of an increasing number of cases, POTS is gaining recognition in patients with COVID-19 in the post-infectious stage [8]. note: 'Found by winnow, kev and lev in p012, p001, p003. Claude judged: supports.' - paper: pmid35381331 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35381331. Found by winnow, kev and lev in p001, p014, p016. Claude judged: supports.' - paper: pmid35241011 cited: true text: full license: by verdict: supports section: Abstract > Background quote: The emergence of dysautonomia as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; or COVID-19) is becoming more prevalent. We have seen evidence in several post-COVID patients and in the literature of varying degrees of autonomic dysfunction. note: 'Found by winnow, kev and lev in p005, p001, p002. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Abstract > Background quote: Postural tachycardia syndrome (PTS) is a novel identified sequela of COVID-19 infection. This observational study describes clinical presentation, testing, and treatment response in seven patients diagnosed with PTS following COVID-19 infection. note: 'Found by winnow, kev and lev in p012, p001, p002. Claude judged: supports.' - paper: pmid34607799 cited: true text: full license: by verdict: supports section: RESULTS > Final list of recommendations > Recommendations relating to diagnosis of underlying disorder (Box 3) quote: Autonomic dysfunction, especially manifesting as PoTS, occurs commonly post COVID-19.12 note: 'Found by winnow, kev and lev in p028, p034. Claude judged: supports.' - paper: pmid33927679 cited: true text: full license: by verdict: supports section: Introduction quote: That dysautonomia should occur in conjunction with or following COVID-19 should be expected, given a reported prevalence of dysautonomia in 50% of severe acute respiratory syndrome (SARS) patients studied in the 2002 SARS epidemic (4), and that the most prevalent, primary autonomic disorder, postural tachycardia syndrome (POTS), is commonly associated with antecedent or concomitant infection. note: 'Found by winnow, kev and lev in p003, p006. Claude judged: supports.' - paper: pmid33786700 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33786700. Found by winnow, kev and lev in p020, p004, p006. Claude judged: supports.' - paper: pmid42512077 cited: true text: full license: by verdict: partial section: 2. Materials and Methods > 2.2. Patients quote: Patients in Group 2 were diagnosed prior to the pandemic and patients in Group 4 required symptom onset following a documented positive SARS-CoV-2 screening test. note: 'Found by winnow, kev and lev in p004, p001, p009. Claude judged: partial.' - paper: pmid42279051 cited: true text: full license: by verdict: partial section: 1. Introduction quote: A SARS-CoV-2 infection can result in long-term cardiovascular dysautonomia (CVD) characterized by abnormal autonomic reflexes upon standing, with a subset meeting diagnostic criteria for Postural Tachycardia Syndrome (PoTS) [1]. CVD develops during or following an acute COVID-19 infection, persisting beyond three months to years after exclusion of alternative diagnoses [2]. note: 'Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid41713697 cited: true text: full license: by verdict: partial section: Discussion quote: Recent adult literature on long-COVID describes a POTS-like autonomic syndrome marked by COI, tachycardia, fatigue, pain, and cognitive symptoms, with some patients demonstrating delayed worsening months after the acute infection. Although these data are largely derived from adult cohorts, we are increasingly seeing similar postinfectious autonomic symptom patterns in pediatric patients. note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid41282714 cited: true text: full license: by verdict: partial section: Discussion quote: A similar trajectory was observed for patients with POTS, suggesting that post-viral autonomic dysfunction may also act as a diagnostic trigger for hEDS. note: 'Found by winnow, kev and lev in p011, p046, p001. Claude judged: partial.' - paper: pmid41146789 cited: true text: full license: by verdict: partial section: Review quote: The mechanism of POTS is not fully explained. Presently, it is considered that the etiology of POTS can be related to viral infections or other conditions, which involve an excessive activation of the immune system, α-receptor hyperactivity, and the presence of autoantibodies against receptor molecules on human cells [24-26]. note: 'Found by winnow, kev and lev in p018, p002, p011. Claude judged: partial.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Abstract quote: The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. note: 'Found by winnow, kev and lev in p001, p013, p019. Claude judged: partial.' - paper: pmid41050528 cited: true text: full license: by-nc verdict: partial section: Case presentation quote: After a new COVID-19 infection in February 2021, he developed typical long COVID symptoms of dysautonomia, post-exertional malaise (PEM), and symptoms compatible with POTS. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid41038948 cited: true text: full license: by verdict: partial section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. It is estimated that up to 70% of patients with PASC have POTS, with clinicians worldwide seeing an increasing number of POTS patients4. note: 'Found by winnow, kev and lev in p003, p013. Claude judged: partial.' - paper: pmid41020219 cited: true text: full license: by verdict: partial section: Abstract > Introduction quote: As many as 80% of coronavirus disease 2019 (COVID-19) long-hauler patients meet the diagnostic criteria for POTS, highlighting awareness of this debilitating multisystem disorder. The etiology of POTS has not been entirely defined, but researchers have speculated that an immunological stressor such as a viral infection might be an initiating event. note: 'Found by winnow, kev and lev in p006, p001, p004. Claude judged: partial.' - paper: pmid40883051 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: Postacute COVID-19 syndrome, or long COVID, is estimated to affect 10 to 20% of people infected by SARS-COV-2.1, 2, 3 Postural orthostatic tachycardia syndrome (POTS) has emerged as a significant cardiovascular phenotype among individuals experiencing long COVID.4 note: 'Found by winnow, kev and lev in p001, p003, p006. Claude judged: partial.' - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Introduction > Background quote: Prior to COVID-19, POTS was a relatively rare phenomenon, affecting otherwise healthy individuals following viral illness or trauma. note: 'Found by winnow, kev and lev in p005, p009, p025. Claude judged: partial.' - paper: pmid40660536 cited: true text: full license: by verdict: partial section: 3. Discussion quote: It frequently manifests during adolescence and can be triggered by immune stressors, such as viral infections, including COVID-19.[3,5,6] note: 'Found by winnow, kev and lev in p003, p015, p001. Claude judged: partial.' - paper: pmid40492086 cited: true text: full license: by-nd verdict: partial section: Introduction quote: This syndrome, characterized by an abnormal increase in heart rate upon standing without a corresponding drop in blood pressure, has gained increasing recognition, particularly due to its association with long COVID/post-acute sequelae of SARS-CoV-2 infection (PASC)2,3. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid40014480 cited: true text: full license: by verdict: partial section: Abstract > Background quote: Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance and is frequently observed in post‐COVID conditions. note: 'Found by winnow, kev and lev in p001, p005, p006. Claude judged: partial.' - paper: pmid39884840 cited: true text: full license: by-nc verdict: partial section: Background quote: The prevalence is thought to have increased since as autonomic dysfunction, including POTS, is one of the most reported post-acute sequelae of COVID-19, affecting up to half of those with long COVID (Larsen et al., 2022; Mallick et al., 2023). note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid39882369 cited: true text: full license: by verdict: partial section: Introduction quote: In the wake of the COVID-19 pandemic, a significant proportion of survivors were noted to have symptoms continuing or developing after their acute infection, termed Post Acute Sequelae of COVID (PASC) (11). note: 'Found by winnow, kev and lev in p007, p001. Claude judged: partial.' - paper: pmid39875497 cited: true text: full license: by verdict: partial section: Discussion quote: Our findings are similar to those reported in the PASC population although our patients with POTS had an average symptom duration of 6 years prior to their brain SPECT while those with PASC in our cohort were studied at almost 1 year since their acute COVID-19 infection. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid39857750 cited: true text: full license: by verdict: partial section: Abstract quote: POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p006, p001. Claude judged: partial.' - paper: pmid39852767 cited: true text: full license: by verdict: partial section: 2. Case Presentation quote: A woman in her mid-forties with a history of episodic migraine and seasonal allergies developed rapid heart rate, dizziness, body pain, fatigue, exercise intolerance, and brain fog after experiencing a mild SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p005, p001, p004. Claude judged: partial.' - paper: pmid39775762 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: partial.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Abstract quote: This study highlights the growing incidence of POTS and other forms of OI in pediatric patients following COVID-19 infection and vaccination, supporting the link between COVID-19 and autonomic dysfunction in children. note: 'Found by winnow, kev and lev in p031, p008, p030. Claude judged: partial.' - paper: pmid39523946 cited: true text: full license: by-nc-nd verdict: partial section: 'Abstract > BACKGROUND:' quote: Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. note: 'Found by winnow, kev and lev in p003, p001, p002. Claude judged: partial.' - paper: pmid39207648 cited: true text: full license: by verdict: partial section: Introduction > Symptoms of PASC quote: Recently, POTS has been linked to PASC [20, 26, 27]. note: 'Found by winnow, kev and lev in p030, p006. Claude judged: partial.' - paper: pmid38585346 cited: true text: full license: by verdict: partial section: Introduction quote: Autonomic dysfunction is a common consequence suffered by COVID long-haulers, manifesting in symptoms including headache, fatigue, orthostatic intolerance, tachycardia/palpitations, temperature intolerance, and more, reflecting the growing incidence of POTS pathophysiology in these patients (7). note: 'Found by winnow, kev and lev in p007, p002, p024. Claude judged: partial.' - paper: pmid38510743 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: The long Covid syndrome is characterized with orthostatic hypotension, impaired cardiac and cerebral perfusion, postural orthostatic tachycardia syndrome (POTS), syncope, chest pain, dyspnea, palpitation, chronic fatigue syndrome, ‘brain fog’, memory, cognitive and sleep difficulties, depression and anxiety. note: 'Found by winnow, kev and lev in p001, p028. Claude judged: partial.' - paper: pmid38392604 cited: true text: full license: by verdict: partial section: 1. Introduction > Orthostasis, Orthostatic Intolerance, and POTS quote: Although well known in other contexts for at least three decades [6,7] (see Table 1), with at least 500,000 cases in the USA alone [8,9,10], mostly in women (5:1) [5,9,11,12,13,14], POTS has emerged as a frequent symptom of both acute [15] and long COVID (e.g., [16,17,18,19,20,21] as part of the wider cardiovascular dysautonomia spectrum; see Table 1). note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid38240001 cited: true text: full license: by verdict: partial section: Abstract > Results quote: 'Thirty‐two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow‐up period was 159 days, and the interval between COVID‐19 onset and initial hospital attendance was 97 days.' note: 'Found by winnow, kev and lev in p011, p003, p004. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: There is strong evidence that SARS-CoV-2 may trigger POTS in patients with prolonged COVID-19 syndrome. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37981644 cited: true text: full license: by verdict: partial section: Introduction quote: This novel condition is referred to as post-acute COVID-19 syndrome (PACS)1 and is defined as persisting symptoms > 12 weeks after contracting an acute SARS-CoV-2 infection2. note: 'Found by winnow, kev and lev in p002, p001, p005. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 4. Epidemiology quote: The timing of POTS symptom onset was concurrent with usual acute COVID-19 symptoms, but it may occur months after infection (39, 40). note: 'Found by winnow, kev and lev in p001, p004, p014. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports quote: Contemporary literature indicates potential links between viral infections and vaccines (particularly HPV) with the development of POTS.14,35,36 The earliest reports of a POTS-like syndrome in the aftermath of COVID-19 infection emerged in March 2020.37 note: 'Found by winnow, kev and lev in p021, p013, p020. Claude judged: partial.' - paper: pmid36938206 cited: true text: full license: by verdict: partial section: Abstract quote: The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. note: 'Found by winnow, kev and lev in p005, p001, p008. Claude judged: partial.' - paper: pmid36732397 cited: true text: full license: none verdict: partial section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p001, p003. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: INTRODUCTION quote: Because viral infection can host various chronic neurological conditions, such as Guillain-Barre syndrome, POTS can possibly occur as a post-COVID-19 autonomic nerve involvement. note: 'Found by winnow, kev and lev in p004, p001, p002. Claude judged: partial.' - paper: pmid36639608 cited: true text: full license: none verdict: partial section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p022, p024, p025. Claude judged: partial.' - paper: pmid36611357 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Interestingly, POTS itself often develops following infectious diseases and, at least in some cases, may be associated with the production of autoantibodies against adrenergic and cholinergic receptors [35]. note: 'Found by winnow, kev and lev in p046, p003, p035. Claude judged: partial.' - paper: pmid36339677 cited: true text: full license: by verdict: partial section: Introduction quote: POTS has largely been involved in post-viral symptomatology15–18, with 28–41% of POTS cases reported to be associated with viral infections19,20, suggesting post viral autoimmune activation is a possible pathophysiological mechanism16. With an increasing number of patients being described with a wide variety of symptoms, particularly those implicated in autonomic dysfunction, long after their acute COVID-19 infectious period, we aimed to review the available literature on post COVID-19 POTS cases. note: 'Found by winnow, kev and lev in p001, p003, p007. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Selected Etiology: Post-COVID-19 > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p107, p111, p112. Claude judged: partial.' - paper: pmid35891154 cited: true text: full license: by verdict: partial section: 3. Discussion quote: Post-COVID-19-virus-associated POTS has been reported and seems to be far more prevalent than post-COVID-19-vaccine-associated POTS [8,9,15,25,32,33,34]. Despite the handful of cases describing new-onset POTS after the COVID-19 vaccine, the vaccine has demonstrated significant protection against SARS-CoV-2 infection and reduces risk of developing Long-COVID or post-infectious POTS [35]. note: 'Found by winnow, kev and lev in p014, p015, p017. Claude judged: partial.' - paper: pmid35853576 cited: true text: full license: none verdict: partial section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p001, p010, p011. Claude judged: partial.' - paper: pmid35852546 cited: true text: full license: none verdict: partial section: 'Neuromuskuläre Erkrankungen nach COVID-19: Was ist gesichert? > Autonome Dysfunktion' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35852546. Found by winnow, kev and lev in p012, p030. Claude judged: partial.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: A range of diseases, including viral or bacterial infections, can cause POTS. Because an increasing number of patients who recovered from COVID-19 are now reporting POTS-like symptoms including brain fog, tachycardia and severe chronic fatigue, some experts believe coronavirus may be a trigger for POTS. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: “Post-COVID-19 Tachycardia Syndrome” quote: Numerous reports have described the development of POTS as part of long COVID (19, 25–27) although the aetiology remains debated. note: 'Found by winnow, kev and lev in p004, p008. Claude judged: partial.' - paper: pmid35269395 cited: true text: full license: by verdict: partial section: 1. Introduction quote: With associations of viral infections as a potential etiology of POTS and evidence that many COVID-19 long haulers are developing POTS, platelets may also play a significant role in the etiology or perpetuation of the disorder. note: 'Found by winnow, kev and lev in p003, p002. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 3. COVID-19 Infection and Dysautonomia quote: A growing body of evidence links PASC to CVAD, with a number of reports suggesting the possibility of previously infected COVID-19 patients experiencing symptoms suggestive of POTS [10,13,16,43,44,45,46]. This is also consistent with previous evidence hinting at the presence of CVAD in SARS survivors during the 2003 epidemic [47]. note: 'Found by winnow, kev and lev in p008, p003, p013. Claude judged: partial.' - paper: pmid34729276 cited: true text: full license: by verdict: partial section: Abstract quote: A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: partial.' - paper: pmid34541421 cited: true text: full license: by-nc-nd verdict: partial section: Results > Cardiovascular Complications quote: Several case studies have linked new diagnoses of POTS with prior COVID-19 infection (45, 46, 47), and additional surveillance will be necessary to characterize the frequency and persistence of these symptoms. Whether and how COVID-19 infection directly causes POTS is still unknown. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid34192289 cited: true text: full license: by-nc-nd verdict: partial section: Cardiovascular manifestations of PACS > Postural Orthostatic Tachycardia Syndrome quote: In two other case series with a total of 10 patients diagnosed with POTS, the timing of POTS symptom onset was most often concurrent with usual acute COVID-19 symptoms but cases of POTS occurring up to months after initial infection were seen [40,41]. note: 'Found by winnow, kev and lev in p023, p021, p022. Claude judged: partial.' - paper: pmid34151246 cited: true text: full license: by verdict: partial section: Postural Orthostatic Tachycardia Syndrome and COVID-19 quote: POTS impacts heart rate, blood pressure, and cardiac function and can be caused by many factors, including viral infections.187 Although it remains unclear whether SARS-CoV-2 triggers POTS, emerging evidence indicates a close association between COVID-19 and POTS-like symptoms. note: 'Found by winnow, kev and lev in p052. Claude judged: partial.' - paper: pmid33996867 cited: true text: full license: by verdict: partial section: Abstract quote: We describe three adolescent and young adult patients who had confirmed or probable COVID-19 infections early on during the pandemic and were referred for evaluation to the Chronic Fatigue Clinic at the Johns Hopkins Children's Center. All patients reported orthostatic intolerance symptoms within the first 2 weeks of illness, and 10-min passive standing tests were consistent with postural tachycardia syndrome. note: 'Found by winnow, kev and lev in p002, p004, p006. Claude judged: partial.' - paper: pmid33869099 cited: true text: abstract license: none verdict: partial section: Abstract > Unlabelled quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33869099. Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - paper: pmid33740207 cited: true text: full license: none verdict: partial section: Research opportunities to understand Long-COVID POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33740207. Found by winnow, kev and lev in p004, p007. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - pots papers: 59 evidence: - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Discussion quote: 'Moreover, POTS is also associated with a higher prevalence of atopic conditions and autoimmune disorders compared to the general population: Asthma (20.3% (95% CI 19.1–21.5) in POTS vs. 3.3% (95% CI 2.9–3.8) in the general population [32]), Hashimoto''s disease (8.3% (95% CI 4.1–16.0) vs. 7.5% (95% CI 5.7–9.6) [33]), Raynaud''s syndrome (15.5% (95% CI 14.4–16.7) vs. 4.85% (95% CI 2.1–8.7) [34]), and Sjögren''s syndrome (4.7% (95% CI 1.7–12.2) versus 0.06% (95% CI 0.04–0.08) [35]).' note: 'Found by winnow, kev and lev in p030, p036. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: The term "secondary POTS" is often reserved for the subtype associated with a chronic disease or autoimmune syndrome. About 20% of patients with an autoimmune disease have POTS [18]. note: 'Found by winnow, kev and lev in p084, p072, p099. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Autoimmunity > Comorbidity with undifferentiated connective tissue disease quote: POTS and OCADs are commonly comorbid with other autoimmune disorders, with the most common being Hashimoto’s thyroiditis (Blitshteyn, 2015). Their association with Sjögren’s syndrome, antiphospholipid syndrome, and celiac disease has also been reported (Schofield et al., 2014; Penny et al., 2016; Mannan and Pain, 2023). note: 'Found by winnow, kev and lev in p015, p001, p003. Claude judged: supports.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Results quote: AR-modulating autoantibody activity was also higher in patients with POTS vs those without and directly correlated with heart rate changes. note: 'Found by winnow, kev and lev in p025, p004, p005. Claude judged: supports.' - paper: pmid39527936 cited: true text: full license: by-nc verdict: supports section: Introduction quote: While none of these conditions is currently understood to be autoimmune in nature, there appears to be a higher prevalence of autoimmunity in individuals with POTS and those with hEDS relative to the general population. In a large cohort of patients with POTS, 16% had one or more autoimmune diseases, including Hashimoto’s thyroiditis (6%), celiac disease (3%), rheumatoid arthritis (RA) (2%), and systemic lupus erythematosus (SLE) (2%), all greater than the prevalence in the general population [10]. note: 'Found by winnow, kev and lev in p007, p019, p021. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: POTS has a higher prevalence of autoimmune markers and co-morbid autoimmune disorders, e.g., Hashimoto’s thyroiditis and rheumatoid arthritis [42]. note: 'Found by winnow, kev and lev in p014, p003, p015. Claude judged: supports.' - paper: pmid38900132 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38900132. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.5. Antiphospholipid and Antinuclear Autoantibodies quote: A higher prevalence of ANA AAbs and aPL AAbs were found in patients with POTS compared to the general population. The presence of Hashimoto’s thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis was found to be statistically significantly higher in POTS patients compared to the general population [59]. note: 'Found by winnow, kev and lev in p021, p030, p001. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Autoimmunity has been proposed as a possible etiological mechanism in POTS, with high prevalence of diverse antibodies in previous reports (Fedorowski, 2019). Moreover, increased prevalence of co-morbid systemic autoimmune rheumatic disorders have been reported in POTS (Mannan and Pain, 2023), but causative autoantibodies have not been found so far (Vernino and Stiles, 2018). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid38311655 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38311655. Found by winnow, kev and lev in p002, p003. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: supports section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010, p018, p019. Claude judged: supports.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: According to Gunning et al.,110 POTS is associated with increased G-protein coupled receptor autoantibodies. Other proposed mechanisms included those against ACE-2 and muscarinic receptors.111 note: 'Found by winnow, kev and lev in p061. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Auto-antibodies in POTS and Long Covid—significance and implications for future study quote: 'The association between POTS and autoantibodies is well recognized: auto-antibodies to the α and β receptors on GPCR antibodies, ganglionic acetylcholine receptor antibodies, angiotensin II receptor antibodies and antibodies to structural cardiac proteins have been identified in POTS [14, 27, 75–78].' note: 'Found by winnow, kev and lev in p009, p020, p001. Claude judged: supports.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: A review of autoimmunity in POTS by Ref. [5] found that “patients with POTS have a higher than expected frequency of defined autoimmune disorders such as multiple sclerosis, lupus, Sjögren syndrome or celiac disease”. note: 'Found by winnow, kev and lev in p003, p022, p074. Claude judged: supports.' - paper: pmid36639608 cited: true text: full license: none verdict: supports section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid35269395 cited: true text: full license: by verdict: supports section: Abstract quote: The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. note: 'Found by winnow, kev and lev in p001, p002, p012. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Antibodies and immunology of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p022, p009. Claude judged: supports.' - paper: pmid34055446 cited: true text: full license: by verdict: supports section: 3. Discussion quote: A pathogenesis of POTS includes an autoimmune basis with a high prevalence of positive ANA and comorbid autoimmune disorders [3]. Additionally, there has been an association between POTS syndrome and antiphospholipid antibody syndrome [4]. note: 'Found by winnow, kev and lev in p010, p011, p014. Claude judged: supports.' - paper: pmid33621398 cited: true text: full license: by verdict: supports section: Introduction quote: Several groups previously confirmed these autonomic manifestations and identified complications in AGID or autoimmune POTS patients who were seropositive for the gAChR Abs. note: 'Found by winnow, kev and lev in p024, p005, p016. Claude judged: supports.' - paper: pmid33562074 cited: true text: full license: by verdict: supports section: Abstract quote: A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. note: 'Found by winnow, kev and lev in p033, p001, p002. Claude judged: supports.' - paper: pmid32983103 cited: true text: full license: by verdict: supports section: Pediatric VVS and/or POTS Comorbid With Allergic Diseases > Pathogenesis > Autoimmunity quote: On the other hand, increasing evidence has shown that POTS is related to autoimmunity (57). Blitshteyn found that one quarter of the patients had antinuclear antibodies (ANA), almost one third of the patients had autoimmune markers, and one fifth of the patients had coexisting autoimmune diseases (58). note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots > Autoimmune Dysfunction quote: Autoimmune disturbance has been considered as one of the mechanisms involved in POTS due to frequent findings of autoantibodies in patients (11, 86, 87). note: 'Found by winnow, kev and lev in p019. Claude judged: supports.' - paper: pmid32750291 cited: true text: full license: by-nc-nd verdict: supports section: Discussion > Orthostatic Symptoms in Relation to Receptor Activity quote: The same study indicated that 89% of patients with POTS had autoantibodies against ADRA1 whereas antibodies against other adrenergic and muscarinic antibodies were less prevalent. note: 'Found by winnow, kev and lev in p033, p001, p016. Claude judged: supports.' - paper: pmid32743496 cited: true text: full license: by verdict: supports section: Abstract > Background quote: Activating autoantibodies (AAb) to adrenergic receptors (AR) have previously been reported in patients with postural tachycardia syndrome (POTS). These AAb may contribute to a final common pathway for overlapping disease processes, reflecting a possible autoimmune contribution to POTS pathophysiology. note: 'Found by winnow, kev and lev in p027, p001, p003. Claude judged: supports.' - paper: pmid31547749 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Antiganglionic acetylcholine receptor antibodies were found to be variably present in POTS patients.11, 13 Our group first reported the presence of activating autoantibodies (AAb) to the α1‐adrenergic (α1AR) and β1/2‐adrenergic receptors (β1/2AR) in a significant proportion of patients with POTS in 2014.14 note: 'Found by winnow, kev and lev in p007, p001, p003. Claude judged: supports.' - paper: pmid31495251 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: Our observations provide further evidence that, in most cases, POTS patients have at least 1 elevated G‐protein coupled adrenergic autoantibody and, in some instances, both adrenergic and muscarinic autoantibodies, supporting the hypothesis that POTS may be an autoimmune disorder. note: 'Found by winnow, kev and lev in p002, p001, p003. Claude judged: supports.' - paper: pmid31139694 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: All patients with prominent POTS had autoantibodies to β2AR, which suggests antibody‐mediated pathophysiology in these patients. note: 'Found by winnow, kev and lev in p001, p011, p014. Claude judged: supports.' - paper: pmid31001074 cited: true text: full license: by verdict: supports section: Discussion > The Role of Immune System in POTS quote: Studies performed recently indicate that patients with POTS have higher prevalence of autoimmune markers and co-morbid autoimmune disorders compared with the general population (Blitshteyn, 2015). Accordingly, nearly one fourth of patients with POTS have positive ANA and one in three have some type of autoimmune markers (Blitshteyn, 2015). note: 'Found by winnow, kev and lev in p027, p001, p003. Claude judged: supports.' - paper: pmid29909990 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29909990. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: A study of 100 consecutive patients with POTS found that 31% of patients had 1 or more antibody markers and 20% had comorbid autoimmune disorders such as Hashimoto's thyroiditis, rheumatoid arthritis, or systemic lupus erythematosus.35 note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: Moreover, autoimmune markers and comorbid autoimmune diseases were also frequent in seropositive POTS patients. Anti‐gAChR antibodies were detectable in significant number of patients with POTS, and POTS entailed the element of autoimmune basis. note: 'Found by winnow, kev and lev in p001, p003, p015. Claude judged: supports.' - paper: pmid29618472 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Methods and Results quote: All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1‐adrenergic receptor. note: 'Found by winnow, kev and lev in p005, p001, p002. Claude judged: supports.' - paper: pmid28738696 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28738696. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid27702852 cited: true text: full license: by-nc verdict: supports section: Discussion quote: It seems apparent that the high percentage of POTS subjects examined by our group present with an apparent autoimmune diathesis that supports the concept that these autoantibodies play important role in the pathophysiology of this entity. note: 'Found by winnow, kev and lev in p018, p031, p002. Claude judged: supports.' - paper: pmid26038344 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26038344. Found by winnow, kev and lev in p003, p001, p002. Claude judged: supports.' - paper: pmid25087056 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25087056. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid23002038 cited: true text: full license: none verdict: supports section: Abstract > Conclusions and clinical relevance quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23002038. Found by winnow, kev and lev in p004, p019, p001. Claude judged: supports.' - paper: pmid41859298 cited: true text: full license: by-nc verdict: partial section: Long COVID quote: Other major pathophysiologic mechanisms of Long COVID include autoimmune, inflammatory and immune dysregulations, which are similar to the pathophysiology of POTS. Elevated serum autoimmune and inflammatory markers have been found in patents with POTS and in patients with Long COVID. note: 'Found by winnow, kev and lev in p007, p012. Claude judged: partial.' - paper: pmid41146789 cited: true text: full license: by verdict: partial section: Review quote: Presently, it is considered that the etiology of POTS can be related to viral infections or other conditions, which involve an excessive activation of the immune system, α-receptor hyperactivity, and the presence of autoantibodies against receptor molecules on human cells [24-26]. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid40432440 cited: true text: full license: by verdict: partial section: Results quote: Significantly higher levels of angiotensin II type 1 receptor (AT1R) autoantibodies were in the POTS group compared with controls (0.67± 0.35 vs. 0.38±0.32, p=0.008). note: 'Found by winnow, kev and lev in p001, p006, p023. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Patients with autoimmune-related POTS may also present with autoimmune disorders as comorbidities. The onset of POTS in these patients may be related to autoantibodies against ganglionic acetylcholine receptors and α1-adrenergic receptors, although no definitive pathways have been identified. note: 'Found by winnow, kev and lev in p011, p032. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response. Few of the patients were detected to have autoantibodies to adrenergic, acetylcholine, and angiotensin II receptors [12,15].' note: 'Found by winnow, kev and lev in p012, p003, p051. Claude judged: partial.' - paper: pmid36908200 cited: true text: full license: none verdict: partial section: 'Discussion: > Interpretation: > Comorbid Autoimmune Disorders:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36908200. Found by winnow, kev and lev in p015, p020, p041. Claude judged: partial.' - paper: pmid36611357 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Interestingly, POTS itself often develops following infectious diseases and, at least in some cases, may be associated with the production of autoantibodies against adrenergic and cholinergic receptors [35]. note: 'Found by winnow, kev and lev in p046. Claude judged: partial.' - paper: pmid36509178 cited: true text: full license: none verdict: partial section: Discussion > Hospitalization status quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36509178. Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Discussion quote: Although the exact mechanism of vaccine-induced POTS is not clear, the autoimmune pathophysiology might be a key component [13-15]. note: 'Found by winnow, kev and lev in p001, p004, p014. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Selected Etiology: Autoimmune > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p066, p062, p067. Claude judged: partial.' - paper: pmid35870086 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p005, p006. Claude judged: partial.' - paper: pmid35062788 cited: true text: full license: by verdict: partial section: 6. Discussion quote: Furthermore, with cohorts of POTS patients recently being found to have adrenergic or muscarinic autoantibodies [36,77,78], and given known MC surface expression of adrenergic and muscarinic receptors which are active in the regulation of MC function [36], it even becomes possible, at least in theory, to drive MC activation (and thus at least those types of POTS underpinned by MCAS) via such autoantibodies as well. note: 'Found by winnow, kev and lev in p020. Claude judged: partial.' - paper: pmid34993884 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34993884. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34895744 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34895744. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: partial section: Discussion quote: It can be speculated from previous studies that autonomic nervous dysfunction in patients diagnosed with comorbidities of POTS and chronic fatigue syndrome may be related to autoantibodies against G-protein-coupled receptors and small fiber neuropathy.41–43 However, at present, the exact role of these antibodies is not fully understood. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid34484936 cited: true text: abstract license: none verdict: partial section: Abstract > Objective quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34484936. Found by winnow, kev and lev in p001, p003. Claude judged: partial.' - paper: pmid34471867 cited: true text: full license: by verdict: partial section: Discussion quote: In this case the diagnostic work-up of PoTS led to the diagnosis of autoimmune-mediated neuropathic PoTS as a crossroad of PoTS, SFN and autoimmunity. note: 'Found by winnow, kev and lev in p023, p001, p004. Claude judged: partial.' - paper: pmid33886735 cited: true text: full license: by verdict: partial section: Fisiopatologia e as apresentações clínicas > Amiloidose quote: Estudos demonstraram que a teoria autoimune pode ser o mecanismo fisiopatológico das formas “idiopáticas” de algumas síndromes disautonômicas, como a falência autonômica pura (FAP), SPOT ou a síndrome da fadiga crônica.43 note: 'Found by winnow, kev and lev in p124, p050. Claude judged: partial.' - paper: pmid31547756 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: There is an emerging body of evidence that suggests an autoimmune basis for POTS.3 Several studies have investigated the presence of autoantibodies in POTS and their effects on cholinergic and adrenergic receptors.3 note: 'Found by winnow, kev and lev in p003, p004, p005. Claude judged: partial.' - paper: pmid29682372 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The Mayo Clinic experience study showed some correlation between autoimmunity and POTS. This study entails specific antibodies, such as ganglionic acetylcholine receptor antibody [8] and alpha-1 adrenergic receptor antibody that act as partial antagonists and induce reflex compensatory sympathetic activation [9]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Autoimmune/Autoantibodies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p031, p032. Claude judged: partial.' - paper: pmid19058765 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - pots papers: 48 evidence: - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Around 30–60% of POTS patients have symptoms consistent with the ‘hyperadrenergic POTS’ subtype, characterized by palpitations, tremulousness, and gastrointestinal (GI) symptoms.[9] Patients with this subtype have elevated standing plasma norepinephrine concentrations causing increased sympathetic activation.[3] note: 'Found by winnow, kev and lev in p010, p016, p024. Claude judged: supports.' - paper: pmid38168762 cited: true text: full license: by verdict: supports section: Results > Phenotypes quote: Hyperadrenergic POTS was the most common phenotype (75.0%, 264/352), followed by hypovolemic POTS (44.9%, 158/352) and neuropathic POTS (37.8%, 133/352). note: 'Found by winnow, kev and lev in p005, p011, p023. Claude judged: supports.' - paper: pmid37508741 cited: true text: full license: by verdict: supports section: 1. Introduction quote: It is currently known to be associated with autonomic nerve dysfunction, hypovolemia, hyperadrenergic stimulation, deconditioning, hypervigilance and damaged skeletal muscle pump activity, etc., and these mechanisms may exist alone or in combination in patients with POTS [2,3]. note: 'Found by winnow, kev and lev in p019, p002. Claude judged: supports.' - paper: pmid37508589 cited: true text: full license: by verdict: supports section: 3. Main Pathogenesis of POTS quote: A plasma proteomic study revealed that the adrenergic activity was increased in the patients with POTS compared with healthy controls [35]. High plasma norepinephrine (NE) levels were found in some children or adults with POTS and were positively correlated with symptom severity [23,36]. note: 'Found by winnow, kev and lev in p011, p031, p032. Claude judged: supports.' - paper: pmid35232225 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35232225. Found by winnow, kev and lev in p003, p007, p022. Claude judged: supports.' - paper: pmid32621993 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32621993. Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Feigofsky examines quote: While the definite pathophysiology remains unknown, POTS is sometimes associated with chronic fatigue syndrome,2 several autoimmune disorders,3 Ehlers–Danlos syndrome type 3,4–6 mast cell activation syndrome,6,7 and hyperadrenergic states.7 note: 'Found by winnow, kev and lev in p019, p011. Claude judged: supports.' - paper: pmid31788462 cited: true text: full license: by verdict: supports section: Discussion quote: Other than that, the clearance mechanism of norepinephrine in POTS patients is damaged and their sympathetic activation is prominent (27, 28). note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.2 Hyperadrenergic State quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p022, p016, p017. Claude judged: supports.' - paper: pmid25120493 cited: true text: full license: by verdict: supports section: Sympathetic overactivity may be associated with POTS quote: Some investigations (Streeten et al., 1988; Schondorf and Low, 1993; Furlan et al., 1998; Jacob et al., 1999), but not all (Jacob et al., 2000; Lambert et al., 2008), have reported that POTS patients have greater systemic plasma noradrenaline concentrations at rest or during orthostasis compared with healthy controls, suggesting that POTS is associated with a hyperadrenergic state. note: 'Found by winnow, kev and lev in p017, p019. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p003, p001, p024. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p018, p009, p015. Claude judged: supports.' - paper: pmid23538032 cited: true text: full license: none verdict: supports section: DISCUSSION > Possible Mechanisms of Poor Sleep Quality quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23538032. Found by winnow, kev and lev in p005, p033, p038. Claude judged: supports.' - paper: pmid21266211 cited: true text: full license: none verdict: supports section: Discussion > Pathophysiological Role of Ang II in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21266211. Found by winnow, kev and lev in p030, p004, p021. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: As a part of the definition, POTS is associated with a hyperadrenergic state (Table 1). note: 'Found by winnow, kev and lev in p028, p033, p001. Claude judged: supports.' - paper: pmid42254140 cited: true text: full license: by verdict: partial section: Body quote: Evidence suggests that during sleep, POTS patients can enter a hyperadrenergic state, disrupting normal autonomic regulation and perpetuating a vicious cycle of poor sleep and worsened daytime symptoms[4]. note: 'Found by winnow, kev and lev in p003, p002. Claude judged: partial.' - paper: pmid41924132 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Additionally, heightened vascular distensibility promotes venous pooling in the extremities and may precipitate a maladaptive autonomic adrenergic response with associated dizziness and palpitations, as seen in POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid41533304 cited: true text: full license: by verdict: partial section: Discussion quote: We previously reported a subset of patients with POTS characterized by augmented central sympathetic outflow, as assessed by increased resting sympathetic nerve traffic (MSNA), and associated with greater diastolic blood pressure response to phase 2 of the VM (DBPVM2l_rise) [8]. This central hyperadrenergic phenotype was accompanied by increased resting blood pressure and an increase in upright BP. note: 'Found by winnow, kev and lev in p035, p036, p001. Claude judged: partial.' - paper: pmid41300853 cited: true text: full license: by verdict: partial section: 4. Discussion > 4.2. ME/CFS Patients with MCA Involvement Experience OI Significantly More Often, Particularly Its Subtype POTS quote: IF-channel inhibitors, commonly used in angina pectoris and heart failure, are increasingly prescribed off-label for POTS, particularly the hyperadrenergic POTS subtype, where patients experience excessive tachycardia upon standing [34,35]. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: partial section: Conclusions quote: In patients with POTS, orthostatic increases in NE levels significantly correlated with HR changes and elevated activity of naturally occurring AR autoantibodies, supporting exaggerated sympathetic activation as a key mechanism. note: 'Found by winnow, kev and lev in p025, p044, p004. Claude judged: partial.' - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: The increase of catecholamine is one of the main pathogenesis of POTS (Liao et al., 2013). note: 'Found by winnow, kev and lev in p020, p007. Claude judged: partial.' - paper: pmid39768649 cited: true text: full license: by verdict: partial section: Abstract quote: In POTS patients with a HR increase ≥40 bpm, this inverse relation was lost, and SVI changes were significantly less compared to POTS patients with a HR increase between 30–39 bpm, suggestive of a hyperadrenergic response. note: 'Found by winnow, kev and lev in p001, p004, p026. Claude judged: partial.' - paper: pmid39301475 cited: true text: full license: by verdict: partial section: Relationship to post-infectious syndromes including long COVID quote: In patients with LC and dysautonomia, there is often a hyperadrenergic state, which drives many of the pathophysiologic mechanisms of hyperadrenergic POTS (25). note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid39109428 cited: true text: full license: none verdict: partial section: 'Abstract > Background:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p024, p034, p001. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome quote: POTS is theorized to be the culmination of multiple underlying pathological processes, including peripheral neuropathy/denervation, hypovolemia with altered renin–aldosterone levels, and a hyperadrenergic state. note: 'Found by winnow, kev and lev in p011, p009, p013. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: Although the exact pathophysiology mechanism is unclear, it is thought that the combination of autoimmunity, relative central hypovolemia, small fiber neuropathy, hyperadrenergic stimulation, and pro-inflammatory cytokine production (i.e., cytokine storm) is a critical factor in POTS and COVID-19 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37705599 cited: true text: full license: by verdict: partial section: Discussion > VVS combined with POTS group quote: Some children with POTS display amplified sympathetic tone, while others demonstrate reduced sympathetic activity. The latter form of POTS, known as hyperadrenergic POTS, constitutes approximately 10% of all POTS cases (27). note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 3. Etiopathogenic basis quote: The pathophysiological mechanisms resulting in autonomic dysfunction in POTS may include sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac sympathoexcitation response (hyperadrenergic POTS) with increased serum norepinephrine, volume dysregulation (hypovolemia), baroreceptor dysfunction, peripheral neuropathy, and autoimmunity due to molecular mimicry following infections by pathogens such as Epstein–Barr virus, cytomegalovirus, or Borrelia Burgdorferi (1, 15). note: 'Found by winnow, kev and lev in p006, p015. Claude judged: partial.' - paper: pmid37378164 cited: true text: full license: by verdict: partial section: Introduction quote: It can also be divided into hyperadrenergic POTS, an excessive outburst of norepinephrine when initiating an erect position. note: 'Found by winnow, kev and lev in p003, p006, p008. Claude judged: partial.' - paper: pmid37255928 cited: true text: full license: by verdict: partial section: Associations with mast cell activation disorders quote: These MCA/POTS patients had predominant flushing breathlessness, headache, lightheadedness, excessive diuresis, diarrhoea, nausea and vomiting, and had a marked hyperadrenergic orthostatic response, with higher noradrenaline levels and exaggerated blood pressure rise on standing compared with the POTS and control groups [95]. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: As compared to healthy people, POTS patients have evidence of higher levels of catecholamines [28] and angiotensin II [29] and lower levels of plasma renin and aldosterone [14,17,23] at baseline. There is also evidence that with standing POTS, patients have an increase in norepinephrine levels. note: 'Found by winnow, kev and lev in p003, p013, p014. Claude judged: partial.' - paper: pmid35818599 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: The clinical presentation of pheochromocytoma may often be confused with POTS because of the paroxysms of hyperadrenergic symptoms.1 note: 'Found by winnow, kev and lev in p001, p011. Claude judged: partial.' - paper: pmid35620060 cited: true text: full license: by-nc verdict: partial section: Patient 3 quote: 'Given her symptoms of flushing, anxiety, and faintness upon assuming an upright position, supine (685 pg/mL) and standing (1386 pg/mL) norepinephrine levels were assessed and suggested hyperadrenergic POTS.' note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid35351159 cited: true text: full license: by verdict: partial section: Discussion > Comorbidities of patients with PF quote: Often, subjects with β-adrenergic hyperresponsiveness show symptoms of POTS [15, 16]. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Symptoms > BMI decrease in POTS quote: Increased angiotensin II within the CNS can produce sympatho-excitation, which is a major factor in the subgroup of hyperadrenergic POTS. note: 'Found by winnow, kev and lev in p014, p018. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p026, p014, p025. Claude judged: partial.' - paper: pmid33654569 cited: true text: full license: by verdict: partial section: Discussion quote: A significant subset of POTS patients experience persistent sympathetic activation due to hemodynamic changes associated with POTS.14 note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid33371330 cited: true text: full license: by verdict: partial section: 4. Discussion > 4.3. Orthostatic Headaches and Migraine quote: On the other hand, Novak et al. reported that the pathogenesis of POTS appears to involve a hyperadrenergic state and distal neuropathy affecting sympathetic myocardial fibers [27]. note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid33178533 cited: true text: full license: by verdict: partial section: Discussion quote: Hyperadrenergic POTS is associated with very high erect norepinephrine levels due to sympathetic overactivity or a hyperadrenergic state [12]. note: 'Found by winnow, kev and lev in p023, p001, p006. Claude judged: partial.' - paper: pmid32974246 cited: true text: full license: by verdict: partial section: Perspectives on the Pathogenesis of Pots > Abnormal Autonomic Reflexes and a “Hyperadrenergic” Status quote: However, some pediatric POTS patients with a “hyperadrenergic” background have an inability to buffer the decrease in baroreceptor activation, leading to persistent sympathetic excitation characterized by sustained tachycardia while in an upright position (3, 37). note: 'Found by winnow, kev and lev in p012, p011, p013. Claude judged: partial.' - paper: pmid30076469 cited: true text: full license: by verdict: partial section: Treatment by comorbidity, subgrouping, and genetic profile > Treatment by comorbidity quote: POTS (14% in our cohort, 38% of tested adolescents) commonly affects adolescents with CVS [7, 18, 31]. There is evidence of altered autonomic tone at baseline with elevated sympathetic tone and low to normal parasympathetic tone [29]. note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - paper: pmid29682372 cited: true text: full license: by verdict: partial section: 3. Discussion quote: Several mechanisms have been proposed for the development of these symptoms including sympathetic denervation and central causes such as sympathetic overdrive, hypovolemia, and involvement of the renin-angiotensin-aldosterone system. note: 'Found by winnow, kev and lev in p010, p011. Claude judged: partial.' - paper: pmid27558116 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27558116. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Central Hyperadrenergic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p029, p016, p026. Claude judged: partial.' - paper: pmid21906029 cited: true text: full license: by-nc verdict: partial section: Abstract quote: CFS–POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. note: 'Found by winnow, kev and lev in p001, p026, p033. Claude judged: partial.' - paper: pmid21802629 cited: true text: full license: none verdict: partial section: 4. Discussion > 4.2 Review of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21802629. Found by winnow, kev and lev in p035, p009. Claude judged: partial.' - paper: pmid15710782 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15710782. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid11206727 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 11206727. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - mast_cell_activation - associated_with - pots papers: 44 evidence: - paper: pmid41924132 cited: true text: full license: by-nc verdict: supports section: Abstract > Objective quote: The reported associations between EDS/HSD, Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS) further complicate the diagnosis and management of the VCS in this specific patient population. note: 'Found by winnow, kev and lev in p024, p001, p003. Claude judged: supports.' - paper: pmid41753313 cited: true text: full license: by verdict: supports section: 4. Discussion quote: These data show that inflammatory symptoms that are likely consistent with MCAS occur much more frequently with postural orthostatic tachycardia in adolescents and young adults than was previously recognized, and that joint hypermobility remains very common in this population, as well. note: 'Found by winnow, kev and lev in p001, p010, p018. Claude judged: supports.' - paper: pmid41668453 cited: true text: full license: by verdict: supports section: Introduction quote: A growing body of literature suggests that a subset of patients with POTS also have mast cell activation syndrome (MCAS), a disorder of dysregulated mast cells with excessive mast cell mediator release, which can mimic or exacerbate dysautonomia through symptoms including tachycardia, flushing, GI sensitivities, headache, and cognitive dysfunction. note: 'Found by winnow, kev and lev in p006, p007, p008. Claude judged: supports.' - paper: pmid41300853 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Of interest, an association between neurological or cardiac symptoms, such as cognitive dysfunction or OI, particularly POTS (Postural Orthostatic Tachycardia Syndrome), is described not only in ME/CFS but also in Mast Cell Activation Syndrome (MCAS) patients [22,23,24]. note: 'Found by winnow, kev and lev in p001, p005, p018. Claude judged: supports.' - paper: pmid40856938 cited: true text: full license: by verdict: supports section: Discussion quote: Mast cell activation syndrome (MCAS) is also a common comorbid condition in POTS, which induces abdominal cramping and bloating associated with enhanced secretion of histamine and inflammatory cytokines [1, 17]. note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Up to 30 percent of POTS patients have mast cell activation syndrome, and it is well known that EDS type III is a mast cell activation disorder [17,18,19]. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid40352770 cited: true text: full license: by verdict: supports section: Abstract > Background quote: The close association of syndromes of orthostatic intolerance with and without postural orthostatic tachycardia syndrome (POTS) with Joint Hypermobility Disorders (JHD) including Hypermobility Spectrum Disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS) and with Mast Cell Activation Syndrome (MCAS) is now firmly established. note: 'Found by winnow, kev and lev in p012, p027, p001. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Mast Cell Activation Syndrome quote: Mast cell activation syndrome (MCAS), a subset of mast cell activation disorder (MCAD), is one of the conditions that can be associated with POTS and is characterized by either early or excessive mast cell activation and histamine release.[13,14] note: 'Found by winnow, kev and lev in p017, p015, p016. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: 'Inflammation: In addition to elevated autoimmune and inflammatory markers in POTS patients [45] and a higher prevalence of autoimmune disorders [42], POTS frequently co-occurs with a range of other conditions that have inflammatory underpinnings, such as: Small Fiber Neuropathy (SFN), characterized by damage to small nerve fibers and inflammatory processes [46]; Mast Cell Activation Syndrome (MCAS), involving excessive inflammatory mediator release [47]; Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME), associated with immune dysregulation and chronic inflammation [48]; and infections such as Lyme disease [49].' note: 'Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Results > Response to Guanfacine in POTS Patients with and without Hyperadrenergic Phenotype (Protocol 2, Treatment Cohort). quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p024, p034, p035. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Potential mechanisms of infection-associated dysautonomia > Chronic neuroinflammation quote: POTS has been associated with mast cell activation syndrome (MCAS) (77), a poorly understood multisystem disorder of inflammation, with or without allergic phenomena or tissue growth/development anomalies (78). note: 'Found by winnow, kev and lev in p021. Claude judged: supports.' - paper: pmid38003876 cited: true text: full license: by verdict: supports section: Abstract quote: All eight patients were subsequently diagnosed with mast cell activation syndrome; six had comorbid autonomic disorders, the most common being postural orthostatic tachycardia syndrome; and four had hypermobile Ehlers-Danlos syndrome. note: 'Found by winnow, kev and lev in p001, p005, p016. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Associations with mast cell activation disorders quote: A prominent overlapping symptom cluster associated with both POTS [56, 57] and Long Covid [89, 90] includes a multi-system and often non-specific symptom cluster which is often referred to as ‘mast cell activation syndrome’ (and considered to be due to release of mast cell mediators) and includes gastrointestinal disturbances (nausea, vomiting, diarrhoea, cramps), asthma like symptoms, flushing, urticaria, angioedema and constitutional symptoms such as fatigue and fever [91]. note: 'Found by winnow, kev and lev in p026, p028. Claude judged: supports.' - paper: pmid37241210 cited: true text: full license: by verdict: supports section: 3. Association with Postural Tachycardia Syndrome, Reduced Cerebral Blood Flow and Orthostatic Intolerance quote: The association of MCA with POTS, as an example for orthostatic stress, may be via ME/CFS or separate. note: 'Found by winnow, kev and lev in p023, p001, p027. Claude judged: supports.' - paper: pmid37234076 cited: true text: full license: by verdict: supports section: 'Female reproductive health in illnesses comorbid or associated with Long COVID: A brief overview of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS), and endometriosis > Ehlers-Danlos syndrome (EDS), connective tissue disorders (CTDs), and reproductive health' quote: Notably, symptoms of MCA are prevalent in LC patients (62), and there are substantial rates of diagnostic comorbidity between mast cell activation syndrome (MCAS) and EDS (63), ME/CFS (64), and POTS (65). note: 'Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid36981522 cited: true text: full license: by verdict: supports section: '3. Treatment > 3.2. Comment: Allergic and Mast Cell Inflammation' quote: Some forms of POTS have been associated with mast cell activation syndrome [32] (MCAS), and POTS has been identified as part of the phenotype of hereditary forms of tryptasemia [33]. note: 'Found by winnow, kev and lev in p023, p001, p018. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Results > Mast Cell Activation Syndrome quote: MCAS is a common co-morbidity with both POTS and EDS and is a multi-systemic disorder of mast cell hyperactivity that typically manifests with allergic symptoms, gastrointestinal dysfunction, dysautonomia and various genito-urinary and gynecologic manifestations.26–28 note: 'Found by winnow, kev and lev in p027, p017. Claude judged: supports.' - paper: pmid36252987 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: The importance of diagnosing BASCULE syndrome lies in its association with a spectrum of orthostatic intolerance conditions, including syncope, orthostatic hypotension and POTS (a condition associated with mast cell activation and hypermobility spectrum disorders).2,3 note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid35307584 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35307584. Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid35062788 cited: true text: full license: by verdict: supports section: Abstract quote: There is rising recognition, too, of associations of MCAS with central and peripheral neuropathic disorders, including autonomic disorders such as POTS. note: 'Found by winnow, kev and lev in p001, p007, p020. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mechanisms quote: Mast cell activation syndrome may be present in some patients with POTS.14 These patients experience severe episodic flushing with sinus tachycardia.14 note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Furthermore, mast cell activation disorder (MCAD), a condition in which mast cells increase in number or excessively release inflammatory mediators,31 was considered to be a comorbidity of adult POTS, and some of which might be secondary to allergic disorders.32,33 note: 'Found by winnow, kev and lev in p024, p029. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: supports section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Nos casos de pacientes com SPOT que apresentam a síndrome de ativação dos mastócitos, um fator autoimune pode estar presente. Esses pacientes apresentam rubor da pele e hipertensão associada com a taquicardia ortostática. note: 'Found by winnow, kev and lev in p107, p124. Claude judged: supports.' - paper: pmid33178533 cited: true text: full license: by verdict: supports section: Discussion quote: Weinstock et al. report the successful treatment of POTS associated with mast cell activation syndrome with intravenous immunoglobulin [18]. note: 'Found by winnow, kev and lev in p023, p025. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Feigofsky examines quote: While the definite pathophysiology remains unknown, POTS is sometimes associated with chronic fatigue syndrome,2 several autoimmune disorders,3 Ehlers–Danlos syndrome type 3,4–6 mast cell activation syndrome,6,7 and hyperadrenergic states.7 note: 'Found by winnow, kev and lev in p006, p019. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome can occur in association with mast cell activation disorders, in which mast cells degranulate inappropriately and release mediators or proliferate to produce inflammatory responses that can occur throughout the body, as mast cells are present in all types of tissues.75 note: 'Found by winnow, kev and lev in p032. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.5 Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Background quote: To further complicate matters, 17 of 48 MCAS symptoms overlap with 33 POTS symptoms which is explained by comorbidity of the syndromes, where 30% of patients with POTS also have MCAS.5 note: 'Found by winnow, kev and lev in p002, p014, p015. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p018, p028. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: Some patients with POTS have co-existent mast cell activation. These patients have episodic flushing and abnormal increases in urine methylhistamine (the primary urinary metabolite of histamine) [20]. note: 'Found by winnow, kev and lev in p033, p019. Claude judged: supports.' - paper: pmid15710782 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15710782. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid42153984 cited: true text: full license: by verdict: partial section: Discussion > Comorbidities quote: The proportion of patients with gastroparesis and mast cell activation syndrome (MCAS) were similar to a large survey [18]. note: 'Found by winnow, kev and lev in p047, p049. Claude judged: partial.' - paper: pmid41898333 cited: true text: full license: by verdict: partial section: 12. Discussion quote: Moreover, other heterogeneous conditions, like HSD, mast cell activation disorder, and POTS, may cause similar symptoms together and separately, complicating our overall understanding of the disease process. note: 'Found by winnow, kev and lev in p017, p037. Claude judged: partial.' - paper: pmid39931100 cited: true text: full license: by verdict: partial section: Introduction quote: Notably, individuals with symptoms of hEDS often present with concomitant autonomic and immune dysfunctions such as postural orthostatic tachycardia syndrome (POTS) and mast cell activation disorder (MCAD), respectively, whose associations with connective tissue and joint fragility are well documented (10, 19). note: 'Found by winnow, kev and lev in p003, p006. Claude judged: partial.' - paper: pmid39165715 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: Of these 69 patients, 44 expressed additional symptoms suggesting MCA. Among them, 29 (66%) patients exhibited at least one laboratory abnormality related to MCA. note: 'Found by winnow, kev and lev in p024, p026, p001. Claude judged: partial.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. note: 'Found by winnow, kev and lev in p006, p001, p024. Claude judged: partial.' - paper: pmid38348221 cited: true text: full license: by verdict: partial section: 1 Introduction quote: Mast cell activation disorder has been proposed to be associated with POTS with atypical symptom presentation, such as predominant gastrointestinal (GI) symptomatology (Kohno et al., 2021). note: 'Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid38269002 cited: true text: full license: by verdict: partial section: Discussion quote: Hypersensitivity, likely related to MCAS development, has been shown to be associated with EDS and POTS, and atopic conditions like eosinophilic esophagitis have been found to manifest in these patients (21). note: 'Found by winnow, kev and lev in p016, p019. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Selected Etiology: Mast Cell Disorders > Main Points: > DIAGNOSIS:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p080. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: Flushing, headaches, and gastrointestinal symptoms are more prevalent in these individuals, and a recent study showed markedly elevated prostaglandins and histamine markers in patients with gastrointestinal complaints, reinforcing the case for a mast cell activation disorder in a subset of POTS patients [78]. A case of mast cell activation syndrome was described in a 50-year-old female with previous COVID-19 with signs and symptoms of POTS [52]. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid34398691 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Methods and Results quote: Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. note: 'Found by winnow, kev and lev in p001, p006, p002. Claude judged: partial.' - paper: pmid33869099 cited: true text: abstract license: none verdict: partial section: Abstract > Unlabelled quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33869099. Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - paper: pmid30400667 cited: true text: full license: by verdict: partial section: 2. Materials and Methods > 2.4. Laboratory Testing quote: Testing for Mast Cell Activation Disorder (MCAD) and food allergies included serum histamine, tryptase, chromogranin A, and IgE blood tests, respectively, (occasionally IgG4 delayed food allergy hypersensitivity testing was performed), when clinically indicated (MCAD can also be associated with POTS) [86]. note: 'Found by winnow, kev and lev in p038. Claude judged: partial.' - edge: - gi_dysmotility - associated_with - pots papers: 35 evidence: - paper: pmid42691689 cited: true text: full license: none verdict: supports section: Autonomic system degenerations, generalized dysautonomia, and disorders of autonomic dysregulation > Postural orthostatic tachycardia syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42691689. Found by winnow, kev and lev in p002, p044. Claude judged: supports.' - paper: pmid42509985 cited: true text: full license: by verdict: supports section: Abstract > Abstract quote: Dysautonomia, including postural orthostatic tachycardia syndrome (POTS) and related orthostatic disorders, is frequently associated with debilitating gastrointestinal (GI) symptoms in adolescents, including chronic nausea, early satiety, postprandial fullness, and functional dysmotility. note: 'Found by winnow, kev and lev in p003, p027, p004. Claude judged: supports.' - paper: pmid42156945 cited: true text: full license: by verdict: supports section: Introduction quote: IBS is a common comorbid disease in POTS14. note: 'Found by winnow, kev and lev in p004, p033, p037. Claude judged: supports.' - paper: pmid42153984 cited: true text: full license: by verdict: supports section: Discussion > Comorbidities quote: Most participants reported one or more of the common POTS comorbidities. More patients had irritable bowel syndrome, autoimmune disease, myalgic encephalomyelitis/chronic fatigue syndrome, and neuropathy than other findings [18, 21]. note: 'Found by winnow, kev and lev in p004, p047. Claude judged: supports.' - paper: pmid41952405 cited: true text: full license: by-nc verdict: supports section: Introduction quote: GI dysmotility, driven by autonomic dysfunction and hypovolemia, is a major contributor to these symptoms.8 GI symptoms, including nausea, vomiting, and indigestion, which commonly develop and persist even without postural changes,8 affect approximately 67% of POTS patients, severely impacting their quality of life (QoL).7,9 note: 'Found by winnow, kev and lev in p016, p006, p027. Claude judged: supports.' - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Discussion quote: Abnormal gastric emptying and delayed colonic transit were observed in over one‐third of POTS patients studied. note: 'Found by winnow, kev and lev in p032, p039, p041. Claude judged: supports.' - paper: pmid41858767 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Gastrointestinal symptoms in POTS and HSD/hEDS occur frequently, both as functional gastrointestinal disorders and as more severe intestinal dysmotility disorders (10-12). note: 'Found by winnow, kev and lev in p004, p001, p015. Claude judged: supports.' - paper: pmid40856938 cited: true text: full license: by verdict: supports section: Discussion quote: Abdominal pain frequently causes significant morbidity in patients with POTS. The underlying pathophysiology is multifactorial and could involve both autonomic and non-autonomic mechanisms. Frequently, patients present symptoms such as early satiety, constipation, bloating, and gastrointestinal dysmotility, including delayed gastric emptying and intestinal dysmotility. note: 'Found by winnow, kev and lev in p014, p015, p018. Claude judged: supports.' - paper: pmid40608783 cited: true text: full license: by verdict: supports section: 1. Introduction quote: We have previously shown that gastrointestinal symptoms were common and moderately severe in POTS, resembling the symptomatology found in irritable bowel syndrome (IBS), as well as in gastroparesis [15]. note: 'Found by winnow, kev and lev in p005, p014, p021. Claude judged: supports.' - paper: pmid39268060 cited: true text: full license: by verdict: supports section: Overview of gastroparesis > Normal gastric function quote: Gastric dysmotility is associated with conditions such as EDS and POTS which occur from disruptions to normal gastric function. note: 'Found by winnow, kev and lev in p001, p005, p042. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: Abstract quote: Gastrointestinal (GI) symptoms are common in postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p003, p035, p001. Claude judged: supports.' - paper: pmid35307584 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35307584. Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid34765384 cited: true text: full license: by verdict: supports section: Discussion quote: One retrospective study found that both EDS III and POTS are independent risk factors for gastrointestinal (GI) symptoms, including GI dysmotility and gastroesophageal reflux disease [15]. note: 'Found by winnow, kev and lev in p006, p019. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Gastrointestinal dysfunction in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid33621398 cited: true text: full license: by verdict: supports section: Discussion quote: Sullivan et al. assessed a group of children with functional GI symptoms, mainly abdominal pain, nausea, and vomiting, who also underwent tilt table testing, and demonstrated an association with either POTS, neutrally mediated hypotension, or POTS with neutrally mediated hypotension. note: 'Found by winnow, kev and lev in p024, p027. Claude judged: supports.' - paper: pmid33428036 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33428036. Found by winnow, kev and lev in p001, p004, p005. Claude judged: supports.' - paper: pmid32494413 cited: true text: full license: by verdict: supports section: Dr. Mehdirad remarks > Mechanisms and symptoms quote: It is noteworthy to mention additionally though that it is not uncommon for POTS patients to also demonstrate manifestations of other disease states such as hypermobility syndrome,8 vascular compression syndrome,9 and irritable bowel syndrome.8 In addition, some patients may present with cholinergic symptoms such as dry mouth, dry eyes, delayed gastric transit, early satiety, nausea, constipation and Holmes–Adie pupil (ie, dilated pupil that constricts slowly in bright light).10–13 note: 'Found by winnow, kev and lev in p005, p006. Claude judged: supports.' - paper: pmid32489735 cited: true text: full license: by verdict: supports section: Abstract quote: 'On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility.' note: 'Found by winnow, kev and lev in p052, p054, p006. Claude judged: supports.' - paper: pmid30072778 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30072778. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Introduction > Concurrent clinical syndromes > Irritable bowel syndrome (IBS) quote: Symptoms of IBS, food intolerance and allergic sinusitis, are commonly reported in individuals with POTS.7 note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: supports section: Background quote: Gastrointestinal (GI) symptoms are common in both syndromes.1–4 6 GI symptoms in MCAS can be explained by inappropriate release of mediators from mast cells (MCs) with KIT mutations whereas GI motility disorders in POTS may be due to active autoimmune muscarinic antibodies causing autonomic imbalance in some patients (S Vernino, personal communication, 2017).2 note: 'Found by winnow, kev and lev in p002, p016, p019. Claude judged: supports.' - paper: pmid28191707 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28191707. Found by winnow, kev and lev in p001, p003, p004. Claude judged: supports.' - paper: pmid26671111 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26671111. Found by winnow, kev and lev in p004, p001. Claude judged: supports.' - paper: pmid25483980 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p004, p022, p024. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > GI Physiology and Pathophysiology as Related to POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p052, p095. Claude judged: supports.' - paper: pmid19424509 cited: true text: full license: by verdict: supports section: 1. Introduction quote: FGID's have been associated with orthostatic intolerance (OI), mainly postural tachycardia syndrome (POTS) and syncope [4, 6], but other associations have not been carefully evaluated. note: 'Found by winnow, kev and lev in p004, p003. Claude judged: supports.' - paper: pmid42437376 cited: true text: full license: by verdict: partial section: Abstract > Conclusions quote: Overall, > 60% of hEDS/HSD patients report chronic GI symptoms. DGBI, co‐morbidities, including POTS, were highly prevalent in hEDS/HSD patients. note: 'Found by winnow, kev and lev in p005, p042. Claude judged: partial.' - paper: pmid39543811 cited: true text: full license: by verdict: partial section: Abstract > Key Results quote: 'Patients segregated into three clusters: Cluster 0 (n = 466): hEDS/HSD+ functional foregut disorders (FFD) + irritable bowel syndrome (IBS); Cluster 1 (n = 180): hEDS/HSD+ IBS and Cluster 2 (n = 337): hEDS/HSD alone. In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2.' note: 'Found by winnow, kev and lev in p036, p047, p003. Claude judged: partial.' - paper: pmid34993884 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34993884. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid33150760 cited: true text: full license: by verdict: partial section: Results > POTS comorbidities quote: 'There were two patients with chronic gastritis. The following comorbidities were identified in one patient each: epilepsy, prior subarachnoid hemorrhage, anxiety, mitral valve insufficiency, obstructive sleep apnea, hypothyreosis, and irritable bowel syndrome.' note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - paper: pmid32803794 cited: true text: abstract license: none verdict: partial section: Abstract > Key Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32803794. Found by winnow, kev and lev in p003, p004. Claude judged: partial.' - paper: pmid29549458 cited: true text: full license: none verdict: partial section: Results > Postural Tachycardia Syndrome and Gastrointestinal Symptoms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p006, p011, p014. Claude judged: partial.' - paper: pmid24068608 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24068608. Found by winnow, kev and lev in p005, p003. Claude judged: partial.' - paper: pmid23708963 cited: true text: full license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23708963. Found by winnow, kev and lev in p019, p020, p004. Claude judged: partial.' - paper: pmid23212662 cited: true text: abstract license: none verdict: partial section: Abstract > Interpretation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23212662. Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - anxiety_depression - associated_with - pots papers: 32 evidence: - paper: pmid42787977 cited: true text: full license: by verdict: supports section: Introduction quote: Beyond these physical manifestations, patients with POTS frequently experience significant mental health challenges, including anxiety, depression, and reduced quality of life [4]. note: 'Found by winnow, kev and lev in p004, p005, p022. Claude judged: supports.' - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Discussion quote: Extra‐intestinal comorbidities, including anxiety, chronic fatigue, migraines, and depression, were reported in over one‐third of POTS patients, occurring more frequently than gastrointestinal conditions. note: 'Found by winnow, kev and lev in p032, p003, p004. Claude judged: supports.' - paper: pmid41740821 cited: true text: abstract license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41740821. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid40454385 cited: true text: full license: by verdict: supports section: Discussion quote: Studies indicated that 87% of patients with POTS experienced mild-to-moderate anxiety and depression, and over half reported disturbed sleep patterns (17, 18). Additionally, anxiety and depression levels could be positively correlated with POTS symptom severity (19–21). note: 'Found by winnow, kev and lev in p012, p001, p005. Claude judged: supports.' - paper: pmid40003288 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Finally, symptoms of anxiety and depression are often comorbid in pediatric patients with orthostatic intolerance and/or POTS [11,12,29] and frequently contribute to symptom burden and functional impairment, as well as having an impact on the HPA axis [30]. note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid39838139 cited: true text: full license: by verdict: supports section: Introduction quote: Psychological similarities can also be identified between LC and POTS, such as higher levels of anxiety and depression [34–40] or lower levels of quality of life [10, 35, 41–46] compared with the general population. note: 'Found by winnow, kev and lev in p053, p008. Claude judged: supports.' - paper: pmid39308845 cited: true text: full license: by verdict: supports section: Introduction quote: Patients with POTS frequently experience a reduced quality of life, with many reporting co-occurring anxiety and depression, further complicating symptom management. note: 'Found by winnow, kev and lev in p003, p004, p009. Claude judged: supports.' - paper: pmid38240001 cited: true text: full license: by verdict: supports section: DISCUSSION quote: In this study, many patients with POTS had psychiatric symptoms caused by financial and educational concerns because of their inability to go to work or attend school and anxiety about prolonged symptoms. note: 'Found by winnow, kev and lev in p003, p023, p024. Claude judged: supports.' - paper: pmid37338634 cited: true text: full license: by verdict: supports section: Results quote: Common comorbidities include anxiety or depression, migraine, Ehlers–Danlos syndrome or hypermobile spectrum disorder, irritable bowel syndrome, iron deficiency, and myalgic encephalomyelitis or chronic fatigue syndrome (Table 1). note: 'Found by winnow, kev and lev in p014, p023. Claude judged: supports.' - paper: pmid33114659 cited: true text: full license: by verdict: supports section: 5. Study Limitations quote: Finally, it is well known that anxiety and psychological distress are common in POTS. note: 'Found by winnow, kev and lev in p057, p044. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Challenge II: Lack Of Standardized Approaches To Physical Rehabilitation And Psychopharmacology > Challenge III: Psychological Comorbidities' quote: Many teens with POTS report symptoms of depression, anxiety, and hyperactivity, with one study noting almost one-fourth of youth reported moderate to severe depressive symptoms (13% and 10%, respectively).5,11,23,47 note: 'Found by winnow, kev and lev in p006, p019, p020. Claude judged: supports.' - paper: pmid29628432 cited: true text: full license: none verdict: supports section: 2. Quality of Life and Psychiatric Profile of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29628432. Found by winnow, kev and lev in p001, p004, p009. Claude judged: supports.' - paper: pmid25852449 cited: true text: full license: by verdict: supports section: Introduction quote: PoTS has also been associated with symptoms of chronic fatigue and high levels of a number of other psychiatric symptoms particularly panic, anxiety and depression (Grubb et al., 2006; Garland et al., 2007; Thieben et al., 2007; Low et al., 2009; Freeman et al., 2011; Mathias et al., 2012). note: 'Found by winnow, kev and lev in p015, p001, p002. Claude judged: supports.' - paper: pmid25713509 cited: true text: full license: by verdict: supports section: Neurovisceral phenotypes > Postural Tachycardia Syndrome > Association with psychiatric disorders quote: Recent data suggests patients with POTS commonly present with symptoms of depression, elevated anxiety and increased anxiety sensitivity, particularly with regards to cardiac symptoms, and have a poorer health related quality of life in both the physical and mental health domains (Anderson et al., 2014). note: 'Found by winnow, kev and lev in p022, p001, p014. Claude judged: supports.' - paper: pmid25009504 cited: true text: full license: by verdict: supports section: Discussion quote: Patients with POTS commonly presented with symptoms of depression, elevated anxiety and increased anxiety sensitivity, and had a poorer subjective health related quality of life in both the physical and mental health domains. note: 'Found by winnow, kev and lev in p012, p018, p019. Claude judged: supports.' - paper: pmid23580201 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Individuals with POTS experience increased ratings of depression, anxiety and inattention/ADHD symptoms (Raj et al., 2009). note: 'Found by winnow, kev and lev in p018, p001, p003. Claude judged: supports.' - paper: pmid42342500 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42342500. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Study design quote: 'The POTS children were divided into two groups: anxiety/ depression group and non- anxiety / depression group according to the above scales scores.' note: 'Found by winnow, kev and lev in p001, p002, p007. Claude judged: partial.' - paper: pmid39884840 cited: true text: full license: by-nc verdict: partial section: Background quote: The prevalence of mental health symptoms in those with POTS is unknown, as some research has suggested that lifetime prevalence of depressive and anxiety disorders among POTS is similar to the general population (Raj et al., 2009) while other research has found increased rates of mild to moderate depression and anxiety (Attard et al., 2023). note: 'Found by winnow, kev and lev in p004, p041, p045. Claude judged: partial.' - paper: pmid39540412 cited: true text: full license: by-nc verdict: partial section: What Not to Do in Clinic quote: Even so, labels of anxiety and other psychiatric diagnoses are likely to be applied to these patients along the way. In a survey of over 700 patients meeting criteria for POTS, 83% reported being given at least 1 psychiatric diagnosis prior to being diagnosed. note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - paper: pmid38003876 cited: true text: full license: by verdict: partial section: 7. Mast-Cell-Directed Treatment quote: In a case report, a MCAS patient with severe MCAS and postural orthostatic tachycardia syndrome experienced significant improvement with regard to depression, anxiety, and dysautonomia symptoms using intravenous immunoglobulin, LDN, and antibiotic treatment for small intestinal bacterial overgrowth [21]. note: 'Found by winnow, kev and lev in p001, p027. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Treatment > Nonpharmacologic interventions quote: Referral for psychological counseling may be of benefit to patients with POTS due to the sudden and unexpected changes in lifestyle that may result in depression or anxiety. Patients who have comorbid mental health disorders, including suicidal ideation, should be referred as appropriate based on the situation, such as to mental health providers, the ED, or crisis intervention services. note: 'Found by winnow, kev and lev in p032, p042. Claude judged: partial.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: partial section: Discussion quote: The second most common comorbidity in this study was psychological disorders. Psychological factors can not only amplify the objective discomfort resulting from OI but also add the diversification and complexity of the clinical manifestation in pediatric POTS. note: 'Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid34746821 cited: true text: full license: by-nc-nd verdict: partial section: Introduction > Origin(s) of dyspnea in POTS quote: However, their anxiety symptoms may be fundamentally distinct as studies attribute angst to somatic hypervigilance, meaning that they tend to report relatively mild, routine sensory information as more distressing or intense than normal (Benarroch, 2012) – perhaps a manifestation of augmented interoception. There is more consistent evidence of mild to moderate depression in POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid32993834 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32993834. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid32974246 cited: true text: full license: by verdict: partial section: Introduction quote: In pediatric POTS, poor health increases the rate of depression and anxiety in young patients and their parents, which has drawn increasing attention in recent years (9, 10). note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid32655482 cited: true text: full license: by verdict: partial section: Clinical Characteristic of Pots in Pediatric Patients quote: Psychiatric disorders including anxiety and depression are associated with POTS in child and adolescent family members of patients, and child patients with POTS often encounter tragic experiences after contracting the illness, with no regular attendance at school and social activities, underachievement, and frequent visits to doctors. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid28442939 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Another small study (n=15) found that the majority of POTS patients suffered from depression,2 while Raj et al found that the lifetime prevalence of major depressive disorder was not elevated.39 Clearly, the relationship between POTS and depression and their effect on disturbed sleep will require more study. note: 'Found by winnow, kev and lev in p004, p021, p024. Claude judged: partial.' - paper: pmid25001527 cited: true text: full license: none verdict: partial section: Discussion > Subjective Depression and Anxiety Symptoms and Cognitive Difficulties quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25001527. Found by winnow, kev and lev in p014, p021. Claude judged: partial.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: Fatigue > Psychological Correlates of Chronic Fatigue quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p016, p105, p107. Claude judged: partial.' - paper: pmid22156614 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22156614. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid18977825 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 18977825. Found by winnow, kev and lev in p031, p020, p021. Claude judged: partial.' - edge: - neuropathic_evidence - associated_with - pots papers: 30 evidence: - paper: pmid41301791 cited: true text: full license: by verdict: supports section: 4. Neurologic Evaluation > 4.2. Examination quote: At least 50% of patients with POTS have small fiber neuropathy, which warrants a careful neurologic sensory examination, including pinprick and temperature sensation, to help identify small fiber neuropathy [22]. note: 'Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Autoimmunity > Association with autonomic neuropathy quote: POTS and OCADs can often occur as part of, or in the context of, autonomic neuropathy. Experts who originally described POTS have considered it to be a limited or restricted form of autonomic neuropathy (Schondorf and Low, 1993; Vernino et al., 2008). note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid40271232 cited: true text: full license: by verdict: supports section: Introduction quote: Over half of POTS patients have impaired function of the peripheral sympathetic nervous system [7]. Neuropathic manifestations of POTS include decreased sweating and venous blood pooling in the legs due to insufficient peripheral vasoconstriction, which prevents the patient from maintaining blood pressure in the upper body upon standing [7,18]. note: 'Found by winnow, kev and lev in p008, p036, p001. Claude judged: supports.' - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 3. Discussion quote: 'POTS and SFN are comorbid conditions, with both being highly prevalent in patients with Long COVID: an estimated 30–75% of patients with Long COVID have POTS [6,7], and nearly 70% have autonomic dysfunction [8].' note: 'Found by winnow, kev and lev in p005, p013. Claude judged: supports.' - paper: pmid38537312 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38537312. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Neuropathy: It is estimated that up to half of the POTS cases have some form of small-fiber neuropathy, resulting in dysautonomia.' note: 'Found by winnow, kev and lev in p003, p013, p019. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Introduction quote: Various pathophysiologic mechanisms of POTS exist, but some common ones include hypovolemia, autoimmunity, and neuropathy. note: 'Found by winnow, kev and lev in p005, p001, p003. Claude judged: supports.' - paper: pmid36349067 cited: true text: full license: by verdict: supports section: Conclusions quote: There is an occurrence of small fiber neuropathy that occurs in POTS. note: 'Found by winnow, kev and lev in p037, p042, p004. Claude judged: supports.' - paper: pmid33490373 cited: true text: full license: by verdict: supports section: Discussion quote: Patient's with postural tachycardia syndrome have peripheral autonomic dysfunction. note: 'Found by winnow, kev and lev in p036, p029. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.1 Partial Sympathetic Neuropathy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p015, p016. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid23708963 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23708963. Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid19207771 cited: true text: full license: none verdict: supports section: Neuropathic POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19207771. Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid42153984 cited: true text: full license: by verdict: partial section: Discussion > Comorbidities quote: All but one participant in NOT IMPROVED had one or more of neuropathy, gastroparesis and overactive bladder symptoms, compared to only 20% of IMPROVED. An association between neuropathy and gastrointestinal and bladder symptoms bas been recognized in patients with POTS [25]. note: 'Found by winnow, kev and lev in p048. Claude judged: partial.' - paper: pmid41767063 cited: true text: full license: by verdict: partial section: Discussion quote: POTS is a heterogeneous and multifactorial disorder involving both peripheral and central autonomic pathways. In neuropathic POTS, peripheral autonomic injury—primarily small‐fiber neuropathy—is a core mechanism. note: 'Found by winnow, kev and lev in p023, p025. Claude judged: partial.' - paper: pmid40624434 cited: true text: full license: by verdict: partial section: Clinical features and evaluation of dysautonomia quote: A thorough cardiac and neurologic exams are recommended, including assessment of pinprick and temperature sensation to help identify small fiber neuropathy, a common comorbidity of POTS and other autonomic disorders [20]. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid40608783 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Moreover, post-ganglionic sudomotor dysfunction, measured by quantitative sudomotor axon reflex test (QSART), reflecting partial sympathetic denervation is common in various autonomic neuropathies [11] and is present in some POTS patients [9,12–14]. note: 'Found by winnow, kev and lev in p001, p004, p005. Claude judged: partial.' - paper: pmid39200375 cited: true text: full license: by verdict: partial section: 3. POTS Etiology and Its Complexity quote: 'Sympathetic denervation: Sympathetic denervation, characterized by a decrease in sympathetic nerve activity, is another factor contributing to autonomic dysfunction in POTS [38]. This denervation disrupts the intricate coordination between the nervous and cardiovascular systems, ultimately giving rise to the hallmark symptoms of POTS.' note: 'Found by winnow, kev and lev in p012, p013. Claude judged: partial.' - paper: pmid37968647 cited: true text: full license: by verdict: partial section: Introduction quote: The involvement of autonomic SFN can produce changes in sweating, dry mouth, and gastrointestinal and urinary problems, as well as POTS [17]. note: 'Found by winnow, kev and lev in p009, p004. Claude judged: partial.' - paper: pmid36639608 cited: true text: full license: none verdict: partial section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p025. Claude judged: partial.' - paper: pmid34055418 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The association between POTS and JHS can be explained by predominant peripheral neuropathy in the autonomous system and a failure of the peripheral vascular system to maintain resistance in areas exposed to stress due to orthostasis, blood stasis in the lower limbs, or pathologies of the central nervous system [11]. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid33764697 cited: true text: full license: by verdict: partial section: Introduction quote: Furthermore, in some patients with neuropathic POTS, intraepidermal nerve fiber density is decreased, providing objective support for a small fiber neuropathy in these POTS patients. note: 'Found by winnow, kev and lev in p003, p007, p029. Claude judged: partial.' - paper: pmid33459162 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33459162. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: PATHOPHYSIOLOGY OF POTS quote: The excessive sympathetic tone is considered to be of central origin in hyperadrenergic POTS, but smaller increases in plasma NE upon standing, which are not uncommon in POTS, may also result as a compensatory response to hypovolemia and peripheral autonomic neuropathy. note: 'Found by winnow, kev and lev in p031, p016. Claude judged: partial.' - paper: pmid29549458 cited: true text: full license: none verdict: partial section: Results > Postural Tachycardia Syndrome and Gastrointestinal Symptoms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p011, p024, p001. Claude judged: partial.' - paper: pmid27660311 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27660311. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid24819031 cited: true text: full license: none verdict: partial section: POTS > Potential “Etiologies” of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p044, p052, p068. Claude judged: partial.' - paper: pmid24647968 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24647968. Found by winnow, kev and lev in p004, p003. Claude judged: partial.' - paper: pmid24386408 cited: true text: full license: by verdict: partial section: Abstract > Results quote: Nine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). note: 'Found by winnow, kev and lev in p003, p020, p002. Claude judged: partial.' - paper: pmid16943900 cited: true text: full license: by verdict: partial section: Pathophysiology of POTS > Neuropathic POTS quote: Considering that POTS patients have high plasma NE levels, it would seem paradoxical that a neuropathy is proposed as an underlying process. Yet some of them have a form of dysautonomia, with preferential denervation of sympathetic nerves innvervating the lower limbs [22-24]. note: 'Found by winnow, kev and lev in p024, p027, p042. Claude judged: partial.' - edge: - me_cfs - associated_with - pots papers: 29 evidence: - paper: pmid42746015 cited: true text: full license: by verdict: supports section: Abstract > Introduction quote: Postural orthostatic tachycardia syndrome (PoTS) can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). note: 'Found by winnow, kev and lev in p005, p001, p003. Claude judged: supports.' - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Introduction quote: Patients with POTS often have a higher prevalence of various comorbidities, including chronic fatigue syndrome, syncope, migraines, fibromyalgia, joint hypermobility, Ehlers‐Danlos Syndrome, hypervigilance, anxiety, concussions, and autoimmune disorders [3]. note: 'Found by winnow, kev and lev in p007, p004, p005. Claude judged: supports.' - paper: pmid41932997 cited: true text: full license: by verdict: supports section: Results > Proteomic alterations associated with POTS status in ME/CFS quote: These findings suggest that the comorbid POTS phenotype in ME/CFS may be associated with innate immune activation and platelet-mediated inflammation. note: 'Found by winnow, kev and lev in p019, p009. Claude judged: supports.' - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 as part of Long COVID and is a common comorbidity of ME/CFS.8,9 note: 'Found by winnow, kev and lev in p005, p007. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: POTS is well known to be associated with several conditions, such as chronic fatigue syndrome and joint hypermobility, specifically Ehlers-Danlos syndrome type III, which have been linked to extra-articular manifestations such as dysautonomia and POTS [15]. note: 'Found by winnow, kev and lev in p080. Claude judged: supports.' - paper: pmid41300853 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Of interest, an association between neurological or cardiac symptoms, such as cognitive dysfunction or OI, particularly POTS (Postural Orthostatic Tachycardia Syndrome), is described not only in ME/CFS but also in Mast Cell Activation Syndrome (MCAS) patients [22,23,24]. note: 'Found by winnow, kev and lev in p001, p005, p021. Claude judged: supports.' - paper: pmid41225175 cited: true text: full license: by verdict: supports section: Introduction quote: POTS and certain types of orthostatic intolerance often occur in patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [3] who usually require extensive medical care. According to several studies, the prevalence of POTS in ME/CFS is estimated between 11% [4] and 25%, but could be even higher because of a lack of diagnostic tests in clinical practice and sensitivity of some testing methods [5]. note: 'Found by winnow, kev and lev in p003, p084. Claude judged: supports.' - paper: pmid40761644 cited: true text: full license: by verdict: supports section: Introduction quote: Dysautonomic syndromes like classical and delayed orthostatic hypotension, neurally mediated hypotension, postural tachycardia syndrome (POTS), and orthostatic intolerance (OI) in the absence of heart rate and blood pressure changes are common in ME/CFS and can severely affect the patient’s daily life (5, 6). note: 'Found by winnow, kev and lev in p005, p019, p022. Claude judged: supports.' - paper: pmid40365455 cited: true text: full license: by verdict: supports section: Discussion > Study population and outcome measures quote: Finally, it is estimated that a fair proportion of patients with POTS also meet the current diagnostic criteria for ME/CFS (41–43), which is also characterized by multisystemic symptomatology including autonomic dysfunction, and is exemplified by moderate to severe PEM. note: 'Found by winnow, kev and lev in p041. Claude judged: supports.' - paper: pmid38650940 cited: true text: full license: by verdict: supports section: Conclusion quote: Our results also highlight a potential shared underlying mechanism between ME/CFS and its major comorbidities such as hEDS/HSD, POTS, MCAS, multiple chemical sensitivity, peripheral neuropathy, and the neuro-immune and brain-gut interaction axis. note: 'Found by winnow, kev and lev in p032, p082. Claude judged: supports.' - paper: pmid38540980 cited: true text: full license: by verdict: supports section: Abstract quote: During the tilt test, 32.5% of the participants demonstrated POTS or OH. The participants with either of these two common types of orthostatic intolerance were found to have more problems with sleep and post-exertional malaise as assessed by the DePaul Symptom Questionnaire; these patients also reported more physical and health function limitations. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: In particular, 11 to 50% of patients with ME/CFS may suffer from postural orthostatic tachycardia syndrome (POTS). note: 'Found by winnow, kev and lev in p054, p035, p046. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Results > Chronic Fatigue Syndrome quote: CFS is a common co-morbidity of POTS, with many patients qualifying for a diagnosis of CFS due to chronic fatigue and post-exertional malaise that are highly prevalent in patients with POTS. It has been estimated that at least 21% of POTS patients have concurrent CFS.1,2 note: 'Found by winnow, kev and lev in p028, p017. Claude judged: supports.' - paper: pmid35697326 cited: true text: full license: none verdict: supports section: Supportive Lifestyle Practices > Physical Activity quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35697326. Found by winnow, kev and lev in p022, p007. Claude judged: supports.' - paper: pmid35689118 cited: true text: full license: by verdict: supports section: Discussion quote: CFS, in particular, has been frequently observed in those with POTS [61, 62] and could exacerbate the cognitive impairments and fatigue associated with POTS (the association between POTS and fatigue is so prevalent that the designation “CFS-POTS” has been coined to reflect those who are diagnosed with POTS but also present with fatigue that meets the criteria for CFS). note: 'Found by winnow, kev and lev in p042, p028, p039. Claude judged: supports.' - paper: pmid35241011 cited: true text: full license: by verdict: supports section: Background quote: The association of dysautonomia, particularly in the form of POTS, with chronic fatigue syndrome and/or myalgic encephalomyelitis (CFS; ME) is also becoming more understood. note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: One of the possible explanations for the comorbidity with POTS may be immune mechanisms. OI is one of the common clinical manifestations of chronic fatigue syndrome. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid31159884 cited: true text: full license: by verdict: supports section: Discussion quote: Prior literature has established an association between OI symptoms and CFS, and comorbidity of POTS (OI symptoms plus postural tachycardia) and CFS [29–32]. note: 'Found by winnow, kev and lev in p026, p036, p040. Claude judged: supports.' - paper: pmid30505831 cited: true text: full license: by verdict: supports section: Introduction quote: Studies in the 1990s brought further attention to the association between ME/CFS and various forms of orthostatic hypotension or postural tachycardia syndrome (POTS) (3–8). note: 'Found by winnow, kev and lev in p005, p007, p016. Claude judged: supports.' - paper: pmid29876157 cited: true text: full license: by verdict: supports section: Review quote: According to Schondorf et al., 40% of patients with chronic fatigue syndrome also suffer from POTS; indeed, chronic fatigue syndrome (CFS) is frequent and of significant comorbidity in POTS [7]. note: 'Found by winnow, kev and lev in p007, p016. Claude judged: supports.' - paper: pmid29391028 cited: true text: full license: by verdict: supports section: Discussion quote: Our paper also draws attention to the potential for neurally mediated syncope and POTS to be associated with cervical myelopathy. Both hemodynamic abnormalities are strongly associated with ME/CFS [1, 33, 34], and treatment of the orthostatic intolerance can lead to improvements in ME/CFS symptoms and function [33]. note: 'Found by winnow, kev and lev in p015, p031. Claude judged: supports.' - paper: pmid28674681 cited: true text: full license: by verdict: supports section: Etiology and Pathophysiology > Pathophysiological Basis for Symptoms > Circulatory Abnormalities quote: Controlled studies have shown a higher prevalence of postural tachycardia syndrome (POTS) and neurally mediated hypotension (NMH) in pediatric patients with ME/CFS (49, 51–55). note: 'Found by winnow, kev and lev in p035, p189. Claude judged: supports.' - paper: pmid26425598 cited: true text: full license: by verdict: supports section: Introduction quote: Indeed, CFS is a frequent and major comorbidity in POTS.5,6 The 2 conditions frequently appear together, and research shows that there is a clinically identifiable subgroup of patients with CFS and orthostatic intolerance that differs from control subjects and from those with CFS without orthostatic intolerance.4 note: 'Found by winnow, kev and lev in p003, p007, p008. Claude judged: supports.' - paper: pmid24934205 cited: true text: full license: by-nc verdict: supports section: Results > Overall symptom burden of the groups quote: Around 20% of the total cohort reported having CFS and just under 20% had Ehlers-Danlos syndrome, but when we considered the PoTS UK population compared with the PoTS clinic cohort, this showed some interesting differences, with the PoTS clinic cohort having 42% of the cohort with comorbid CFS/myalgic encephalomyelitis (ME) compared with 26% of the PoTS UK having comorbid Ehlers-Danlos syndrome (EDS; table 1). note: 'Found by winnow, kev and lev in p033, p025, p027. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: supports section: Discussion quote: These data confirm the well-established overlap between the POTS and chronic fatigue syndrome [25-27]. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid21906029 cited: true text: full license: by-nc verdict: supports section: INTRODUCTION quote: A substantial overlap between POTS and CFS has been consistently reported in the literature [10,11,15,16]. The prevalence of POTS in CFS patients has ranged from 19% [7] to 70% [10], whereas studies in cohorts of patients selected for POTS have shown a prevalence of chronic fatigue between 48 and 77% [15,17], and CFS between 17 and 23% [17,18]. note: 'Found by winnow, kev and lev in p001, p002, p003. Claude judged: supports.' - paper: pmid41050528 cited: true text: full license: by-nc verdict: partial section: Case presentation quote: After a new COVID-19 infection in February 2021, he developed typical long COVID symptoms of dysautonomia, post-exertional malaise (PEM), and symptoms compatible with POTS. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid40978926 cited: true text: full license: by verdict: partial section: Case presentation quote: Passive standing tests conducted at home confirmed a >40 bpm increase in heart rate during the first 10 minutes of standing, compared to supine values. The test provoked typical orthostatic symptoms and no evidence of orthostatic hypotension, consistent with postural tachycardia syndrome (POTS) [14]. note: 'Found by winnow, kev and lev in p017. Claude judged: partial.' - paper: pmid33996867 cited: true text: full license: by verdict: partial section: Abstract quote: All patients reported orthostatic intolerance symptoms within the first 2 weeks of illness, and 10-min passive standing tests were consistent with postural tachycardia syndrome. After 6 months of illness, all three patients met criteria for ME/CFS. note: 'Found by winnow, kev and lev in p002, p006, p017. Claude judged: partial.' - edge: - sleep_disturbance - associated_with - pots papers: 24 evidence: - paper: pmid42254140 cited: true text: full license: by verdict: supports section: Body quote: Evidence suggests that during sleep, POTS patients can enter a hyperadrenergic state, disrupting normal autonomic regulation and perpetuating a vicious cycle of poor sleep and worsened daytime symptoms[4]. Recently, sleep disturbances among individuals with POTS have gained attention, however, limited discussion exists on the influence of modifiable lifestyle factors on this critical aspect of the condition. note: 'Found by winnow, kev and lev in p003, p005. Claude judged: supports.' - paper: pmid35742222 cited: true text: full license: by verdict: supports section: 3. Individualized Therapy > 3.1. Individualized Therapy for POTS > 3.1.1. Physiological Indicators Predicting the Efficacy of Non-Pharmacotherapy Treatment in Children with POTS quote: Patients with POTS have a significantly decreased quality of life because of sleep problems [56]. Children who sleep for less than 8 h a day have an almost six times higher risk of developing POTS than those with a daily sleep duration of ≥8 h [57]. note: 'Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid35689118 cited: true text: full license: by verdict: supports section: Results > Factors influencing fatigue in patients with orthostatic syncope quote: Four papers reported that patients with POTS [35, 42, 45] and VVS [46] have significant sleep problems, including poorer sleep quality and greater levels of sleep disturbances, relative to healthy controls [35, 42, 45, 46]. note: 'Found by winnow, kev and lev in p029, p024, p044. Claude judged: supports.' - paper: pmid35303039 cited: true text: full license: by verdict: supports section: Discussion quote: In addition, sleeping disorder was common in pediatric postural tachycardia syndrome (POTS) that was thought to have similar hemodynamic characteristics to pediatric STS [1, 21]. note: 'Found by winnow, kev and lev in p024, p006. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Sleeping disorders in children with POTS have attracted increasing attention. Like other behavioral problems in children, abnormal sleep is usually defined by parental observations. note: 'Found by winnow, kev and lev in p027. Claude judged: supports.' - paper: pmid33231164 cited: true text: abstract license: none verdict: supports section: Abstract > Study Objectives quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33231164. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid31024242 cited: true text: full license: by verdict: supports section: Discussion quote: In contrast, the PSQI score of >5 in our POTS cohort is indicative of poor sleep quality (Buysse et al., 1989) and also differed significantly from controls. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid29773483 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29773483. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29628432 cited: true text: full license: none verdict: supports section: 4. Potential Mechanisms Underlying Psychological and Cognitive Dysfunction in POTS > 4.4 Sleep Disturbances quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29628432. Found by winnow, kev and lev in p017, p029. Claude judged: supports.' - paper: pmid29163944 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Besides their chief complaint of orthostatic intolerance, sleep and fatigue probably rank as the most common and disabling complaints in children with POTS.3 note: 'Found by winnow, kev and lev in p004, p014, p006. Claude judged: supports.' - paper: pmid28442939 cited: true text: full license: by-nc verdict: supports section: Results > Sleep quote: According to the PSQI, 98.4% of POTS patients surveyed had poor sleep quality (compared to 69.4% of controls), and the POTS group had significantly worse mean overall sleep scores than controls (t[873]=17.75; p<0.001). note: 'Found by winnow, kev and lev in p003, p015, p016. Claude judged: supports.' - paper: pmid27206906 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 27206906. Found by winnow, kev and lev in p004, p001, p002. Claude judged: supports.' - paper: pmid26859225 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26859225. Found by winnow, kev and lev in p005, p014. Claude judged: supports.' - paper: pmid26695400 cited: true text: abstract license: none verdict: supports section: Abstract > Objective quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26695400. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid26611942 cited: true text: abstract license: none verdict: supports section: Abstract > Background And Aim quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26611942. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Disorders Overlapping with POTS > Chronic Fatigue Syndrome (CFS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid25071706 cited: true text: full license: by verdict: supports section: Abstract quote: Many patients with postural tachycardia syndrome (PoTS) suffer from fatigue, daytime sleepiness, and sleeping disturbances. note: 'Found by winnow, kev and lev in p017, p001, p003. Claude judged: supports.' - paper: pmid23999934 cited: true text: full license: none verdict: supports section: Conclusions > Sleep quality may affect brain fog quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23999934. Found by winnow, kev and lev in p020, p010. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Fatigue, Sleep Problems & Quality of Life in POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid23538032 cited: true text: full license: none verdict: supports section: RESULTS > Sleep Assessments by Sleep Logs (Table 2) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23538032. Found by winnow, kev and lev in p004, p008, p030. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: However, Bagai et al. found a higher prevalence of poor sleep quality in patients with POTS than in healthy control participants [2]. note: 'Found by winnow, kev and lev in p004, p022. Claude judged: supports.' - paper: pmid29876157 cited: true text: full license: by verdict: partial section: Review quote: Many chronically ill patients, including those with POTS, complain of poor sleep but a lack of sufficient data to link between POTS, depression, and disturbed sleep might have limited the variability, as explained by Pederson and Book [26]. note: 'Found by winnow, kev and lev in p014, p016. Claude judged: partial.' - paper: pmid28769598 cited: true text: full license: by-nc verdict: partial section: Body quote: However, sleep disturbance has not been thoroughly investigated as a cause of increased suicidal risk in patients with POTS. note: 'Found by winnow, kev and lev in p002, p006. Claude judged: partial.' - paper: pmid25474569 cited: true text: full license: by verdict: partial section: Introduction quote: Previous studies have suggested that compared with normal subjects, children with POTS sleep less. With fatigue, the symptoms of POTS get worse [15], [16]. note: 'Found by winnow, kev and lev in p028, p003, p006. Claude judged: partial.' - edge: - chronic_migraine - associated_with - pots papers: 20 evidence: - paper: pmid41420770 cited: true text: full license: none verdict: supports section: 'Abstract > Results:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41420770. Found by winnow, kev and lev in p003, p034, p006. Claude judged: supports.' - paper: pmid40585261 cited: true text: full license: by verdict: supports section: 'Abstract > Results:' quote: An abnormal cardiovascular response to tilt was present in the majority (63%) of which POTS was the most common etiology (56.2%). note: 'Found by winnow, kev and lev in p003, p036, p039. Claude judged: supports.' - paper: pmid40520610 cited: true text: full license: by verdict: supports section: Discussion quote: Compared to the general population, where 6.5% of men and 18.2% of women experience migraines, the PoTS population in previous studies demonstrates a greater prevalence of migraine of up to 40% (5, 20, 21). note: 'Found by winnow, kev and lev in p024, p026, p036. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Migraine Headaches quote: Migraines are frequently reported among POTS patients, although the etiology of this association is not understood.[44] note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid38966085 cited: true text: full license: by verdict: supports section: 'Discussion > Associated factor: migraine' quote: Migraine is one of the most common co-morbidities in POTS patients with studies reporting frequencies from 28 to 61% (23, 24). note: 'Found by winnow, kev and lev in p037, p038, p040. Claude judged: supports.' - paper: pmid38912309 cited: true text: full license: by verdict: supports section: Theoretical and auto/biographical review > Recovery and expectations quote: '‘A frequently described comorbidity in POTS patients is migraine, as well as other chronic headache types’ (Bryarly et al., 2019: 1216); ‘Intractable migraines often lead to physical inactivity, which may exacerbate orthostatic intolerance, and conversely, the increased sympathetic activity associated with POTS may contribute to increased frequency of headaches’ (Bryarly et al., 2019).' note: 'Found by winnow, kev and lev in p036. Claude judged: supports.' - paper: pmid36992793 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Postural Orthostatic Tachycardia Syndrome (POTS), a form of orthostatic intolerance, is common in patients with primary headache (Khurana and Eisenberg, 2011; Cook and Sandroni, 2018). note: 'Found by winnow, kev and lev in p004, p005. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Results > Migraine quote: It is estimated that 40% of POTS patients also experience migraine, making migraine a significant consideration when caring for pregnant women with POTS.1,2 note: 'Found by winnow, kev and lev in p015, p017, p018. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What other conditions commonly occur in patients with POTS? quote: Common comorbid conditions seen with POTS4,21 include hypermobile Ehlers–Danlos syndrome, mast cell activation syndrome,22 migraine and ME/CFS (Table 1).18 note: 'Found by winnow, kev and lev in p018, p006, p017. Claude judged: supports.' - paper: pmid34866935 cited: true text: full license: by-nc verdict: supports section: Discussion quote: Migraine and hyperventilation syndrome, which were also common comorbidities of pediatric POTS in our study, are thought to be related to autonomic nervous dysfunction. note: 'Found by winnow, kev and lev in p026, p022. Claude judged: supports.' - paper: pmid34246578 cited: true text: full license: by-nc-nd verdict: supports section: Pathophysiology of POTS quote: The associations of POTS with migraine headache, the hypermobile form of Ehlers-Danlos syndrome (hEDS) (De Wandele et al., 2014) and the hypermobility spectrum disorder, allergic disorders like mast cell activation syndrome (MCAS) (Shibao et al., 2005), and autoimmune disorders have been clearly described. note: 'Found by winnow, kev and lev in p023. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Clinical associations & co-morbidities quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p009, p014. Claude judged: supports.' - paper: pmid33174112 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33174112. Found by winnow, kev and lev in p001, p017, p019. Claude judged: supports.' - paper: pmid32823577 cited: true text: full license: by verdict: supports section: 1. Introduction quote: In addition, many patients experience other chronic conditions whose symptoms cannot be mechanistically explained by postural intolerance or excessive tachycardia [2]. These include the following:–visceral pain and dysmotility of the upper or lower gastrointestinal tract, bladder, and other organs [3,4];–chronic fatigue [5,6], fibromyalgia [7], and sleep disturbances [8];–joint hypermobility and Ehlers–Danlos syndrome type III [9,10]; –chronic headache, including migraine and orthostatic headache [11,12]. note: 'Found by winnow, kev and lev in p004, p036. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Part II: Recommendations For Treating Pain In Youth With POTS+Pain' quote: Chronic pain is a common occurrence among individuals with POTS, with headaches, migraines, abdominal pain, muscle cramping, joint pain, leg pain, and musculoskeletal pain being the most commonly reported types of pain.7,8,13,55–57 In fact, between 30% and 88% of youth with POTS report chronic daily headache, migraine, abdominal pain, and musculoskeletal pain.8,11–13 note: 'Found by winnow, kev and lev in p030, p004, p022. Claude judged: supports.' - paper: pmid31549738 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31549738. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Clinical Presentation of POTS > Common Clinical Features > Orthostatic symptoms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Headaches and POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p096, p052, p055. Claude judged: supports.' - paper: pmid20819844 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20819844. Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: partial section: Abstract quote: There are sporadic reports of the autonomic nervous system dysfunction in migraine and fibromyalgia. We report a case of POTS associated with migraine and fibromyalgia. note: 'Found by winnow, kev and lev in p001, p002, p012. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - associated_with - pots papers: 19 evidence: - paper: pmid41602336 cited: true text: full license: by verdict: supports section: Discussion quote: Patients with chronic fatigue, POTS, and fibromyalgia experience decreased blood flow to the brain (9, 11, 17, 18) and therefore vascularly linked. note: 'Found by winnow, kev and lev in p022, p025. Claude judged: supports.' - paper: pmid39544990 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: HYCH and POTS are syndromes of orthostatic intolerance with cerebral hypoperfusion associated with reduced orthostatic cerebral blood flow, hypocapnia, mild autonomic failure and small fiber neuropathy of a similar degree and distribution; except for tachycardia in POTS. note: 'Found by winnow, kev and lev in p036, p004, p025. Claude judged: supports.' - paper: pmid35891154 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Cerebral hypoperfusion secondary to hypocapnia is well documented in the literature to be associated with POTS diagnosis; however, it has not previously been evaluated in the other post-vaccine POTS cases. note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid32140630 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: First, our study shows that in response to head-up tilt, ME/CFS patients with either delayed orthostatic hypotension or POTS develop a cerebral blood flow reduction of 28%, and 29%, respectively, at the end of the upright position. This is highly significantly different from the 7% reduction in controls with a normal tilt test. note: 'Found by winnow, kev and lev in p073, p081, p082. Claude judged: supports.' - paper: pmid30256820 cited: true text: full license: by verdict: supports section: Introduction quote: Cerebral hypoperfusion in OI can be related to hypocapnia which causes cerebral vasoconstriction and reduces cerebral blood flow. This mechanism, e.g. hypocapnic cerebral hypoperfusion, was described in POTS [2]. note: 'Found by winnow, kev and lev in p024, p001, p004. Claude judged: supports.' - paper: pmid24711524 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24711524. Found by winnow, kev and lev in p034, p001, p004. Claude judged: supports.' - paper: pmid42605371 cited: true text: full license: by verdict: partial section: Abstract quote: The review found that abnormal cerebral blood flow (CBF) was reported in 61% of 56 POTS patients with cognitive dysfunction, and that sustained cognitive stress induced a greater reduction in CBF velocity in POTS patients than in controls, at approximately 7.8% and 1.8%, respectively. note: 'Found by winnow, kev and lev in p050, p001, p011. Claude judged: partial.' - paper: pmid41952073 cited: true text: full license: by verdict: partial section: Discussion quote: In an interesting study [39], out of 1925 patients presenting for autonomic function testing, patients reporting nausea were found to have decreased cerebral blood flow, which is associated with POTS. note: 'Found by winnow, kev and lev in p034. Claude judged: partial.' - paper: pmid41740821 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41740821. Found by winnow, kev and lev in p004, p005. Claude judged: partial.' - paper: pmid41300849 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Syncope, characterized by a transient loss of consciousness resulting from cerebral hypoperfusion, occurs in approximately 20% of patients with POTS [4]. However, it is generally considered an uncommon manifestation in this population, suggesting that syncope may rarely be a direct consequence of POTS [4]. note: 'Found by winnow, kev and lev in p003, p041. Claude judged: partial.' - paper: pmid41020219 cited: true text: full license: by verdict: partial section: 1 Introduction quote: In severe cases, the peripheral vasculature resistance is unable to compensate fully, resulting in a reduction in effective circulation and varying degrees of cerebral hypoperfusion. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid39875497 cited: true text: full license: by verdict: partial section: Abstract quote: Cerebral hypoperfusion is prevalent in those with POTS and cognitive dysfunction even whilst supine, contributing to reduced quality of life. note: 'Found by winnow, kev and lev in p001, p006, p011. Claude judged: partial.' - paper: pmid35689118 cited: true text: full license: by verdict: partial section: Discussion quote: Brain fog has been described to impede cognitive performance in patients with POTS, and the cause of brain fog has been attributed to a reduction in cerebral blood flow [77]. Accordingly, cerebral hypoperfusion may not only be linked to fatigue but also to the cognitive deficits seen in patients with POTS, with the cognitive decline observed being attributed to excessive levels of synaptic norepinephrine [78]. note: 'Found by winnow, kev and lev in p045, p010, p042. Claude judged: partial.' - paper: pmid35463901 cited: true text: full license: by verdict: partial section: Introduction quote: POTS syndrome is caused by cerebral hypoperfusion, in which the symptoms include lightheadedness, syncope, palpitations, and fatigue. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid33777484 cited: true text: full license: by verdict: partial section: Methods > Criterion for diagnosing orthostatic intolerance quote: Orthostatic intolerance (OI) is the umbrella term for a heterogeneous group of disorders of hemodynamic regulation characterized by excessive pooling of blood in the dependent areas of the body during upright posture, resulting in insufficient cerebral perfusion, which triggers symptoms typically relieved by recumbency. Both POTS and NCS patients have OI. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid33280488 cited: true text: full license: by-nc-nd verdict: partial section: Abstract > Methods and Results quote: The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (−7.8% versus −1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). note: 'Found by winnow, kev and lev in p002, p003, p012. Claude judged: partial.' - paper: pmid33050553 cited: true text: full license: by verdict: partial section: 4. Discussion quote: In the present study, a significantly higher reduction in cerebral blood flow was found in severe ME/CFS patients with POTS compared to severe ME/CFS patients without a history of POTS. note: 'Found by winnow, kev and lev in p001, p014, p018. Claude judged: partial.' - paper: pmid25002851 cited: true text: full license: by verdict: partial section: Abstract quote: Decreased upright cerebral blood flow (CBF) with hyperpnea and hypocapnia is seen in a minority of patients with postural tachycardia syndrome (POTS). More often, CBF is not decreased despite upright neurocognitive dysfunction. note: 'Found by winnow, kev and lev in p001, p003, p035. Claude judged: partial.' - paper: pmid22156614 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22156614. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - post_vaccination_onset - associated_with - pots papers: 19 evidence: - paper: pmid40729147 cited: true text: full license: by verdict: supports section: Abstract quote: This severe side effect indicates that providers need to be aware of this strong association of HPV vaccinations and POTS. note: 'Found by winnow, kev and lev in p009, p017, p001. Claude judged: supports.' - paper: pmid35870086 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p015, p002. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Discussion quote: De novo POTS is noted in a number of cases post-vaccination of HPV. One case report noted that there is a possible temporal relationship between the vaccination of Gardasil and onset of POTS [7,10]. note: 'Found by winnow, kev and lev in p012, p001, p008. Claude judged: supports.' - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: Among these, Postural Orthostatic Tachycardia Syndrome (POTS) has garnered attention due to reported cases following COVID-19 vaccination [2]. note: 'Found by winnow, kev and lev in p001, p006, p008. Claude judged: partial.' - paper: pmid39200375 cited: true text: full license: by verdict: partial section: 3. POTS Etiology and Its Complexity quote: The onset of POTS is frequently linked to triggers, such as long COVID-19, the human papillomavirus (HPV) vaccine, infections, or trauma, which can subsequently lead to immunological changes. note: 'Found by winnow, kev and lev in p018, p014. Claude judged: partial.' - paper: pmid39109119 cited: true text: full license: by verdict: partial section: Introduction quote: For example, human papillomavirus (HPV) vaccination programs have demonstrably reduced HPV infection rates, but concerns regarding rare vaccine adverse events (VAEs), such as POTS, have emerged [5,6,7]. There is also mounting evidence that suggests that coronavirus-2019 (COVID) infection and its vaccination protocols can induce autonomic dysfunction, including POTS and inappropriate sinus tachycardia (IST) [8,9,10]. note: 'Found by winnow, kev and lev in p012, p001, p003. Claude judged: partial.' - paper: pmid38176772 cited: true text: full license: none verdict: partial section: Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38176772. Found by winnow, kev and lev in p013, p025, p026. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid37654428 cited: true text: full license: by verdict: partial section: 10. POTS and vaccination quote: In a cohort of 2,84,592 COVID-19-vaccinated individuals, using a sequence–symmetry analysis, the odds of receiving the diagnosis of POTS 90 days after vaccination compared with 90 days before vaccination was 1.33 (1.25–1.41). The risk for POTS-related diagnoses was 5.35 (5.05–5.68) times higher after SARS-CoV-2 infection than after vaccination. note: 'Found by winnow, kev and lev in p001, p034, p035. Claude judged: partial.' - paper: pmid37650075 cited: true text: full license: by-nc verdict: partial section: Abstract > Background quote: It has been described after coronavirus disease-19 (COVID-19) as well as after COVID-19 vaccination. note: 'Found by winnow, kev and lev in p003, p012, p001. Claude judged: partial.' - paper: pmid37303827 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37303827. Found by winnow, kev and lev in p001, p002, p009. Claude judged: partial.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: POTS-like symptoms following COVID-19 vaccination quote: We identified 18 cases of reported POTS following COVID-19 vaccination from the available literature (Table 1). note: 'Found by winnow, kev and lev in p016, p017, p002. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports quote: Contemporary literature indicates potential links between viral infections and vaccines (particularly HPV) with the development of POTS.14,35,36 note: 'Found by winnow, kev and lev in p021, p022. Claude judged: partial.' - paper: pmid36530759 cited: true text: full license: none verdict: partial section: Expert opinion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36530759. Found by winnow, kev and lev in p008, p001, p004. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Discussion quote: However, POTS can be precipitated by immunologic stressors such as viral infection or vaccination [3]. Notably, reports of adult cases of new-onset POTS after COVID-19 mRNA vaccination have been emerging [12-15]. note: 'Found by winnow, kev and lev in p014, p002, p004. Claude judged: partial.' - paper: pmid35937046 cited: true text: full license: by verdict: partial section: Postural orthostatic tachycardia syndrome and its possible effect on LQTS quote: Postural orthostatic tachycardia syndrome (POTS) is another rare condition that may result from COVID-19 vaccination, supported by at least 2 case reports.23,24 note: 'Found by winnow, kev and lev in p012, p002, p011. Claude judged: partial.' - paper: pmid35891154 cited: true text: full license: by verdict: partial section: 4. Conclusions quote: While we cannot imply causality, the initial onset of POTS symptoms was closely linked in time to administration of the COVID-19 vaccination, similar to previously reported cases of POTS after COVID-19 vaccination. note: 'Found by winnow, kev and lev in p018, p001, p004. Claude judged: partial.' - paper: pmid35062788 cited: true text: full license: by verdict: partial section: 7. Conclusions quote: POTS has been reported to occur after vaccination with Gardasil. note: 'Found by winnow, kev and lev in p001, p007, p023. Claude judged: partial.' - paper: pmid24102827 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24102827. Found by winnow, kev and lev in p002, p004. Claude judged: partial.' - edge: - systemic_autoimmune_disease - associated_with - pots papers: 19 evidence: - paper: pmid41952073 cited: true text: full license: by verdict: supports section: Discussion quote: Additionally, autoimmune conditions such as asthma [32], Hashimoto's disease [33], Raynaud's syndrome [34], and Sjögren's syndrome [35] are more prevalent in POTS patients compared to the general population. note: 'Found by winnow, kev and lev in p030, p032, p036. Claude judged: supports.' - paper: pmid41446482 cited: true text: full license: by verdict: supports section: Discussion quote: Amongst them, chronic diabetes mellitus is the most common disease related to POTS [19]. Frequent associations include Hashimoto’s thyroiditis, Sjogren’s syndrome, antiphospholipid syndrome, systemic lupus erythematosus (lupus), and rheumatoid arthritis [19]. note: 'Found by winnow, kev and lev in p084, p003, p009. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Autoimmunity > Comorbidity with undifferentiated connective tissue disease quote: POTS and OCADs are commonly comorbid with other autoimmune disorders, with the most common being Hashimoto’s thyroiditis (Blitshteyn, 2015). Their association with Sjögren’s syndrome, antiphospholipid syndrome, and celiac disease has also been reported (Schofield et al., 2014; Penny et al., 2016; Mannan and Pain, 2023). note: 'Found by winnow, kev and lev in p015, p031, p017. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 1. Introduction quote: Furthermore, 20% of POTS patients have a diagnosis of a coexisting autoimmune disease, including but not limited to Hashimoto’s thyroiditis, celiac disease, Sjogren’s disease, rheumatoid arthritis, and systemic lupus erythematosus [5,6,7]. note: 'Found by winnow, kev and lev in p004, p030. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Support for an autoimmune mechanism in POTS and other forms of stress quote: 'There is a compelling association between POTS and autoimmunity: POTS is associated with a higher-than-expected frequency of defined autoimmune disorders. One cohort had positive anti-nuclear antibodies in 25% patients and a concurrent autoimmune diagnosis in 20% [43].' note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid36908200 cited: true text: full license: none verdict: supports section: 'Discussion: > Interpretation: > Implications for Clinical Care:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36908200. Found by winnow, kev and lev in p042, p011, p015. Claude judged: supports.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: A review of autoimmunity in POTS by Ref. [5] found that “patients with POTS have a higher than expected frequency of defined autoimmune disorders such as multiple sclerosis, lupus, Sjögren syndrome or celiac disease”. note: 'Found by winnow, kev and lev in p001, p003, p021. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Results > Autoimmmune Disorders quote: Approximately 20% of patients with POTS have comorbid autoimmune disorders, including Hashimoto’s thyroiditis, rheumatoid arthritis, lupus, APS, Sjogren’s syndrome and celiac disease.43,44 note: 'Found by winnow, kev and lev in p033, p017. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p006. Claude judged: supports.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: supports section: What is the pathophysiology of POTS? quote: Many patients describe a postviral onset,29–32 and 15%–20% of patients with POTS report a history of an autoimmune disorder such as Hashimoto thyroiditis, rheumatoid arthritis or Sjögren syndrome.4 note: 'Found by winnow, kev and lev in p018, p021. Claude judged: supports.' - paper: pmid35156619 cited: true text: full license: by-nc verdict: supports section: Introduction > Discussion quote: In some autoimmune conditions, POTS was described and includes systemic lupus erythematosus, Sjögren’s syndrome, multiple sclerosis, Raynaud’s phenomenon, and ASIA syndrome.11–15 note: 'Found by winnow, kev and lev in p012. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Antibodies and immunology of POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p022. Claude judged: supports.' - paper: pmid34055446 cited: true text: full license: by verdict: supports section: 3. Discussion quote: Although POTS is most commonly caused by dysfunctional regulation of blood pressure, there is an association with autoimmune conditions. Among the most common are rheumatoid arthritis and Sjogren's disease [5]. note: 'Found by winnow, kev and lev in p011. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: A study of 100 consecutive patients with POTS found that 31% of patients had 1 or more antibody markers and 20% had comorbid autoimmune disorders such as Hashimoto's thyroiditis, rheumatoid arthritis, or systemic lupus erythematosus.35 Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Discussion quote: Secondary forms of POTS occur in association with other disorders, most commonly diabetes mellitus. Other conditions include amyloidosis, sarcoidosis, alcoholism, systemic lupus erythematosus, Sjögren’s syndrome, heavy-metal intoxication, joint hypermobility syndrome, pure autonomic failure, multiple-system atrophy and paraneoplastic syndrome [7]. note: 'Found by winnow, kev and lev in p017. Claude judged: supports.' - paper: pmid42299385 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: First, the patient had SS manifested not only by thickening of the skin but also by vascular involvement in the form of migraine, POTS and Raynaud’s syndrome. Each of these manifestations has been described separately along with SS (8-10). note: 'Found by winnow, kev and lev in p007, p003, p012. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Primary Postural Orthostatic Tachycardia Syndrome and Pathophysiologic Mechanisms quote: Patients with autoimmune-related POTS may also present with autoimmune disorders as comorbidities. note: 'Found by winnow, kev and lev in p011, p058. Claude judged: partial.' - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: Patients with systemic autoimmune diseases may be at slightly increased risk for developing a neuropathic POTS phenotype - for instance, Sjogren’s syndrome is diagnosed at higher rates among POTS patients who have reduced IENFD [26]. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid33244220 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Sjogren’s syndrome (SS) is well characterized across neurology and rheumatology journals to be associated with both impaired autonomic function and postural orthostasis. note: 'Found by winnow, kev and lev in p004, p006, p032. Claude judged: partial.' - edge: - deconditioning_evidence - associated_with - pots papers: 15 evidence: - paper: pmid41357159 cited: true text: full license: none verdict: supports section: Discussion > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41357159. Found by winnow, kev and lev in p036, p010, p039. Claude judged: supports.' - paper: pmid40538940 cited: true text: full license: by verdict: supports section: Introduction quote: Deconditioning is considered to be closely related to PoTS (13, 14). note: 'Found by winnow, kev and lev in p007, p008, p009. Claude judged: supports.' - paper: pmid36000435 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: POTS has been associated with conditions causing peripheral autonomic denervation and connective tissue disorders (Joint hypermobility syndrome, Ehlers‐Danlos syndrome), chronic fatigue syndrome, autoimmune disorders, and deconditioning. note: 'Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid35557616 cited: true text: full license: by verdict: supports section: Discussion quote: Evidence suggests that physical deconditioning is an important aspect of POTS syndrome and can worsen symptoms (50). In the case that we presented and in our retrospective cohort, both the symptoms from PANS and POTS often lead to inactivity and deconditioning, and this deconditioning may further contribute to POTS. note: 'Found by winnow, kev and lev in p034. Claude judged: supports.' - paper: pmid31802934 cited: true text: full license: by-nc verdict: supports section: 'Challenge I: Complexities And Misunderstandings' quote: Diagnosis is further complicated by the fact that patients sometimes present with POTS as well as a concurrent diagnosis of deconditioning.1 The presence of deconditioning is considered a differential diagnosis (i.e., weighing the probability of one diagnosis versus the other diagnosis when they present with similar clinical features) for POTS and 70% of youth present with a concurrent diagnosis of deconditioning,1 making it difficult for clinical providers to name POTS as the primary diagnosis. note: 'Found by winnow, kev and lev in p012, p006, p030. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.8 Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Physical deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p030. Claude judged: supports.' - paper: pmid25980576 cited: true text: full license: none verdict: supports section: 'Section 1: Postural Tachycardia Syndrome Definition > Physiology > Deconditioning' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25980576. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid25168872 cited: true text: full license: by verdict: supports section: Introduction quote: Many patients with POTS limit physical activity whether due to pervasive fatigue and malaise or difficulty from orthostatic intolerance, presumably the reason why the majority of patients with POTS are deconditioned. Parsaik et al. (2012) found peak oxygen uptake () <85% predicted value in 90% of patients with POTS. note: 'Found by winnow, kev and lev in p004, p005, p019. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Exercise Physiology, Deconditioning, and POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p059, p061, p028. Claude judged: supports.' - paper: pmid24386408 cited: true text: full license: by verdict: supports section: Discussion quote: A recent study drew attention to the presence of deconditioning in POTS patients [28]. While the present data do not help disentangle the interaction between deconditioning and POTS, the presence of these levels of fatigue provides a possible explanation for the observed deconditioning and suggests that deconditioning may be present irrespective of POTS etiology. note: 'Found by winnow, kev and lev in p033, p034. Claude judged: supports.' - paper: pmid34265539 cited: true text: full license: none verdict: partial section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p030, p028. Claude judged: partial.' - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p026, p040. Claude judged: partial.' - paper: pmid28286774 cited: true text: full license: by verdict: partial section: 4. Discussion quote: POTS and OI have been frequently described in chronic fatigue syndrome and fibromyalgia, a fact that suggests that these conditions may share deconditioning. note: 'Found by winnow, kev and lev in p026. Claude judged: partial.' - paper: pmid25483980 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p027, p025. Claude judged: partial.' - edge: - small_fiber_neuropathy_dx - associated_with - pots papers: 15 evidence: - paper: pmid41301791 cited: true text: full license: by verdict: supports section: 3. Presyncope and Autonomic Dysfunction quote: Presyncope is also common in patients with small fiber neuropathy, which is one of the most common comorbidities of POTS and Long COVID [13,14]. note: 'Found by winnow, kev and lev in p008. Claude judged: supports.' - paper: pmid40271232 cited: true text: full license: by verdict: supports section: Conclusions quote: The relationship between POTS and SFN is well-established, but the diagnosis of SFN is currently either clinical or through skin punch biopsy. note: 'Found by winnow, kev and lev in p008, p036, p001. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: 'In addition to elevated autoimmune and inflammatory markers in POTS patients [45] and a higher prevalence of autoimmune disorders [42], POTS frequently co-occurs with a range of other conditions that have inflammatory underpinnings, such as: Small Fiber Neuropathy (SFN), characterized by damage to small nerve fibers and inflammatory processes [46]; Mast Cell Activation Syndrome (MCAS), involving excessive inflammatory mediator release [47]; Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME), associated with immune dysregulation and chronic inflammation [48]; and infections such as Lyme disease [49].' note: 'Found by winnow, kev and lev in p013, p015. Claude judged: supports.' - paper: pmid38537312 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38537312. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Neuropathy: It is estimated that up to half of the POTS cases have some form of small-fiber neuropathy, resulting in dysautonomia.' note: 'Found by winnow, kev and lev in p013. Claude judged: supports.' - paper: pmid33459162 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33459162. Found by winnow, kev and lev in p003, p001. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.1 Partial Sympathetic Neuropathy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Autoimmunity > Association with autonomic neuropathy quote: However, a non-length-dependent or patchy distribution of small fiber neuropathy can also occur, especially in conjunction with systemic autoimmune disorders (Gemignani et al., 2022). note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - paper: pmid39852767 cited: true text: full license: by verdict: partial section: 2. Case Presentation quote: However, an autoimmune basis of post-COVID POTS was evident given a positive ANA, comorbid SFN, and post-infectious onset of symptomatology. note: 'Found by winnow, kev and lev in p005, p003, p007. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Small Fiber Neuropathy and Complex Regional Pain Syndrome quote: SFN is suspected to contribute to the underlying pathologies of many different conditions, including POTS, CFS, complex regional pain syndrome (CRPS), and fibromyalgia, among others, and overlaps considerably with CPRS.[30] note: 'Found by winnow, kev and lev in p027, p028, p030. Claude judged: partial.' - paper: pmid37968647 cited: true text: full license: by verdict: partial section: Introduction quote: Small fiber neuropathy (SFN) has been suggested to be a possible mediator of POTS [16]. SFN can affect both autonomic and sensory fibers [17]. note: 'Found by winnow, kev and lev in p004, p009. Claude judged: partial.' - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Abstract quote: 'Conclusion: A subset of patients with postural orthostatic tachycardia syndrome have evidence of small fiber neuropathy.' note: 'Found by winnow, kev and lev in p004, p037, p006. Claude judged: partial.' - paper: pmid33764697 cited: true text: full license: by verdict: partial section: Introduction quote: Furthermore, in some patients with neuropathic POTS, intraepidermal nerve fiber density is decreased, providing objective support for a small fiber neuropathy in these POTS patients. note: 'Found by winnow, kev and lev in p007, p003, p027. Claude judged: partial.' - paper: pmid24647968 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24647968. Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid16943900 cited: true text: full license: by verdict: partial section: Pathophysiology of POTS > Neuropathic POTS quote: Yet some of them have a form of dysautonomia, with preferential denervation of sympathetic nerves innvervating the lower limbs [22-24]. There have been several findings consistent with this hypothesis. note: 'Found by winnow, kev and lev in p024. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - postinfectious_evidence papers: 12 evidence: - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Wallukat et al. conducted a study in which 31 patients with POTS and COVID-19 were examined. All patients had positive autoantibodies ranging from two to seven. note: 'Found by winnow, kev and lev in p006, p027, p034. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Autoimmunity: Many patients, after a viral illness, develop POTS symptoms, which are suspected to be due to an autoimmune response.' note: 'Found by winnow, kev and lev in p012, p001. Claude judged: supports.' - paper: pmid25087056 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25087056. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Autoimmunity > Autoimmunity in Long COVID quote: G protein-coupled receptor antibodies, including against alpha- and beta-adrenergic antibodies and muscarinic antibodies, previously identified in patients with POTS, as well as autoantibodies to antinuclear and extractable nuclear antigens, have also been found in patients with Long COVID (Wallukat et al., 2021; El-Rhermoul et al., 2023; Son et al., 2023). note: 'Found by winnow, kev and lev in p001, p013, p019. Claude judged: partial.' - paper: pmid39200375 cited: true text: full license: by verdict: partial section: 3. POTS Etiology and Its Complexity quote: The onset of POTS is frequently linked to triggers, such as long COVID-19, the human papillomavirus (HPV) vaccine, infections, or trauma, which can subsequently lead to immunological changes. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: Although the exact pathophysiology mechanism is unclear, it is thought that the combination of autoimmunity, relative central hypovolemia, small fiber neuropathy, hyperadrenergic stimulation, and pro-inflammatory cytokine production (i.e., cytokine storm) is a critical factor in POTS and COVID-19 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013. Claude judged: partial.' - paper: pmid29687025 cited: true text: full license: by-nc-nd verdict: partial section: Results > Clinical assessment of autonomic function in patients with seropositive POTS in second analysis quote: Antecedent infections were reported in five patients (50%) with seropositive POTS, but there were no differences between seropositive and seronegative patients. note: 'Found by winnow, kev and lev in p001, p014. Claude judged: partial.' - paper: pmid28738696 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28738696. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Pathophysiology of POTS > Autoimmune/Autoantibodies quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p031. Claude judged: partial.' - paper: pmid19058765 cited: true text: full license: none verdict: partial section: Postural Tachycardia Syndrome (POTS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 19058765. Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - systemic_autoimmune_disease papers: 12 evidence: - paper: pmid41952073 cited: true text: full license: by verdict: partial section: Discussion quote: 'Moreover, POTS is also associated with a higher prevalence of atopic conditions and autoimmune disorders compared to the general population: Asthma (20.3% (95% CI 19.1–21.5) in POTS vs. 3.3% (95% CI 2.9–3.8) in the general population [32]), Hashimoto''s disease (8.3% (95% CI 4.1–16.0) vs. 7.5% (95% CI 5.7–9.6) [33]), Raynaud''s syndrome (15.5% (95% CI 14.4–16.7) vs. 4.85% (95% CI 2.1–8.7) [34]), and Sjögren''s syndrome (4.7% (95% CI 1.7–12.2) versus 0.06% (95% CI 0.04–0.08) [35]).' note: 'Found by winnow, kev and lev in p030, p036. Claude judged: partial.' - paper: pmid41446482 cited: true text: full license: by verdict: partial section: Discussion quote: In our study, patients also had autoimmune diseases, which were Sjogren’s syndrome, Crohn’s disease, psoriatic arthritis, and multiple sclerosis. Research is underway to establish a link between certain autoantibodies, such as G-protein-coupled adrenergic receptors and muscarinic cholinergic receptor antibodies found in elevated levels in POTS, which corresponds to the theory that POTS may have an immune-mediated pathogenesis [19]. note: 'Found by winnow, kev and lev in p084, p009. Claude judged: partial.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Autoimmunity > Comorbidity with undifferentiated connective tissue disease quote: POTS and OCADs are commonly comorbid with other autoimmune disorders, with the most common being Hashimoto’s thyroiditis (Blitshteyn, 2015). Their association with Sjögren’s syndrome, antiphospholipid syndrome, and celiac disease has also been reported (Schofield et al., 2014; Penny et al., 2016; Mannan and Pain, 2023). note: 'Found by winnow, kev and lev in p015, p031, p018. Claude judged: partial.' - paper: pmid38673062 cited: true text: full license: by verdict: partial section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.5. Antiphospholipid and Antinuclear Autoantibodies quote: Blitshteyn performed a retrospective review of POTS patients to evaluate comorbid autoimmune disorders and the presence of AAbs. Autoimmune disorders were present in 20/100 patients, including Hashimoto’s thyroiditis (11/100), antiphospholipid syndrome (5/100), rheumatoid arthritis (4/100), celiac disease (3/100), systemic lupus erythematosus (2/100), and Sjögren’s syndrome (2/100). note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid36816268 cited: true text: full license: by-nc-nd verdict: partial section: Introduction quote: Patients with one AD are often more prone to others. A review of autoimmunity in POTS by Ref. [5] found that “patients with POTS have a higher than expected frequency of defined autoimmune disorders such as multiple sclerosis, lupus, Sjögren syndrome or celiac disease”. note: 'Found by winnow, kev and lev in p003, p074, p022. Claude judged: partial.' - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: Some cases of neuropathic POTS are thought to arise from immune-mediated neuropathy. In this cohort, there was a trend toward higher rates of comorbid autoimmune disease among patients with evidence of SFN compared to patients without, though the difference was not statistically significant. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Selected Etiology: Autoimmune > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p068. Claude judged: partial.' - paper: pmid35156619 cited: true text: full license: by-nc verdict: partial section: Introduction > Discussion quote: In some autoimmune conditions, POTS was described and includes systemic lupus erythematosus, Sjögren’s syndrome, multiple sclerosis, Raynaud’s phenomenon, and ASIA syndrome.11–15 note: 'Found by winnow, kev and lev in p003, p012. Claude judged: partial.' - paper: pmid34144933 cited: true text: full license: none verdict: partial section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p013, p022. Claude judged: partial.' - paper: pmid34055446 cited: true text: full license: by verdict: partial section: 3. Discussion quote: A pathogenesis of POTS includes an autoimmune basis with a high prevalence of positive ANA and comorbid autoimmune disorders [3]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid31498378 cited: true text: full license: none verdict: partial section: Medical Causes and Contributors quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 31498378. Found by winnow, kev and lev in p012, p022. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: A study of 100 consecutive patients with POTS found that 31% of patients had 1 or more antibody markers and 20% had comorbid autoimmune disorders such as Hashimoto's thyroiditis, rheumatoid arthritis, or systemic lupus erythematosus.35 Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: partial.' - edge: - gi_dysmotility - associated_with - hypermobility_heds papers: 11 evidence: - paper: pmid42509985 cited: true text: full license: by verdict: supports section: 3. Discussion > 3.1. Dysautonomia and the Rationale for Prokinetic Bridge Therapy quote: 'Patient 3 illustrates a further layer of this pathophysiology: the overlap between POTS, hypermobile Ehlers–Danlos syndrome (hEDS), and disorders of gut–brain interaction. Connective tissue laxity in hEDS is increasingly recognized as a contributor to GI dysmotility and visceral hypersensitivity through mechanisms distinct from, but overlapping with, autonomic dysregulation [18].' note: 'Found by winnow, kev and lev in p027, p036. Claude judged: supports.' - paper: pmid41858767 cited: true text: full license: by-nc-nd verdict: supports section: Introduction quote: Gastrointestinal symptoms in POTS and HSD/hEDS occur frequently, both as functional gastrointestinal disorders and as more severe intestinal dysmotility disorders (10-12). note: 'Found by winnow, kev and lev in p004, p001. Claude judged: supports.' - paper: pmid39543811 cited: true text: full license: by verdict: supports section: Body quote: 'Two specific DGBI clusters exist in the hEDS/HSD cohort: those with mainly functional foregut disorders (FFD) with overlapping irritable bowel syndrome (hEDS/HSD + FFD + IBS) and those with predominantly IBS (hEDS/HSD + IBS).' note: 'Found by winnow, kev and lev in p003, p032, p005. Claude judged: supports.' - paper: pmid34765384 cited: true text: full license: by verdict: supports section: Discussion quote: One retrospective study found that both EDS III and POTS are independent risk factors for gastrointestinal (GI) symptoms, including GI dysmotility and gastroesophageal reflux disease [15]. note: 'Found by winnow, kev and lev in p006, p019. Claude judged: supports.' - paper: pmid32803794 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32803794. Found by winnow, kev and lev in p003, p001, p004. Claude judged: supports.' - paper: pmid32489735 cited: true text: full license: by verdict: supports section: Conclusions quote: GI dysmotility among patients with hEDS is not uncommon and possibly underdiagnosed. note: 'Found by winnow, kev and lev in p054, p008, p012. Claude judged: supports.' - paper: pmid29891041 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29891041. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Results > Postural Tachycardia Syndrome, Gastrointestinal Symptoms, and related co-morbidities GI symptoms in Postural Tachycardia Syndrome and Ehlers-Danlos quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p016, p015, p028. Claude judged: supports.' - paper: pmid42691689 cited: true text: full license: none verdict: partial section: Autonomic system degenerations, generalized dysautonomia, and disorders of autonomic dysregulation > Postural orthostatic tachycardia syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42691689. Found by winnow, kev and lev in p044. Claude judged: partial.' - paper: pmid40387691 cited: true text: abstract license: none verdict: partial section: Abstract > Methods quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 40387691. Found by winnow, kev and lev in p002. Claude judged: partial.' - paper: pmid39268060 cited: true text: full license: by verdict: partial section: Abstract quote: Gastroparesis is a chronic disorder involving symptoms of delayed gastric emptying and may be closely associated with hEDS and POTS, and may be underreported. note: 'Found by winnow, kev and lev in p069, p071, p001. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - long_covid papers: 11 evidence: - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Autoimmunity quote: Similar to POTS, autoimmunity is considered to be one of the major mechanisms of Long COVID, with an associated increased risk, overall incidence and range of autoimmune conditions after SARS-CoV-2 infection.21,37 note: 'Found by winnow, kev and lev in p007, p012. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: supports section: Autoimmunity > Autoimmunity in Long COVID quote: G protein-coupled receptor antibodies, including against alpha- and beta-adrenergic antibodies and muscarinic antibodies, previously identified in patients with POTS, as well as autoantibodies to antinuclear and extractable nuclear antigens, have also been found in patients with Long COVID (Wallukat et al., 2021; El-Rhermoul et al., 2023; Son et al., 2023). The pro-inflammatory mediators, non-specific antibodies, and antibodies important to the function of the autonomic nervous system are thought to be implicated in the development of post-COVID autonomic disorders, such as POTS and OCADs (El-Rhermoul et al., 2023). note: 'Found by winnow, kev and lev in p001, p013, p019. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 3. Discussion > 3.2. Individualizing Treatment Plans quote: With evidence that many patients suffering from long COVID can develop autoimmune-mediated orthostatic intolerance, prompt recognition is important as it can expedite appropriate treatment [9]. note: 'Found by winnow, kev and lev in p006, p027, p047. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Long Covid—the new pandemic quote: Notable autoantibodies include functionally active autoantibodies to the GPCRs (including α1- and β2-adrenoceptors, angiotensin receptor, nociception-like opioid receptor and muscarinic M2-receptor) [11]. This is significant for the overlap with POTS [12] and autonomic nervous system. note: 'Found by winnow, kev and lev in p004, p009, p001. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 7. Diagnosis of Post-COVID Dysautonomia quote: PASC patients with POTS-like symptoms feature a high prevalence of circulating AAbs, at times with peculiar patterns [57] (Figure 1). note: 'Found by winnow, kev and lev in p038, p025. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: partial section: 3. POTS Etiology and Its Complexity quote: The mechanisms behind this association are not fully elucidated but may involve inflammation, microthrombi, and autoimmunity [59,60]. note: 'Found by winnow, kev and lev in p014, p019. Claude judged: partial.' - paper: pmid38900132 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38900132. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Recently, there was a surge in the incidence of POTS after the COVID-19 pandemic. Functional antibodies against different GPCRs have also been demonstrated in the serum of symptomatic post-COVID-19 patients.[23] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: Although the exact pathophysiology mechanism is unclear, it is thought that the combination of autoimmunity, relative central hypovolemia, small fiber neuropathy, hyperadrenergic stimulation, and pro-inflammatory cytokine production (i.e., cytokine storm) is a critical factor in POTS and COVID-19 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Abstract quote: The exact mechanisms of post-COVID-19 POTS are unclear. Still, different hypotheses have been given, including autoantibody production against autonomic nerve fibers, direct toxic effects of SARS-CoV-2, or sympathetic nervous system stimulation secondary to infection. note: 'Found by winnow, kev and lev in p012, p001. Claude judged: partial.' - paper: pmid36509178 cited: true text: full license: none verdict: partial section: Discussion > Hospitalization status quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36509178. Found by winnow, kev and lev in p037. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - mast_cell_activation papers: 10 evidence: - paper: pmid39109428 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39109428. Found by winnow, kev and lev in p024, p034, p035. Claude judged: supports.' - paper: pmid38526146 cited: true text: full license: by-nc-nd verdict: supports section: Abstract quote: A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. note: 'Found by winnow, kev and lev in p006, p001, p020. Claude judged: supports.' - paper: pmid37255928 cited: true text: full license: by verdict: supports section: Associations with mast cell activation disorders quote: These MCA/POTS patients had predominant flushing breathlessness, headache, lightheadedness, excessive diuresis, diarrhoea, nausea and vomiting, and had a marked hyperadrenergic orthostatic response, with higher noradrenaline levels and exaggerated blood pressure rise on standing compared with the POTS and control groups [95]. note: 'Found by winnow, kev and lev in p028. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mechanisms quote: These patients experience severe episodic flushing with sinus tachycardia.14 The patient will have a hyperadrenergic response to position change and an elevated urine methylhistamine during flushing episodes.14 note: 'Found by winnow, kev and lev in p014. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.5 Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p022. Claude judged: supports.' - paper: pmid26198889 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p029. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p018. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Pathophysiology of POTS > Mast Cell Activation quote: These patients often have a hyperadrenergic response to posture, with both orthostatic tachycardia and hypertension. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid15710782 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 15710782. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: partial section: Discussion quote: A patient with severe POTS, MCAS and SIBO responded to a combination of LDN, IVIg and antibiotic therapy. We theorise that pre-existing MCAS was the driving force for hyperadrenergic POTS in this patient. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - edge: - long_covid - associated_with - me_cfs papers: 10 evidence: - paper: pmid41859298 cited: true text: full license: by-nc verdict: supports section: Long COVID quote: Both ME/CFS and POTS are major phenotypes associated with Long COVID, and autonomic dysfunction is present in nearly 70% of patients with Long COVID, making it a major pathophysiologic mechanism.18,19 note: 'Found by winnow, kev and lev in p007, p013. Claude judged: supports.' - paper: pmid40627388 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: Despite the diverse symptoms in individual patients, studies have shown that many long COVID and ME/CFS sufferers share hallmark symptoms such as fatigue, postexertional malaise (PEM), unrefreshing sleep, orthostatic intolerance (OI), and cognitive dysfunction. These symptoms align with the 2015 Institute of Medicine (IOM) diagnostic criteria for ME/CFS (2, 3, 8, 14–17). note: 'Found by winnow, kev and lev in p004, p010, p032. Claude judged: supports.' - paper: pmid38600563 cited: true text: full license: by verdict: supports section: Background quote: Following acute SARS-CoV-2 infection, a subset of individuals continues to suffer from lingering symptoms very similar to those associated with ME/CFS. It has been estimated that about half of people presenting with long COVID at six months meet the case criteria for ME/CFS [7, 8]. note: 'Found by winnow, kev and lev in p006, p053. Claude judged: supports.' - paper: pmid36981522 cited: true text: full license: by verdict: supports section: Abstract quote: At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients. We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic. note: 'Found by winnow, kev and lev in p001, p003, p006. Claude judged: supports.' - paper: pmid36639608 cited: true text: full license: none verdict: supports section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p022, p024, p037. Claude judged: supports.' - paper: pmid36611357 cited: true text: full license: by verdict: supports section: 4. Discussion quote: Pairwise comparison of the average increase in heart rate relative to basal values between the cohorts at each minute of the active standing test showed that in ME/CFS that developed after COVID-19, there is a more pronounced increase in heart rate starting from the 6th minute of the test compared to the control group. This allowed us to assume that POTS is one of the key characteristics of ME/CFS of post-COVID genesis. note: 'Found by winnow, kev and lev in p035, p040, p046. Claude judged: supports.' - paper: pmid33996867 cited: true text: full license: by verdict: supports section: Introduction quote: In all three, ME/CFS symptoms were prominent from the outset, as were symptoms and signs of orthostatic intolerance, consistent with an early contribution of circulatory disturbances to the pathogenesis of symptoms, before the onset of physiological changes due to inactivity. The preliminary findings of this case series have the potential to inform the investigation and treatment of what has been termed “long COVID” (8) or post-COVID-19 ME/CFS. note: 'Found by winnow, kev and lev in p004, p006, p013. Claude judged: supports.' - paper: pmid41050528 cited: true text: full license: by-nc verdict: partial section: Case presentation quote: After a new COVID-19 infection in February 2021, he developed typical long COVID symptoms of dysautonomia, post-exertional malaise (PEM), and symptoms compatible with POTS. note: 'Found by winnow, kev and lev in p002, p009. Claude judged: partial.' - paper: pmid40883051 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: Our findings add to the hypothesized associations between ME/CFS and long COVID, often discussed together due to overlapping symptomatology and infectious etiopathogenesis.12,35, 36, 37 note: 'Found by winnow, kev and lev in p035. Claude judged: partial.' - paper: pmid35241011 cited: true text: full license: by verdict: partial section: Background quote: CFS/ME has been associated with several viruses, including the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV; 6), and has been recently garnering media attention as a post-acute consequence of SARS-CoV-2 infection. note: 'Found by winnow, kev and lev in p005. Claude judged: partial.' - edge: - hypovolemic_evidence - associated_with - pots papers: 9 evidence: - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 1 Introduction quote: Hypovolemia is one of the main pathological features in POTS [3,4,6,7]. POTS patients frequently experience hypovolemia, which may be caused by insufficient fluid intake and excessive fluid loss. note: 'Found by winnow, kev and lev in p003, p001, p008. Claude judged: supports.' - paper: pmid37435242 cited: true text: full license: by verdict: supports section: Discussion quote: Along with tachycardia with orthostatic intolerance, other symptoms can also accompany the syndrome. In the majority of patients, intravascular volume is reduced, thus leading to decreased venous return to the heart and causing reflex tachycardia and orthostatic intolerance. note: 'Found by winnow, kev and lev in p001, p005. Claude judged: supports.' - paper: pmid32655482 cited: true text: full license: by verdict: supports section: Pots Subtypes in Children and Adolescents > Hypovolemic POTS quote: Hypovolemia could be observed in nearly 30% of POTS patients, as Thieben et al. estimated (16). In our experience, over fifty percent of children and adolescents with POTS have low blood volume (5). note: 'Found by winnow, kev and lev in p010, p011, p018. Claude judged: supports.' - paper: pmid23753844 cited: true text: full license: none verdict: supports section: Pathophysiology of POTS > Hypovolemia & Blood Volume Regulation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23753844. Found by winnow, kev and lev in p028, p015, p020. Claude judged: supports.' - paper: pmid16262605 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 16262605. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid40027266 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: POTS is an autonomic disorder characterized by excessive reflex sympathetic excitation triggered by orthostatic stress. The pathophysiology remains elusive; however, central hypovolemia has been identified as the mechanism leading to venous pooling, hypovolemia, deconditioning, and hyperadrenergic state. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid34268642 cited: true text: full license: none verdict: partial section: Autonomic Disorders and Headache quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34268642. Found by winnow, kev and lev in p015, p019. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Discussion quote: A subset of patients with POTS has low levels of standing plasma renin activity, aldosterone, and blood volume as compared to normovolemic patients [10]. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid25483980 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - differential_syncope_oh - associated_with - pots papers: 7 evidence: - paper: pmid41300849 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Syncope, characterized by a transient loss of consciousness resulting from cerebral hypoperfusion, occurs in approximately 20% of patients with POTS [4]. note: 'Found by winnow, kev and lev in p003, p040, p041. Claude judged: partial.' - paper: pmid36518687 cited: true text: full license: by verdict: partial section: Abstract > Results quote: Patients with vasovagal syncope (VVS) coexisting with postural orthostatic tachycardia syndrome (POTS) were more likely to take pharmacological treatments than those with VVS or POTS only (χ2 = 41.696, P < 0.01). note: 'Found by winnow, kev and lev in p031, p004, p005. Claude judged: partial.' - paper: pmid36252987 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: The importance of diagnosing BASCULE syndrome lies in its association with a spectrum of orthostatic intolerance conditions, including syncope, orthostatic hypotension and POTS (a condition associated with mast cell activation and hypermobility spectrum disorders).2,3 note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Abstract > Conclusion quote: We have to keep this possibility in young patients of transient loss of consciousness because it may coexist with NCS. note: 'Found by winnow, kev and lev in p002, p005, p014. Claude judged: partial.' - paper: pmid31250563 cited: true text: full license: by verdict: partial section: Introduction quote: VVS can occur in patients diagnosed with the postural tachycardia syndrome (POTS). The incidence of VVS in POTS patients is believed to be about 30%, similar to its incidence in the general population (Raj 2006; Kimpinski et al. 2012), which is consistent with our experience. note: 'Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - paper: pmid30838497 cited: true text: full license: none verdict: partial section: Head-up tilt in the diagnostic evaluation of syncope quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30838497. Found by winnow, kev and lev in p070. Claude judged: partial.' - paper: pmid26198889 cited: true text: full license: none verdict: partial section: Disorders Overlapping with POTS > Vasovagal Syncope (VVS) quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 26198889. Found by winnow, kev and lev in p020, p017. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - mast_cell_activation papers: 6 evidence: - paper: pmid41282714 cited: true text: full license: by verdict: supports section: Introduction quote: The frequent co-occurrence in patients with hEDS of mast cell activation syndrome (MCAS), a poorly defined disorder marked by episodic hypersensitivity and gastrointestinal symptoms, adds additional diagnostic ambiguity[16–19]. note: 'Found by winnow, kev and lev in p046, p009, p045. Claude judged: supports.' - paper: pmid40843452 cited: true text: full license: by-nc-nd verdict: supports section: Discussion > Small Fiber Neuropathy quote: An association between hEDS and mast cell disorders has been made in previous studies56 but the true prevalence of mast cell disorders in hEDS remains unclear due to differing clinical criteria used in the definition of the mast cell disorders.57, 58, 59 In our study, 61% of patients used anti-histamine medications, and 41% had a history of symptoms associated with mast cell activation syndrome. note: 'Found by winnow, kev and lev in p049. Claude judged: supports.' - paper: pmid40352770 cited: true text: full license: by verdict: supports section: Introduction quote: It has been recognized for more than two decades, but only recently become well-established in the past five years, that the conditions of orthostatic intolerance with an underlying contributing etiology of autonomic neuro-immune axis dysfunction (sometimes referred to generally as dysautonomia), what we term here, orthostatic intolerance syndromes (OIS), as well as joint hypermobility disorders (JHD), and mast cell activation syndrome (MCAS) co-segregate in patients who have these disorders (1–5). note: 'Found by winnow, kev and lev in p012, p001, p005. Claude judged: supports.' - paper: pmid39931100 cited: true text: full license: by verdict: supports section: Introduction quote: Notably, individuals with symptoms of hEDS often present with concomitant autonomic and immune dysfunctions such as postural orthostatic tachycardia syndrome (POTS) and mast cell activation disorder (MCAD), respectively, whose associations with connective tissue and joint fragility are well documented (10, 19). note: 'Found by winnow, kev and lev in p003, p006, p024. Claude judged: supports.' - paper: pmid38003876 cited: true text: full license: by verdict: partial section: Abstract quote: All eight patients were subsequently diagnosed with mast cell activation syndrome; six had comorbid autonomic disorders, the most common being postural orthostatic tachycardia syndrome; and four had hypermobile Ehlers-Danlos syndrome. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What other conditions commonly occur in patients with POTS? quote: Hypermobility spectrum disorder may co-occur with mast cell activation disorder in some patients with POTS. note: 'Found by winnow, kev and lev in p018. Claude judged: partial.' - edge: - fibromyalgia - associated_with - pots papers: 6 evidence: - paper: pmid42691689 cited: true text: full license: none verdict: supports section: Autonomic system degenerations, generalized dysautonomia, and disorders of autonomic dysregulation > Postural orthostatic tachycardia syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42691689. Found by winnow, kev and lev in p044. Claude judged: supports.' - paper: pmid40546538 cited: true text: full license: by verdict: supports section: Discussion quote: In our clinic, we often see POTS patients experience pain through common comorbidities like fibromyalgia (FM), headaches, and migraines. FM is a pain-related comorbidity [13]. note: 'Found by winnow, kev and lev in p033. Claude judged: supports.' - paper: pmid38348221 cited: true text: full license: by verdict: supports section: 1 Introduction quote: POTS frequently presents with chronic comorbidities or conditions that are unrelated to orthostatic intolerance, such as migraine, fibromyalgia, chronic fatigue, and allergic disorders (Liao et al., 2017; Chelimsky and Chelimsky, 2018). note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid29876157 cited: true text: full license: by verdict: supports section: Review quote: Fibromyalgia, which is also a disease of young women, was found to be associated with POTS in a study [32-33]. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid26425598 cited: true text: full license: by verdict: supports section: Introduction quote: Such typical CFS symptoms that are overrepresented in POTS patients include migraine, incapacitating fatigue, fibromyalgia, unrefreshing sleep, and impaired memory or concentration. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: Body quote: Postural orthostatic tachycarda syndrome (POTS) has been documented in migraine [1] and fibromyalgia [2], which is defined when the orthostatic symptoms are associated with a heart rate (HR) increment of more than 30 beats per minute (bpm) or a standing HR of 120 bpm or more in the absence of postural hypotension [3]. note: 'Found by winnow, kev and lev in p001, p012, p002. Claude judged: supports.' - edge: - hyperadrenergic_evidence - associated_with - hypermobility_heds papers: 5 evidence: - paper: pmid41924132 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Additionally, heightened vascular distensibility promotes venous pooling in the extremities and may precipitate a maladaptive autonomic adrenergic response with associated dizziness and palpitations, as seen in POTS. note: 'Found by winnow, kev and lev in p008. Claude judged: partial.' - paper: pmid39301475 cited: true text: full license: by verdict: partial section: Relationship to post-infectious syndromes including long COVID quote: Adrenaline, a key effector hormone of the sympathetic nervous system, is elevated in hyperadrenergic POTS. It has been shown to inhibit the function of human fibroblasts and modulate the expression of local growth factors, thereby potentially explaining a mechanism of adrenaline-induced connective tissue dysfunction (29, 30). note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid35620060 cited: true text: full license: by-nc verdict: partial section: Patient 3 quote: Given her symptoms of flushing, anxiety, and faintness upon assuming an upright position, supine (685 pg/mL) and standing (1386 pg/mL) norepinephrine levels were assessed and suggested hyperadrenergic POTS. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid34510391 cited: true text: full license: none verdict: partial section: Overlap of Dysautonomia and Hypermobility Syndromes quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34510391. Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid25713509 cited: true text: full license: by verdict: partial section: Neurovisceral phenotypes > Joint hypermobility > Association with psychiatric disorder quote: In disorders that typically involve impaired collagen (present in blood vessels) such as joint hypermobility and postural tachycardia syndrome it is likely that reduced venous return during standing due to venous pooling or denervation causing low plasma volume may be responsible for a an increased sympathetic state–as the body attempts to compensate for these abnormalities—resulting in orthostatic intolerance and associated symptoms (Bohora, 2010; Benarroch, 2012; Mathias et al., 2012). note: 'Found by winnow, kev and lev in p009, p011. Claude judged: partial.' - edge: - long_covid - associated_with - neuropathic_evidence papers: 5 evidence: - paper: pmid39852767 cited: true text: full license: by verdict: supports section: 3. Discussion quote: 'POTS and SFN are comorbid conditions, with both being highly prevalent in patients with Long COVID: an estimated 30–75% of patients with Long COVID have POTS [6,7], and nearly 70% have autonomic dysfunction [8]. The prevalence of SFN in Long COVID is unknown, but appears to be similarly high and close to 70% based on small studies [9,10].' note: 'Found by winnow, kev and lev in p005, p013. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Introduction and background quote: SARS-CoV-2 can access multiple organ systems through the ACE-2 receptor [18]. Its pathophysiology is postulated to include virus- or immune-mediated damage to the autonomic nervous system. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid36938206 cited: true text: full license: by verdict: partial section: Discussion quote: We suspect a neuropathic cause of POTS in our patient that may be secondary to a viral cause, due to his history of infection with COVID-19. note: 'Found by winnow, kev and lev in p005, p001, p015. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: INTRODUCTION quote: Because viral infection can host various chronic neurological conditions, such as Guillain-Barre syndrome, POTS can possibly occur as a post-COVID-19 autonomic nerve involvement. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid36639608 cited: true text: full license: none verdict: partial section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - physical_trauma_onset - associated_with - pots papers: 5 evidence: - paper: pmid42369281 cited: true text: full license: by verdict: partial section: Links between trauma and nervous system dysregulation and autonomic symptom burden quote: These associations certainly do not prove a cause-effect relationship between trauma and POTS, nor are we proponents of such a simplistic explanation. However, the associations support a model in which continued activation of survival circuits bias the brain toward maladaptive persistent sympathetic activation with failure to restore healthy parasympathetic (vagal) dominance. note: 'Found by winnow, kev and lev in p020, p035. Claude judged: partial.' - paper: pmid40694349 cited: true text: full license: by verdict: partial section: Introduction quote: While concussion is the second leading trigger of pediatric postural orthostatic tachycardia syndrome (POTS),7 a chronic AD condition affecting approximately 1% of youths worldwide,8 the association of AD with concussion is poorly understood due to limited research and inconsistent AD definitions used across studies.9,10,11,12,13,14,15,16 note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid35647216 cited: true text: full license: by-nc verdict: partial section: Background quote: Moreover, concussion was found to be the second most common trigger preceding POTS onset in a group of 708 patients at a pediatric autonomic disorders clinic, second only to infection among the triggers assessed. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: 'Abstract > Summary of Key Points:' quote: Data recorded and entered into a database during clinic visits from a large pediatric institution indicate that 11.4% of individuals diagnosed with POTS report onset of symptoms within 3 months of sustaining a concussion. note: 'Found by winnow, kev and lev in p003, p012, p031. Claude judged: partial.' - paper: pmid20865679 cited: true text: abstract license: none verdict: partial section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20865679. Found by winnow, kev and lev in p001, p002, p003. Claude judged: partial.' - edge: - neuropathic_evidence - associated_with - small_fiber_neuropathy_dx papers: 5 evidence: - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 4. Pathophysiology of POTS > 4.1 Partial Sympathetic Neuropathy quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p015. Claude judged: supports.' - paper: pmid40271232 cited: true text: full license: by verdict: partial section: Introduction quote: In POTS patients with neuropathic symptoms, skin nerve biopsy can show decreased intraepidermal nerve fiber density (NFD) indicative of small fiber neuropathy (SFN) [19,20]. note: 'Found by winnow, kev and lev in p008, p036, p001. Claude judged: partial.' - paper: pmid37968647 cited: true text: full license: by verdict: partial section: Introduction quote: Small fiber neuropathy (SFN) has been suggested to be a possible mediator of POTS [16]. SFN can affect both autonomic and sensory fibers [17]. note: 'Found by winnow, kev and lev in p004, p009. Claude judged: partial.' - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: These patients with evidence of autonomic SFN are likely to have a neuropathic subtype of POTS, though evidence of one subtype does not rule out the presence of other subtypes, given the heterogeneity of the disorder. note: 'Found by winnow, kev and lev in p004, p033, p037. Claude judged: partial.' - paper: pmid33764697 cited: true text: full license: by verdict: partial section: Introduction quote: Furthermore, in some patients with neuropathic POTS, intraepidermal nerve fiber density is decreased, providing objective support for a small fiber neuropathy in these POTS patients. note: 'Found by winnow, kev and lev in p007, p003. Claude judged: partial.' - edge: - anxiety_depression - associated_with - long_covid papers: 4 evidence: - paper: pmid38510743 cited: true text: full license: by-nc-nd verdict: supports section: Long Covid syndrome, neuro-cardiologic complications and prognosis quote: A long Covid syndrome may be clinically manifested with orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), syncope, chest pain, dyspnea, palpitation, chronic fatigue syndrome, ‘brain fog’, memory, cognitive and sleep difficulties, anosmia, headache, signs of impaired cardiac and cerebral perfusion, depression and anxiety [57,59,60]. A higher prevalence of psychiatric syndromes - post-traumatic stress disorder (PTSD) (28 %), depression (31 %), anxiety (42 %), insomnia (40 %), and obsessive-compulsive (OS) symptoms (20 %) was also reported [61]. note: 'Found by winnow, kev and lev in p001, p026, p028. Claude judged: supports.' - paper: pmid34821709 cited: true text: full license: by verdict: supports section: 3. COVID-19 Infection and Dysautonomia quote: Recent evidence showed the significant burden of fatigue, symptoms of autonomic dysfunction, and mood disorders in the aftermath of COVID-19 infection, but reassuringly did not demonstrate pathological findings during investigations for autonomic function [33]. Fatigue is linked to the higher prevalence of anxiety and post-traumatic stress disorder in COVID-19 survivors [23,27,33,54], while somatic anxiety in patients with chronic fatigue has been directly associated with autonomic nervous system dysfunction [55]. note: 'Found by winnow, kev and lev in p013, p003. Claude judged: supports.' - paper: pmid39317338 cited: true text: full license: by-nc verdict: partial section: Abstract > Results quote: In comparison to the group without post COVID-19 long-term cardiovascular symptoms, the group with post COVID-19 long-term cardiovascular symptoms exhibited a significantly higher prevalence of anxiety and depression (25.0% vs. 4.6%, p = 0.000), as well as significantly elevated C-reactive protein (42.3 mg/L vs. 20.3 mg/L, p = 0.014) and D-dimer (0.3 mg/L vs. 0.22 mg/L, p = 0.024). note: 'Found by winnow, kev and lev in p003, p019, p023. Claude judged: partial.' - paper: pmid38240001 cited: true text: full license: by verdict: partial section: Abstract > Results quote: Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. note: 'Found by winnow, kev and lev in p003. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - long_covid papers: 4 evidence: - paper: pmid39301475 cited: true text: full license: by verdict: supports section: Relationship to post-infectious syndromes including long COVID quote: In patients with LC and dysautonomia, there is often a hyperadrenergic state, which drives many of the pathophysiologic mechanisms of hyperadrenergic POTS (25). note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid40014480 cited: true text: full license: by verdict: partial section: Discussion > Autonomic Dysfunction and COVID‐19 quote: The potential mechanisms are likely related to an imbalance between sympathetic and parasympathetic activity, as well as hemodynamic abnormalities such as reduced systemic venous return, augmented splanchnic and extremity pooling, decreased cardiac output, and decreased cerebral perfusion. This dysregulation manifests as a decrease in parasympathetic tone and an increase in sympathetic activity, particularly during postural changes from supine to upright positions. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid39076856 cited: true text: full license: by verdict: partial section: 5. Symptoms and Pathologic Findings of Cardiovascular Disease in Post-Acute COVID-19 Syndrome > 5.2 Pathologic Findings > 5.2.4 Postural Orthostatic Tachycardia Syndrome (POTS) quote: "Autonomic dysfunction in long COVID is provoked by the hyperadrenergic \nstate and the resetting of\ \ baroreceptor control, which is stimulated by \nangiotensin II upregulation." note: 'Found by winnow, kev and lev in p043, p042. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: Although the exact pathophysiology mechanism is unclear, it is thought that the combination of autoimmunity, relative central hypovolemia, small fiber neuropathy, hyperadrenergic stimulation, and pro-inflammatory cytokine production (i.e., cytokine storm) is a critical factor in POTS and COVID-19 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - edge: - long_covid - associated_with - mast_cell_activation papers: 4 evidence: - paper: pmid37255928 cited: true text: full license: by verdict: partial section: Associations with mast cell activation disorders quote: A prominent overlapping symptom cluster associated with both POTS [56, 57] and Long Covid [89, 90] includes a multi-system and often non-specific symptom cluster which is often referred to as ‘mast cell activation syndrome’ (and considered to be due to release of mast cell mediators) and includes gastrointestinal disturbances (nausea, vomiting, diarrhoea, cramps), asthma like symptoms, flushing, urticaria, angioedema and constitutional symptoms such as fatigue and fever [91]. note: 'Found by winnow, kev and lev in p026, p028. Claude judged: partial.' - paper: pmid36981522 cited: true text: full license: by verdict: partial section: 5. Discussion quote: Afrin and colleagues have hypothesized that pre-existing MCAS might predispose patients to develop long-COVID after a SARS-CoV-2 infection by contributing to a hyperinflammatory response [35]. Our patient had not been diagnosed with MCAS prior to the acute infection but had a strong history of allergies, and his plasma histamine levels were elevated on several occasions, consistent with that diagnosis. note: 'Found by winnow, kev and lev in p023, p025, p034. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 5. How Does SARS-CoV-2 Infection Cause Long-Term Dysautonomia? quote: A case of mast cell activation syndrome was described in a 50-year-old female with previous COVID-19 with signs and symptoms of POTS [52]. note: 'Found by winnow, kev and lev in p028, p038. Claude judged: partial.' - paper: pmid33869099 cited: true text: abstract license: none verdict: partial section: Abstract > Learning Points quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33869099. Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - neuropathic_evidence papers: 4 evidence: - paper: pmid38537312 cited: true text: abstract license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38537312. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid41089328 cited: true text: full license: by verdict: partial section: Autoimmunity > Association with autonomic neuropathy quote: However, a non-length-dependent or patchy distribution of small fiber neuropathy can also occur, especially in conjunction with systemic autoimmune disorders (Gemignani et al., 2022). Autoimmune and immune-mediated etiologies have been suggested as among the major underlying mechanisms in autonomic neuropathy, with immunotherapy being recommended as the first-line treatment (Gavrilova et al., 2022; Maier et al., 2022; Gendre, 2024; Nakane et al., 2024). note: 'Found by winnow, kev and lev in p018, p001, p022. Claude judged: partial.' - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: In this cohort, there was a trend toward higher rates of comorbid autoimmune disease among patients with evidence of SFN compared to patients without, though the difference was not statistically significant. Patients with systemic autoimmune diseases may be at slightly increased risk for developing a neuropathic POTS phenotype - for instance, Sjogren’s syndrome is diagnosed at higher rates among POTS patients who have reduced IENFD [26]. note: 'Found by winnow, kev and lev in p037, p039. Claude judged: partial.' - paper: pmid28116654 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 28116654. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - gi_dysmotility - associated_with - neuropathic_evidence papers: 4 evidence: - paper: pmid42153984 cited: true text: full license: by verdict: supports section: Discussion > Comorbidities quote: An association between neuropathy and gastrointestinal and bladder symptoms bas been recognized in patients with POTS [25]. note: 'Found by winnow, kev and lev in p048. Claude judged: supports.' - paper: pmid29549458 cited: true text: full license: none verdict: supports section: Results > Postural Tachycardia Syndrome and Gastrointestinal Symptoms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29549458. Found by winnow, kev and lev in p011, p014, p024. Claude judged: supports.' - paper: pmid23708963 cited: true text: full license: none verdict: supports section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23708963. Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid41858767 cited: true text: full license: by-nc-nd verdict: partial section: Abstract quote: Bowel and skin biopsies from patients with gastrointestinal disorders have revealed neuropathic changes and altered connective tissue. note: 'Found by winnow, kev and lev in p004, p001. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - post_vaccination_onset papers: 4 evidence: - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 1. Introduction quote: The diagnosis of orthostatic intolerance is often preceded by a viral illness or vaccination [12,13,14,15,16]. In the COVID-19 era, orthostatic intolerance was frequently encountered post SARS-CoV-2 infection and vaccination, providing further evidence of an autoimmune etiology [16,17]. note: 'Found by winnow, kev and lev in p006, p034. Claude judged: supports.' - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: Several clinical observations suggest that autoimmune pathophysiology plays a role in POTS. These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid36475233 cited: true text: full license: by verdict: partial section: Discussion quote: Although the exact mechanism of vaccine-induced POTS is not clear, the autoimmune pathophysiology might be a key component [13-15]. note: 'Found by winnow, kev and lev in p014, p004. Claude judged: partial.' - paper: pmid35870086 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p012, p005, p006. Claude judged: partial.' - edge: - me_cfs - associated_with - postinfectious_evidence papers: 4 evidence: - paper: pmid36639608 cited: true text: full license: none verdict: supports section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p021, p022. Claude judged: supports.' - paper: pmid38600563 cited: true text: full license: by verdict: partial section: Background quote: Following acute SARS-CoV-2 infection, a subset of individuals continues to suffer from lingering symptoms very similar to those associated with ME/CFS. It has been estimated that about half of people presenting with long COVID at six months meet the case criteria for ME/CFS [7, 8]. note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - paper: pmid33996867 cited: true text: full license: by verdict: partial section: Introduction quote: We recently evaluated three adolescents and young adults in whom COVID-19 illness had been confirmed with direct testing or was highly suspected based on the timing of the onset of symptoms in association with peak local and regional pandemic cases, close exposure to confirmed cases, along with characteristic clinical features such as anosmia. In all three, ME/CFS symptoms were prominent from the outset, as were symptoms and signs of orthostatic intolerance, consistent with an early contribution of circulatory disturbances to the pathogenesis of symptoms, before the onset of physiological changes due to inactivity. note: 'Found by winnow, kev and lev in p004, p006, p013. Claude judged: partial.' - paper: pmid29391028 cited: true text: full license: by verdict: partial section: Results > Case reports quote: Patient 1 was well until a viral gastrointestinal illness at age 12. Thereafter she reported progressive fatigue along with unrefreshing sleep, post-exertional malaise (PEM), problems with short-term memory and attention, headache, myalgias, arthralgias, sore throat, and tender glands, thus satisfying the clinical criteria for ME/CFS. note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - edge: - endometriosis - associated_with - pots papers: 4 evidence: - paper: pmid42787977 cited: true text: full license: by verdict: supports section: Abstract quote: Among 1,322 female POTS patients, 229 (17.3%) also carried a diagnosis of endometriosis. note: 'Found by winnow, kev and lev in p003, p004, p007. Claude judged: supports.' - paper: pmid42641290 cited: true text: abstract license: none verdict: supports section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42641290. Found by winnow, kev and lev in p003, p004. Claude judged: supports.' - paper: pmid37234076 cited: true text: full license: by verdict: supports section: 'Female reproductive health in illnesses comorbid or associated with Long COVID: A brief overview of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS), and endometriosis > Endometriosis' quote: Approximately 36% of women with ME/CFS (n = 36) and 20% of women with POTS (n = 65) report endometriosis (42, 48, 88). note: 'Found by winnow, kev and lev in p020, p026. Claude judged: supports.' - paper: pmid22721633 cited: true text: full license: none verdict: supports section: 4. Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 22721633. Found by winnow, kev and lev in p019, p024. Claude judged: supports.' - edge: - iron_deficiency - associated_with - pots papers: 4 evidence: - paper: pmid32974246 cited: true text: full license: by verdict: supports section: Perspectives on the Pathogenesis of Pots > Iron Insufficiency quote: Low ferritin and vitamin D levels have been found in adolescents with POTS (78). Low iron storage accompanied by mild anemia is more prevalent in pediatric POTS patients than in healthy children in the United States (79). note: 'Found by winnow, kev and lev in p017, p024. Claude judged: supports.' - paper: pmid23720007 cited: true text: abstract license: none verdict: supports section: Abstract > Interpretation quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23720007. Found by winnow, kev and lev in p003, p004, p001. Claude judged: supports.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Additional Associations and Postural Orthostatic Tachycardia Syndrome Mimickers > Iron Deficiency and Anemia quote: Whether iron deficiency is specifically related to POTS or serves as a mimicker via diminished venous return is still under review.[11] note: 'Found by winnow, kev and lev in p038. Claude judged: partial.' - paper: pmid21886073 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21886073. Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - sleep_disturbance papers: 4 evidence: - paper: pmid42254140 cited: true text: full license: by verdict: supports section: Body quote: Evidence suggests that during sleep, POTS patients can enter a hyperadrenergic state, disrupting normal autonomic regulation and perpetuating a vicious cycle of poor sleep and worsened daytime symptoms[4]. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid35303039 cited: true text: full license: by verdict: partial section: Introduction quote: Compared with a control group, the nocturnal catecholamine levels were increased in patients with insomnia [12]. note: 'Found by winnow, kev and lev in p024, p006. Claude judged: partial.' - paper: pmid25474569 cited: true text: full license: by verdict: partial section: Discussion quote: Lastly, the possible explanation was that the sleep disturbance might relate with heightened sympathetic activation [36]. note: 'Found by winnow, kev and lev in p028. Claude judged: partial.' - paper: pmid23538032 cited: true text: full license: none verdict: partial section: DISCUSSION > Possible Mechanisms of Poor Sleep Quality quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23538032. Found by winnow, kev and lev in p039, p041, p004. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - hyperadrenergic_evidence papers: 3 evidence: - paper: pmid40537187 cited: true text: full license: by-nc-nd verdict: supports section: Results > AR autoantibody activity in patients with POTS quote: Previous studies have shown that patients with hyperadrenergic POTS exhibit increased AR autoantibodies activity, characterized by enhanced β1-AR and diminished α1-AR signaling.28 note: 'Found by winnow, kev and lev in p025, p044, p004. Claude judged: supports.' - paper: pmid33886735 cited: true text: full license: by verdict: partial section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Nos casos de pacientes com SPOT que apresentam a síndrome de ativação dos mastócitos, um fator autoimune pode estar presente. Esses pacientes apresentam rubor da pele e hipertensão associada com a taquicardia ortostática. note: 'Found by winnow, kev and lev in p124. Claude judged: partial.' - paper: pmid29682372 cited: true text: full license: by verdict: partial section: 3. Discussion quote: This study entails specific antibodies, such as ganglionic acetylcholine receptor antibody [8] and alpha-1 adrenergic receptor antibody that act as partial antagonists and induce reflex compensatory sympathetic activation [9]. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - edge: - fibromyalgia - associated_with - hypermobility_heds papers: 3 evidence: - paper: pmid25917768 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25917768. Found by winnow, kev and lev in p014, p003, p015. Claude judged: supports.' - paper: pmid42691689 cited: true text: full license: none verdict: partial section: Autonomic system degenerations, generalized dysautonomia, and disorders of autonomic dysregulation > Postural orthostatic tachycardia syndrome quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42691689. Found by winnow, kev and lev in p044. Claude judged: partial.' - paper: pmid39582682 cited: true text: full license: by verdict: partial section: Headache disorders in hEDS and HSD > Migraine quote: In patients who had both HSD/hEDS and fibromyalgia, migraine was reported in 63.8% and chronic migraine in 34.1% (18). note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - me_cfs papers: 3 evidence: - paper: pmid41282714 cited: true text: full license: by verdict: supports section: Conclusions quote: Patients with hEDS demonstrated significantly elevated rates of comorbid conditions, particularly MCAS, POTS, and ME/CFS, which were also associated with increased likelihood of developing Long COVID. note: 'Found by winnow, kev and lev in p006, p011, p049. Claude judged: supports.' - paper: pmid40978926 cited: true text: full license: by verdict: supports section: Discussion quote: Third, JH and hEDS are risk factors for ME/CFS, and there is emerging evidence that hEDS is also a risk factor for TOS. note: 'Found by winnow, kev and lev in p030, p033. Claude judged: supports.' - paper: pmid24934205 cited: true text: full license: by-nc verdict: partial section: Discussion quote: Our finding of high levels of comorbidity, particularly CFS and EDS, is important as it might point towards an underlying overlapping mechanism.23–25 We believe that more work is needed to understand this spectrum of diseases and whether lessons could be learnt from one disease that could be applied to others. note: 'Found by winnow, kev and lev in p033. Claude judged: partial.' - edge: - functional_neurological_disorder - associated_with - pots papers: 3 evidence: - paper: pmid38953100 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: These concurrent symptoms lead patients to accumulate multiple comorbid disorders, including fibromyalgia, chronic fatigue syndrome, and postural orthostatic tachycardia syndrome. note: 'Found by winnow, kev and lev in p003, p025. Claude judged: supports.' - paper: pmid42804409 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 42804409. Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid37378164 cited: true text: full license: by verdict: partial section: Case presentation quote: A diagnosis of conversion disorder was presumed due to the rare seizure-like activity in POTS. note: 'Found by winnow, kev and lev in p006, p009. Claude judged: partial.' - edge: - hormonal_transition_onset - associated_with - pots papers: 3 evidence: - paper: pmid41753164 cited: true text: full license: by verdict: supports section: Abstract quote: Hormonal influence has been long recognized by the disorder predominantly affecting women of reproductive age, with frequent onset around menarche, exacerbation of symptoms before or during menses, and pregnancy being one of POTS triggers. note: 'Found by winnow, kev and lev in p001, p018. Claude judged: supports.' - paper: pmid36908200 cited: true text: full license: none verdict: partial section: 'Results: > Initial POTS onset during pregnancy:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36908200. Found by winnow, kev and lev in p032, p030. Claude judged: partial.' - paper: pmid31798399 cited: true text: full license: by verdict: partial section: Pubertal Hormones as Potential Contributors to Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: While it is certainly not possible to imply causality between these pubertal hormone changes and disorders of orthostatic tolerance in adolescents, the coincidental timing of these profound hormonal changes – many of which have marked cardiovascular effects - and the timing of onset of VVS and POTS, together with the observation that many youth “grow out” of their symptoms (Kizilbash et al., 2014), is suggestive of a link between pubertal hormone changes and susceptibility to syncope in females. note: 'Found by winnow, kev and lev in p005, p054, p001. Claude judged: partial.' - edge: - anxiety_depression - associated_with - gi_dysmotility papers: 2 evidence: - paper: pmid39543811 cited: true text: full license: by verdict: supports section: Abstract > Key Results quote: In cluster 0, we demonstrated increased somatization (p <0.0001), anxiety (p <0.0001), depression (p <0.0001), PoTS prevalence (p = 0.003), autonomic symptoms (p <0.0001) and reduced quality of life (p <0.0001) compared to cluster 2. note: 'Found by winnow, kev and lev in p003, p005, p050. Claude judged: supports.' - paper: pmid41952073 cited: true text: full license: by verdict: partial section: Discussion quote: Extra‐intestinal comorbidities, including anxiety, chronic fatigue, migraines, and depression, were reported in over one‐third of POTS patients, occurring more frequently than gastrointestinal conditions. IBS is the most common DGBI affecting 25% of POTS patients. note: 'Found by winnow, kev and lev in p005, p032. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - gi_dysmotility papers: 2 evidence: - paper: pmid34993884 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34993884. Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid33621398 cited: true text: full license: by verdict: supports section: Discussion quote: In this study, we confirmed that GI symptom onset, POTS, dry eye only, and nausea and vomiting among upper GI dysfunctions were frequent in pediatric patients with AAD. note: 'Found by winnow, kev and lev in p024. Claude judged: supports.' - edge: - anxiety_depression - associated_with - hyperadrenergic_evidence papers: 2 evidence: - paper: pmid23580201 cited: true text: full license: by verdict: supports section: DISCUSSION quote: Activation of the SNS has been associated with depression and patients with major depression are at an increased risk for heart disease (Musselman et al., 1998). Interestingly, a cardiac NE uptake deficiency, characterized by decreased clearance of NE in the heart, and decreased DHPG:NE ratios, like that seen in POTS, has been described in individuals with depression (Barton et al., 2007). note: 'Found by winnow, kev and lev in p003, p018. Claude judged: supports.' - paper: pmid40276022 cited: true text: full license: by-nc-nd verdict: partial section: Discussion quote: What’s more, researchres confirmed that anxiety and depression could act on hypothalamic-pituitary-adrenocortical axis (HPA) and produce hyperactivity of the sympathetic nervous system (Remme, 1998). Studies have shown that depression and anxiety could increase sympathetic excitability, upregulated levels of catecholamine in the blood, and heart rate (Wang et al., 2018). note: 'Found by winnow, kev and lev in p007, p020. Claude judged: partial.' - edge: - anxiety_depression - associated_with - hypermobility_heds papers: 2 evidence: - paper: pmid41446482 cited: true text: full license: by verdict: partial section: Discussion quote: A small category of POTS patients with co-existing Ehlers-Danlos syndrome type III (hypermobility type) also present with a spectrum of psychiatric illnesses comprising anxiety disorders, particularly panic disorders and agoraphobia [20]. note: 'Found by winnow, kev and lev in p086, p003. Claude judged: partial.' - paper: pmid32295399 cited: true text: full license: by verdict: partial section: Case quote: She had developed anxiety and depression secondary to the highly disabling headache. She had recently been diagnosed with hypermobile Ehlers Danlos Syndrome (hEDS). note: 'Found by winnow, kev and lev in p006. Claude judged: partial.' - edge: - arrhythmia_differential - associated_with - long_covid papers: 2 evidence: - paper: pmid40692561 cited: true text: full license: by verdict: partial section: Methods and analysis > Design, selection/treatment of subjects, interventional methods, data analysis > Aims and objectives quote: The second aim is to determine the potential benefits of ivabradine treatment for those with LHC-associated POTS or IST. note: 'Found by winnow, kev and lev in p005, p001, p020. Claude judged: partial.' - paper: pmid35355961 cited: true text: full license: by verdict: partial section: “Post-COVID-19 Tachycardia Syndrome” quote: It has been suggested that persistent tachycardia seen in long COVID, labelled “post-COVID-19 tachycardia syndrome,” may present as inappropriate sinus tachycardia or POTS (22). note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - associated_with - long_covid papers: 2 evidence: - paper: pmid40014480 cited: true text: full license: by verdict: partial section: Discussion > Autonomic Dysfunction and COVID‐19 quote: The potential mechanisms are likely related to an imbalance between sympathetic and parasympathetic activity, as well as hemodynamic abnormalities such as reduced systemic venous return, augmented splanchnic and extremity pooling, decreased cardiac output, and decreased cerebral perfusion. note: 'Found by winnow, kev and lev in p023. Claude judged: partial.' - paper: pmid39875497 cited: true text: full license: by verdict: partial section: Discussion quote: Interestingly, others have used various imaging techniques to evaluate neurocognitive dysfunction including F-Fluorodeoxyglucose positron emission tomography (F-FDG-PET), functional MRI, diffusion MRI, and SPECT in those with PASC27. They identified a high prevalence of functional imaging abnormalities in PASC with findings of cerebral hypoperfusion that correlated with functional decline27. note: 'Found by winnow, kev and lev in p011, p006, p015. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - long_covid papers: 2 evidence: - paper: pmid41282714 cited: true text: full license: by verdict: supports section: Abstract quote: Patients with hEDS were more likely to be diagnosed with Long COVID compared to similar patients without hEDS. This was especially true for those who also had conditions such as chronic fatigue, immune conditions, or issues with heart rate and blood pressure regulation. note: 'Found by winnow, kev and lev in p006, p011, p045. Claude judged: supports.' - paper: pmid40624434 cited: true text: full license: by verdict: supports section: Clinical features and evaluation of dysautonomia quote: Assessment for joint hypermobility with the Beighton scale is warranted in patients with dysautonomia to identify hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (EDS), which are highly prevalent in patients with POTS, post-COVID dysautonomia and other forms of dysautonomia [22]. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - edge: - hypovolemic_evidence - associated_with - long_covid papers: 2 evidence: - paper: pmid38240001 cited: true text: full license: by verdict: partial section: INTRODUCTION quote: Factors contributing to the development of POTS after COVID‐19 infection are hypovolemia, neurotropism, inflammation, and autoimmunity. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid37435242 cited: true text: full license: by verdict: partial section: Discussion quote: In the majority of patients, intravascular volume is reduced, thus leading to decreased venous return to the heart and causing reflex tachycardia and orthostatic intolerance. Patients who have been on prolonged bed rest or are in a deconditioned state are likely to develop decreased blood volume [5]. note: 'Found by winnow, kev and lev in p001, p004, p005. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - mast_cell_activation papers: 2 evidence: - paper: pmid35062788 cited: true text: full license: by verdict: partial section: 6. Discussion quote: Another hypothesized mechanism, seemingly congruent with an observed non-trivial frequency with which MCAS and some associated comorbidities seem to drive the humoral immune system to erroneously produce unneeded antibodies [66,69,70,71,72,73,74,75,76], might be MCAS-induced production of autoantibodies driving vasodilation via direct or indirect action upon the vascular endothelium. note: 'Found by winnow, kev and lev in p020, p021. Claude judged: partial.' - paper: pmid33886735 cited: true text: full license: by verdict: partial section: Síndrome Postural Ortostática Taquicardizante (SPOT) quote: Nos casos de pacientes com SPOT que apresentam a síndrome de ativação dos mastócitos, um fator autoimune pode estar presente. note: 'Found by winnow, kev and lev in p124. Claude judged: partial.' - edge: - gi_dysmotility - associated_with - mast_cell_activation papers: 2 evidence: - paper: pmid40856938 cited: true text: full license: by verdict: partial section: Discussion quote: Mast cell activation syndrome (MCAS) is also a common comorbid condition in POTS, which induces abdominal cramping and bloating associated with enhanced secretion of histamine and inflammatory cytokines [1, 17]. note: 'Found by winnow, kev and lev in p014. Claude judged: partial.' - paper: pmid29326369 cited: true text: full license: by-nc verdict: partial section: Background quote: Gastrointestinal (GI) symptoms are common in both syndromes.1–4 6 GI symptoms in MCAS can be explained by inappropriate release of mediators from mast cells (MCs) with KIT mutations whereas GI motility disorders in POTS may be due to active autoimmune muscarinic antibodies causing autonomic imbalance in some patients (S Vernino, personal communication, 2017).2 note: 'Found by winnow, kev and lev in p002, p016, p019. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - neuropathic_evidence papers: 2 evidence: - paper: pmid40843452 cited: true text: full license: by-nc-nd verdict: supports section: Abstract > Conclusions quote: This study provided evidence of cerebrovascular dysregulation with reduced orthostatic cerebral blood flow velocity associated with symptoms of cerebral hypoperfusion, frequent small fiber neuropathy, and widespread but mild autonomic failure in hEDS. note: 'Found by winnow, kev and lev in p005, p047. Claude judged: supports.' - paper: pmid34055418 cited: true text: full license: by verdict: partial section: 3. Discussion quote: The association between POTS and JHS can be explained by predominant peripheral neuropathy in the autonomous system and a failure of the peripheral vascular system to maintain resistance in areas exposed to stress due to orthostasis, blood stasis in the lower limbs, or pathologies of the central nervous system [11]. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - edge: - mast_cell_activation - associated_with - post_vaccination_onset papers: 2 evidence: - paper: pmid40729147 cited: true text: full license: by verdict: partial section: 3. Discussion quote: There is evidence that HPV vaccinations can trigger mast cell activation syndromes [15]. This can explain the association of HPV-triggered POTS and the association of EDS type III. note: 'Found by winnow, kev and lev in p011. Claude judged: partial.' - paper: pmid35062788 cited: true text: full license: by verdict: partial section: Abstract quote: We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. note: 'Found by winnow, kev and lev in p001, p007, p023. Claude judged: partial.' - edge: - anxiety_depression - associated_with - postinfectious_evidence papers: 2 evidence: - paper: pmid38510743 cited: true text: full license: by-nc-nd verdict: partial section: Long Covid syndrome, neuro-cardiologic complications and prognosis quote: A long Covid syndrome may be clinically manifested with orthostatic hypotension, postural orthostatic tachycardia syndrome (POTS), syncope, chest pain, dyspnea, palpitation, chronic fatigue syndrome, ‘brain fog’, memory, cognitive and sleep difficulties, anosmia, headache, signs of impaired cardiac and cerebral perfusion, depression and anxiety [57,59,60]. A higher prevalence of psychiatric syndromes - post-traumatic stress disorder (PTSD) (28 %), depression (31 %), anxiety (42 %), insomnia (40 %), and obsessive-compulsive (OS) symptoms (20 %) was also reported [61]. note: 'Found by winnow, kev and lev in p001, p026, p028. Claude judged: partial.' - paper: pmid34821709 cited: true text: full license: by verdict: partial section: 3. COVID-19 Infection and Dysautonomia quote: Recent evidence showed the significant burden of fatigue, symptoms of autonomic dysfunction, and mood disorders in the aftermath of COVID-19 infection, but reassuringly did not demonstrate pathological findings during investigations for autonomic function [33]. Fatigue is linked to the higher prevalence of anxiety and post-traumatic stress disorder in COVID-19 survivors [23,27,33,54], while somatic anxiety in patients with chronic fatigue has been directly associated with autonomic nervous system dysfunction [55]. note: 'Found by winnow, kev and lev in p013. Claude judged: partial.' - edge: - mast_cell_activation - associated_with - postinfectious_evidence papers: 2 evidence: - paper: pmid41282714 cited: true text: full license: by verdict: partial section: Discussion quote: Comorbid conditions commonly observed in hEDS, including MCAS, POTS, and ME/CFS, were significantly more prevalent in patients with hEDS with Long COVID than in those without. note: 'Found by winnow, kev and lev in p046, p045. Claude judged: partial.' - paper: pmid33869099 cited: true text: abstract license: none verdict: partial section: Abstract > Learning Points quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33869099. Found by winnow, kev and lev in p001, p002. Claude judged: partial.' - edge: - neuropathic_evidence - associated_with - postinfectious_evidence papers: 2 evidence: - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: INTRODUCTION quote: Because viral infection can host various chronic neurological conditions, such as Guillain-Barre syndrome, POTS can possibly occur as a post-COVID-19 autonomic nerve involvement. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - paper: pmid36639608 cited: true text: full license: none verdict: partial section: Major findings > ME/CFS, dysautonomia and related conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36639608. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - post_vaccination_onset - associated_with - postinfectious_evidence papers: 2 evidence: - paper: pmid38173801 cited: true text: full license: by-nc verdict: partial section: POTS and Functional Autoantibodies quote: These observations include disease onset following viral infections or vaccination, family history of systemic autoimmune disorders, and association with peripheral neuropathy of autoimmune origin.[2] note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports quote: Contemporary literature indicates potential links between viral infections and vaccines (particularly HPV) with the development of POTS.14,35,36 note: 'Found by winnow, kev and lev in p021. Claude judged: partial.' - edge: - arrhythmia_differential - associated_with - pots papers: 2 evidence: - paper: pmid33654569 cited: true text: full license: by verdict: supports section: Introduction quote: Moreover, the presence of coexisting arrhythmia can make symptoms difficult to control. Assessing and treating POTS patients for underlying SVT can improve their POTS symptoms and, thus, their quality of life.7 The purpose of this study was to bring forth the observation that SVT and POTS can occur together. note: 'Found by winnow, kev and lev in p002, p001, p007. Claude judged: supports.' - paper: pmid34035985 cited: true text: full license: by verdict: partial section: Abstract quote: Here, we present one of the first case series demonstrating a similar relationship between sinus node dysfunction and much rarer etiologies of tachyarrhythmia—that is, postural tachycardia syndrome and inappropriate sinus tachycardia. note: 'Found by winnow, kev and lev in p001, p016. Claude judged: partial.' - edge: - surgery_onset - associated_with - pots papers: 2 evidence: - paper: pmid41561794 cited: true text: full license: by verdict: partial section: Abstract quote: A 39-year-old woman developed debilitating systemic symptoms following the placement of a synthetic mid-urethral sling for stress urinary incontinence. Previously in good health, she experienced sepsis and adrenal crisis immediately postoperatively, followed by persistent symptoms including fatigue, postural orthostatic tachycardia syndrome (POTS), neuropathic pain, cognitive dysfunction, autonomic instability, and recurrent infections. note: 'Found by winnow, kev and lev in p001, p015. Claude judged: partial.' - paper: pmid22889291 cited: true text: full license: by verdict: partial section: Abstract > Introduction quote: We report a case of postural tachycardia syndrome occurring after the surgical correction of an aortic coarctation, and coexisting with upper airway resistance syndrome. note: 'Found by winnow, kev and lev in p004, p001, p003. Claude judged: partial.' - edge: - deconditioning_evidence - associated_with - prolonged_bed_rest papers: 2 evidence: - paper: pmid34265539 cited: true text: full license: none verdict: partial section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p030. Claude judged: partial.' - paper: pmid29523389 cited: true text: full license: none verdict: partial section: 4. Pathophysiology of POTS > 4.8 Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - anxiety_depression - associated_with - sleep_disturbance papers: 2 evidence: - paper: pmid40648966 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Both patients with MDD and anxiety presented at older age, were less sleepy, and reported more frequently disrupted sleep than their non-affected counterparts. note: 'Found by winnow, kev and lev in p016, p019, p020. Claude judged: partial.' - paper: pmid28442939 cited: true text: full license: by-nc verdict: partial section: Introduction quote: Insomnia has been linked with increased rates of depression,19 and approximately 50% of people with invisible illness suffer from depression,20 one of the greatest risk factors for suicide. note: 'Found by winnow, kev and lev in p004, p007. Claude judged: partial.' - edge: - neuropathic_evidence - associated_with - systemic_autoimmune_disease papers: 2 evidence: - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: Patients with systemic autoimmune diseases may be at slightly increased risk for developing a neuropathic POTS phenotype - for instance, Sjogren’s syndrome is diagnosed at higher rates among POTS patients who have reduced IENFD [26]. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: Postural orthostatic tachycardia syndrome has also been reported in association with Sjögren's syndrome and celiac disease, both of which are known to cause autonomic neuropathies.73,74 note: 'Found by winnow, kev and lev in p031. Claude judged: partial.' - edge: - anxiety_depression - associated_with - cerebral_hypoperfusion_evidence papers: 1 evidence: - paper: pmid30883381 cited: true text: full license: by-nc verdict: partial section: Comments > Differential diagnosis of hemodynamic orthostatic dizziness/vertigo quote: However, a positive screen for anxiety or depression does not rule out a hemodynamic or other causes of symptoms as psychiatric disorders often co-exist with medical morbidity. note: 'Found by winnow, kev and lev in p038. Claude judged: partial.' - edge: - anxiety_depression - associated_with - endometriosis papers: 1 evidence: - paper: pmid42787977 cited: true text: full license: by verdict: supports section: Introduction quote: Much like POTS, endometriosis exerts a substantial toll on both quality of life and psychological well-being. Affected individuals frequently experience anxiety, depression, fatigue, and limitations in social and occupational activities [9,10]. note: 'Found by winnow, kev and lev in p030, p004, p006. Claude judged: supports.' - edge: - cerebral_hypoperfusion_evidence - associated_with - fibromyalgia papers: 1 evidence: - paper: pmid41602336 cited: true text: full license: by verdict: supports section: Discussion quote: Patients with chronic fatigue, POTS, and fibromyalgia experience decreased blood flow to the brain (9, 11, 17, 18) and therefore vascularly linked. note: 'Found by winnow, kev and lev in p025. Claude judged: supports.' - edge: - chronic_migraine - associated_with - fibromyalgia papers: 1 evidence: - paper: pmid23862007 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: Fibromyalgia was diagnosed in between 22 and 40% of migraine [8]. Patients who suffered from both migraine and fibromyalgia were older, and reported incapacitating headaches, more insomnia and mental stress, and lower quality of life [8]. note: 'Found by winnow, kev and lev in p001, p010, p002. Claude judged: supports.' - edge: - deconditioning_evidence - associated_with - fibromyalgia papers: 1 evidence: - paper: pmid23862007 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: Deconditioning of the muscles, consequence of pain related physical inactivity, is assumed to lead to autonomic dysfunction in fibromyalgia [3]. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - edge: - anxiety_depression - associated_with - functional_neurological_disorder papers: 1 evidence: - paper: pmid38953100 cited: true text: full license: by-nc-nd verdict: partial section: FND and comorbid conditions and the autonomic nervous system > Autonomic nervous system in psychiatric symptoms and disorders quote: Psychiatric symptoms and disorders are often co-occurrent with FND and considered risk factors [118]. Psychiatric disorders have characteristic autonomic patterns. note: 'Found by winnow, kev and lev in p009, p042. Claude judged: partial.' - edge: - deconditioning_evidence - associated_with - gi_dysmotility papers: 1 evidence: - paper: pmid25483980 cited: true text: full license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p027, p003, p022. Claude judged: supports.' - edge: - fibromyalgia - associated_with - gi_dysmotility papers: 1 evidence: - paper: pmid39543811 cited: true text: full license: by verdict: partial section: RESULTS > Downstream statistical analysis > Somatization—PHQ‐12 scores (Tables 5 and 6) quote: Patients with overlap hEDS/HSD + IBS had significantly higher median PHQ‐12 scores than hEDS/HSD alone (p <0.01). This cluster had significantly more fibromyalgia pain type symptoms such as back pain, pains in the arms/legs/joints and headaches versus hEDS/HSD alone (p ≤ 0.05) (D1 and D2). note: 'Found by winnow, kev and lev in p032. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - associated_with - hormonal_transition_onset papers: 1 evidence: - paper: pmid31798399 cited: true text: full license: by verdict: partial section: Pubertal Hormones as Potential Contributors to Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: It is conceivable that pubertal increases in these hormones, many of which have secondary actions to promote vasodilatation, impair vasoconstriction, decrease blood volume, promote hypocapnia and cerebral hypoperfusion, and contribute to excessive tachycardia, unmask a susceptibility to disorders of orthostatic intolerance in girls with a previously unknown predisposition to poor orthostatic tolerance. note: 'Found by winnow, kev and lev in p054. Claude judged: partial.' - edge: - chronic_migraine - associated_with - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid38912309 cited: true text: full license: by verdict: partial section: Theoretical and auto/biographical review > Recovery and expectations quote: '‘A frequently described comorbidity in POTS patients is migraine, as well as other chronic headache types’ (Bryarly et al., 2019: 1216); ‘Intractable migraines often lead to physical inactivity, which may exacerbate orthostatic intolerance, and conversely, the increased sympathetic activity associated with POTS may contribute to increased frequency of headaches’ (Bryarly et al., 2019).' note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - edge: - deconditioning_evidence - associated_with - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid33860871 cited: true text: full license: none verdict: partial section: Results > Representative cases > Postural tachycardia syndrome > Patient 1 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33860871. Found by winnow, kev and lev in p026, p040, p041. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - associated_with - hypermobility_heds papers: 1 evidence: - paper: pmid39875497 cited: true text: full license: by verdict: supports section: Discussion quote: Others have shown that those with joint hypermobility and myalgic encephalomyelitis had more pronounced reduction in CBF on transcranial doppler during orthostatic stress than those without joint hypermobility28. In our study, hEDS was similarly associated with higher rates of abnormal CBF on SPECT, highlighting the need for further investigations into the interrelated effects of these disorders and neurocognitive impairment. note: 'Found by winnow, kev and lev in p012, p006, p015. Claude judged: supports.' - edge: - deconditioning_evidence - associated_with - hypermobility_heds papers: 1 evidence: - paper: pmid34331416 cited: true text: full license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34331416. Found by winnow, kev and lev in p001, p013. Claude judged: supports.' - edge: - cerebral_hypoperfusion_evidence - associated_with - hypovolemic_evidence papers: 1 evidence: - paper: pmid41602336 cited: true text: full license: by verdict: partial section: Discussion quote: Decreased cerebral blood flow has been correlated with brain fog symptoms, and what has been regarded as autonomic nervous system dysfunction could relate to functional hypovolemia because of venous pooling in the pelvis leading to decreased cardiac venous return and resulting diminished cerebral perfusion as described by Edgell et al. (15). note: 'Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - gi_dysmotility - associated_with - hypovolemic_evidence papers: 1 evidence: - paper: pmid25483980 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25483980. Found by winnow, kev and lev in p025. Claude judged: partial.' - edge: - hormonal_transition_onset - associated_with - hypovolemic_evidence papers: 1 evidence: - paper: pmid31798399 cited: true text: full license: by verdict: partial section: Pubertal Hormones as Potential Contributors to Vasovagal Syncope and Postural Orthostatic Tachycardia Syndrome quote: It is conceivable that pubertal increases in these hormones, many of which have secondary actions to promote vasodilatation, impair vasoconstriction, decrease blood volume, promote hypocapnia and cerebral hypoperfusion, and contribute to excessive tachycardia, unmask a susceptibility to disorders of orthostatic intolerance in girls with a previously unknown predisposition to poor orthostatic tolerance. note: 'Found by winnow, kev and lev in p054. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - hypovolemic_evidence papers: 1 evidence: - paper: pmid40601666 cited: true text: full license: by verdict: supports section: 1 Introduction quote: In addition, hypovolemia is closely associated with sympathetic nervous system (SNS) activation, which exacerbates the symptoms of tachycardia [9]. note: 'Found by winnow, kev and lev in p003. Claude judged: supports.' - edge: - deconditioning_evidence - associated_with - long_covid papers: 1 evidence: - paper: pmid34265539 cited: true text: full license: none verdict: partial section: Potential mechanisms of autonomic impairment in post-acute COVID syndrome > Deconditioning quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34265539. Found by winnow, kev and lev in p030. Claude judged: partial.' - edge: - anxiety_depression - associated_with - mast_cell_activation papers: 1 evidence: - paper: pmid38003876 cited: true text: full license: by verdict: supports section: Abstract quote: This syndrome is associated with various neurologic and psychiatric disorders, including headache, dysautonomia, depression, generalized anxiety disorder, and many others. note: 'Found by winnow, kev and lev in p001, p012, p016. Claude judged: supports.' - edge: - chronic_migraine - associated_with - mast_cell_activation papers: 1 evidence: - paper: pmid38003876 cited: true text: full license: by verdict: supports section: 5. Mast Cells quote: This MC-mediated pathway is thought to be one of the mechanisms underlying migraine pain pathophysiology, and migraine is one of the most common comorbidities noted in patients with MCAS [26]. note: 'Found by winnow, kev and lev in p018. Claude judged: supports.' - edge: - endometriosis - associated_with - mast_cell_activation papers: 1 evidence: - paper: pmid37241210 cited: true text: full license: by verdict: partial section: Abstract quote: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood. note: 'Found by winnow, kev and lev in p001, p003, p004. Claude judged: partial.' - edge: - cerebral_hypoperfusion_evidence - associated_with - me_cfs papers: 1 evidence: - paper: pmid32140630 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: The main finding of this study is that extracranial Doppler imaging demonstrates a significant reduction in cerebral blood flow during head-up tilt test in ME/CFS patients compared to healthy controls. note: 'Found by winnow, kev and lev in p073, p078, p084. Claude judged: supports.' - edge: - differential_syncope_oh - associated_with - me_cfs papers: 1 evidence: - paper: pmid35056406 cited: true text: full license: by verdict: partial section: 4. Discussion quote: Our study report on 429 ME/CFS patients shows that differences in hemodynamic outcomes as for instance hypotension or POTS can be present in ME/CFS patients with a high incidence of orthostatic intolerance [7]. note: 'Found by winnow, kev and lev in p001, p015, p018. Claude judged: partial.' - edge: - fibromyalgia - associated_with - me_cfs papers: 1 evidence: - paper: pmid40890788 cited: true text: full license: by verdict: supports section: Discussion quote: This hypothesis is supported by previous studies suggesting that sustained focus on changing bodily sensations enabled patients to effectively utilize mindfulness-related skills, re-establishing sensorimotor integration and facilitating non-judgmental reconnection with bodily sensations, which leads to improvements in physical and psychological symptoms, functionality, and quality of life for patients with fibromyalgia [24, 25], a common comorbidity of ME/CFS. note: 'Found by winnow, kev and lev in p015. Claude judged: supports.' - edge: - mast_cell_activation - associated_with - me_cfs papers: 1 evidence: - paper: pmid41300853 cited: true text: full license: by verdict: supports section: Abstract quote: 'Conclusions: MCA appears to be a frequent and clinically relevant comorbidity in ME/CFS and is associated with a higher prevalence of OI, particularly POTS.' note: 'Found by winnow, kev and lev in p001, p018, p020. Claude judged: supports.' - edge: - hypermobility_heds - associated_with - neurodevelopmental_disorder papers: 1 evidence: - paper: pmid41686757 cited: true text: abstract license: none verdict: supports section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 41686757. Found by winnow, kev and lev in p001. Claude judged: supports.' - edge: - hypovolemic_evidence - associated_with - neuropathic_evidence papers: 1 evidence: - paper: pmid33490373 cited: true text: full license: by verdict: partial section: Discussion quote: Patient's with postural tachycardia syndrome have peripheral autonomic dysfunction. A subset of patients with POTS has low levels of standing plasma renin activity, aldosterone, and blood volume as compared to normovolemic patients [10]. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - edge: - me_cfs - associated_with - neuropathic_evidence papers: 1 evidence: - paper: pmid37968647 cited: true text: full license: by verdict: partial section: Introduction quote: Both patients with post-COVID-19 condition and ME/CFS could develop these types of neuropathies [20–22]. note: 'Found by winnow, kev and lev in p009. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - physical_trauma_onset papers: 1 evidence: - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: partial section: COMORBIDITIES OF POTS AFFECTING EXERCISE TOLERANCE quote: The correlation between POTS and hereditary connective tissue disorders is particularly important in the postconcussion population as development of craniocervical instability, craniocervical dyskinesia, and Chiari brainstem compression requires critical medical attention and can be primarily related to concussion or whiplash injuries as well as hypermobile Ehlers-Danlos syndrome.71,72 note: 'Found by winnow, kev and lev in p030. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - post_vaccination_onset papers: 1 evidence: - paper: pmid40729147 cited: true text: full license: by verdict: partial section: 3. Discussion quote: Here, we recommend additional research and vigilance to identify potential associations with patients with hEDS developing POTS after HPV vaccination. note: 'Found by winnow, kev and lev in p017, p001, p006. Claude judged: partial.' - edge: - hyperadrenergic_evidence - associated_with - postinfectious_evidence papers: 1 evidence: - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: Although the exact pathophysiology mechanism is unclear, it is thought that the combination of autoimmunity, relative central hypovolemia, small fiber neuropathy, hyperadrenergic stimulation, and pro-inflammatory cytokine production (i.e., cytokine storm) is a critical factor in POTS and COVID-19 infection. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - edge: - hypermobility_heds - associated_with - postinfectious_evidence papers: 1 evidence: - paper: pmid41282714 cited: true text: full license: by verdict: partial section: Abstract quote: Patients with hEDS were more likely to be diagnosed with Long COVID compared to similar patients without hEDS. This was especially true for those who also had conditions such as chronic fatigue, immune conditions, or issues with heart rate and blood pressure regulation. note: 'Found by winnow, kev and lev in p006, p045, p046. Claude judged: partial.' - edge: - prolonged_bed_rest - associated_with - pots papers: 1 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: partial section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p059, p051. Claude judged: partial.' - edge: - secondary_sinus_tachycardia - associated_with - pots papers: 1 evidence: - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: It is still unclear if this is due to a high prevalence of anxiety as a coexisting condition in patients with POTS or if there is just an overlap of symptoms between the two conditions [49]. note: 'Found by winnow, kev and lev in p045, p049. Claude judged: partial.' - edge: - autoimmune_evidence - associated_with - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid38537312 cited: true text: abstract license: none verdict: partial section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38537312. Found by winnow, kev and lev in p003, p004. Claude judged: partial.' - edge: - long_covid - associated_with - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid39852767 cited: true text: full license: by verdict: partial section: 1. Introduction quote: Here, we present a case of a patient with IT and post-COVID POTS and SFN who experienced significant improvement of IT after receiving intravenous saline, suggesting that IT may be a symptom of POTS and SFN. note: 'Found by winnow, kev and lev in p005, p002, p003. Claude judged: partial.' - edge: - postinfectious_evidence - associated_with - small_fiber_neuropathy_dx papers: 1 evidence: - paper: pmid39852767 cited: true text: full license: by verdict: partial section: 2. Case Presentation quote: However, an autoimmune basis of post-COVID POTS was evident given a positive ANA, comorbid SFN, and post-infectious onset of symptomatology. note: 'Found by winnow, kev and lev in p005, p007. Claude judged: partial.' - edge: - sleep_disturbance - associated_with - surgery_onset papers: 1 evidence: - paper: pmid22889291 cited: true text: full license: by verdict: partial section: Introduction quote: To the best of our knowledge, this is the first reported case of POTS arising after this type of surgery. Additionally, a coexisting sleep-related breathing disorder characterized as upper airway resistance syndrome (UARS) was diagnosed by an extensive sleep study. note: 'Found by winnow, kev and lev in p004. Claude judged: partial.' - edge: - chronic_migraine - associated_with - systemic_autoimmune_disease papers: 1 evidence: - paper: pmid42299385 cited: true text: full license: by-nc-nd verdict: supports section: Discussion quote: Each of these manifestations has been described separately along with SS (8-10). In a study of 16 SS patients, 13 presented with a history of migraine (3). note: 'Found by winnow, kev and lev in p007, p003, p012. Claude judged: supports.' - edge: - small_fiber_neuropathy_dx - associated_with - systemic_autoimmune_disease papers: 1 evidence: - paper: pmid36349067 cited: true text: full license: by verdict: partial section: Discussion quote: In this cohort, there was a trend toward higher rates of comorbid autoimmune disease among patients with evidence of SFN compared to patients without, though the difference was not statistically significant. note: 'Found by winnow, kev and lev in p037. Claude judged: partial.' - edge: - postinfectious_evidence - trigger_of - pots papers: 30 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Discussion quote: Infectious illnesses are well-recognized POTS triggers, with up to 40% of COVID-unrelated POTS cases reporting a post-infectious symptom onset (e.g., following Epstein–Barr virus, Mycoplasma pneumoniae, influenza, or other upper respiratory infections) [20, 48]. note: 'Found by winnow, kev and lev in p003, p036, p041. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: supports section: 1. Introduction quote: POTS can be triggered by diverse initiating events, often making its exact initiating event challenging to pinpoint. Commonly, POTS is preceded by a viral infection, which can disrupt the autonomic nervous system’s functioning. note: 'Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid40533427 cited: true text: full license: by verdict: supports section: Body quote: Infection was the most frequent trigger of POTS symptom onset (197 people, 39.4%), including 163 with POTS secondary to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections (32.6%) (Box). note: 'Found by winnow, kev and lev in p003, p009. Claude judged: supports.' - paper: pmid39875497 cited: true text: full license: by verdict: supports section: Results > Participant characteristics quote: A discernible trigger with temporal proximity to POTS symptom onset was found in 71% of the cohort. SARS-CoV-2 infection was the most common of these (29%) followed by infections other than COVID-19 (20%), and trauma/concussion (13%). note: 'Found by winnow, kev and lev in p002, p005. Claude judged: supports.' - paper: pmid39838139 cited: true text: full license: by verdict: supports section: Discussion quote: Hence POTS, a syndrome most commonly triggered by viral infections, also associated with cognitive difficulties and highly prevalent among patients with LC, becomes a suitable option to achieve this objective. note: 'Found by winnow, kev and lev in p006, p044. Claude judged: supports.' - paper: pmid39678714 cited: true text: full license: by-nc verdict: supports section: Introduction quote: Researchers suggest that COVID-19 can trigger POTS, as a significant amount of patients who recover from COVID-19 are now showing POTS-like symptoms such as brain fog, tachycardia (elevated HR), and severe chronic fatigue.9 note: 'Found by winnow, kev and lev in p007, p008. Claude judged: supports.' - paper: pmid39552985 cited: true text: full license: by verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) often manifests following an acute infection. note: 'Found by winnow, kev and lev in p001, p005, p028. Claude judged: supports.' - paper: pmid38958137 cited: true text: full license: by-nc-nd verdict: supports section: RESULTS quote: The median age of onset of POTS symptoms was 13 (IQR 11–14) years, with over half of patients reporting onset within 3 months of a specific event (Table 3), such as infection (45.6%), concussion (22.8%), pubertal changes (7.0%), surgery (12.3%), growth spurt (6.1%), physical trauma/fracture (2.6%), or extreme stress or emotional trauma (1.8%) (Figure 4). note: 'Found by winnow, kev and lev in p024, p035. Claude judged: supports.' - paper: pmid38390594 cited: true text: full license: by verdict: supports section: Dysautonomia and small-fiber neuropathy often occur as a complication of certain infections quote: Approximately half of patients with POTS report symptoms of a preceding infection (3). Infectious causes of POTS include EBV, herpes viruses, flavivirus, enterovirus 71, retroviruses (HIV), and SARS-CoV-2 (7). note: 'Found by winnow, kev and lev in p002, p007. Claude judged: supports.' - paper: pmid37822957 cited: true text: full license: by verdict: supports section: Introduction quote: Up to 50% of patients with POTS describe a viral infection as the trigger of their symptoms. note: 'Found by winnow, kev and lev in p005, p006. Claude judged: supports.' - paper: pmid37391116 cited: true text: full license: none verdict: supports section: 'Discussion > Central Illustration > COVID-19: a Trigger for Dysautonomia?' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p025. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: Introduction > Clinical Features quote: Antecedent illness with viral infections of the upper respiratory and gastrointestinal tracts have been reported prior to onset of POTS.2,14,15 Offending organisms identified include Epstein-Barr virus, Influenza and Borrelia burgdorferi.16 note: 'Found by winnow, kev and lev in p010, p020, p021. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Conclusions quote: POTS is a rare dysautonomia that has been increasing in prevalence in the United States, and one of the causes of POTS may be post-viral neuropathy. note: 'Found by winnow, kev and lev in p001, p008, p020. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p008, p010, p012. Claude judged: supports.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: A range of diseases, including viral or bacterial infections, can cause POTS. Because an increasing number of patients who recovered from COVID-19 are now reporting POTS-like symptoms including brain fog, tachycardia and severe chronic fatigue, some experts believe coronavirus may be a trigger for POTS. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid34993433 cited: true text: full license: by-nc-nd verdict: supports section: Results > POTS onset and symptoms quote: 'More male than female patients experienced POTS onset within 3 months after a specific event (46.1% vs 40.9%, P = 0.02). The most common event preceding POTS onset was an infection (female patients: 42.1% vs male patients: 37.6%, P = 0.2).' note: 'Found by winnow, kev and lev in p020, p031. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Introduction quote: While the pathogenesis of PTS is heterogeneous, infection is a well-characterized trigger of PTS, with 28% reporting PTS onset following a viral prodrome. note: 'Found by winnow, kev and lev in p004, p002, p005. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Body quote: POTS is known to be triggered by viral and bacterial infections, such as influenza and Epstein-Barr virus.12 In addition, there are case reports of individuals developing symptoms of and fulfilling the diagnostic criteria for POTS 6 to 8 months following recovery from COVID-19 infection.13 note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Epidemiology & natural history quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p001, p008. Claude judged: supports.' - paper: pmid33786700 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33786700. Found by winnow, kev and lev in p016, p004, p006. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Introduction quote: Although the mechanisms for the development of POTS are not well-understood, patients with POTS often report experiencing a trigger such as a viral illness, electrical injury, lightning injury, gastric bypass surgery, or traumatic brain injury weeks to months prior to the onset of symptoms.5–7 note: 'Found by winnow, kev and lev in p001, p005, p011. Claude judged: supports.' - paper: pmid32880754 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p010, p009. Claude judged: supports.' - paper: pmid29343965 cited: true text: full license: by-nc verdict: supports section: Introduction quote: The onset of POTS symptoms may be gradual and can be triggered by an infective illness. note: 'Found by winnow, kev and lev in p002, p010. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Typical Presentations of POTS > Triggering Conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p035, p037. Claude judged: supports.' - paper: pmid39775762 cited: true text: abstract license: none verdict: partial section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: partial.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: partial section: Postural Orthostatic Tachycardia Syndrome quote: There is strong evidence that SARS-CoV-2 may trigger POTS in patients with prolonged COVID-19 syndrome. note: 'Found by winnow, kev and lev in p061. Claude judged: partial.' - paper: pmid36575713 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36575713. Found by winnow, kev and lev in p003. Claude judged: partial.' - paper: pmid35056336 cited: true text: full license: by verdict: partial section: 4. Discussion quote: In the present study, in the long-haul COVID-19 patients with POTS, the orthostatic intolerance/POTS complaints began early after the start of the viral infection symptoms (1–3 weeks), consistent with other published case reports [5,7,9,56]. note: 'Found by winnow, kev and lev in p001, p031, p028. Claude judged: partial.' - paper: pmid34053992 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: We herein report a 25-year-old woman who developed new-onset postural orthostatic tachycardia syndrome (POTS) following COVID-19 infection without pneumonia. Three weeks after being diagnosed with COVID-19, she began experiencing fatigue, feeing unwell, intermittent palpitation, dyspnea and chest pain, especially while getting up from the sitting position. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - paper: pmid32848537 cited: true text: full license: by verdict: partial section: Discussion quote: A higher proportion of POTS patients reported symptoms of antecedent infections in our group of adolescents (60%) than previously described for adults (35%) (Kimpinski et al., 2012). note: 'Found by winnow, kev and lev in p039. Claude judged: partial.' - edge: - post_vaccination_onset - trigger_of - pots papers: 25 evidence: - paper: pmid39538129 cited: true text: full license: by-nc-nd verdict: supports section: Results > Clinical management quote: Several case reports and case series have illustrated the clinical manifestations and management of POTS following COVID-19 vaccination. Sanada et al. (2022) presented a 13-year-old male who developed myocarditis and POTS after receiving the second dose of the Pfizer-BioNTech vaccine, initially presenting with severe fatigue, headache, and sleep disturbances. note: 'Found by winnow, kev and lev in p021, p022, p023. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Not only does contracting SARS-CoV-2 infection confer the possibility of developing long COVID and subsequent development of POTS, but recipients of the SARS-CoV-2 vaccine have also been shown to develop POTS at a higher rate. The proposed explanation is that an immunological response was elicited by the administration of the vaccination, resulting in similar symptoms to long COVID. note: 'Found by winnow, kev and lev in p029, p034. Claude judged: supports.' - paper: pmid37650075 cited: true text: full license: by-nc verdict: supports section: Abstract > Discussion quote: The temporal association of POTS with the COVID-19 vaccination in a previously healthy patient and the lack of evidence of an alternative aetiology suggests COVID-19 vaccination is the potential cause of POTS in this patient. To our knowledge, this is the first case reporting severe, long-term, and treatment-refractory POTS following COVID-19 vaccination with mRNA1273. note: 'Found by winnow, kev and lev in p002, p003, p005. Claude judged: supports.' - paper: pmid36732397 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36732397. Found by winnow, kev and lev in p004, p005. Claude judged: supports.' - paper: pmid36530759 cited: true text: full license: none verdict: supports section: From the editor quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36530759. Found by winnow, kev and lev in p001, p003, p010. Claude judged: supports.' - paper: pmid36475233 cited: true text: full license: by verdict: supports section: Abstract quote: In this report, we present a case of myocarditis and POTS occurring in a 13-year-old male following COVID-19 mRNA vaccination. note: 'Found by winnow, kev and lev in p002, p001, p006. Claude judged: supports.' - paper: pmid35891154 cited: true text: full license: by verdict: supports section: 3. Discussion quote: POTS has been reported post vaccination, such as for human papillomavirus vaccination and COVID-19 vaccination [21,22,23]. note: 'Found by winnow, kev and lev in p001, p008, p010. Claude judged: supports.' - paper: pmid35725868 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35725868. Found by winnow, kev and lev in p001, p002, p006. Claude judged: supports.' - paper: pmid35062788 cited: true text: full license: by verdict: supports section: 1. Introduction quote: New-onset POTS was judged as “definitely associated” and was increased by the HPV vaccines (3675 vs. 3352, RR 1.08 (95% CI 1.01 to 1.15), NNH 144, p = 0.03, I2 = 29%) [16]. note: 'Found by winnow, kev and lev in p021, p001, p002. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Discussion quote: It is postulated that disruption of the body’s autonomic nervous system in POTS has potential triggers from viral infections and vaccines. De novo POTS is noted in a number of cases post-vaccination of HPV. note: 'Found by winnow, kev and lev in p001, p005, p008. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: partial section: 3. Discussion quote: Case reports have documented adolescent girls developing symptoms of orthostatic intolerance and excessive tachycardia consistent with POTS in the days and weeks following Gardasil immunization [10,11]. note: 'Found by winnow, kev and lev in p006, p009, p010. Claude judged: partial.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: While the vaccine has been shown to have numerous benefits in preventing severe illness from COVID-19, some patients have reported experiencing symptoms similar to Long-COVID after vaccination, including OI and POTS. In our study, two patients developed orthostatic symptoms following COVID-19 vaccination, and it is crucial to continue monitoring these individuals to assess the long-term effects of the vaccine on autonomic function. note: 'Found by winnow, kev and lev in p035. Claude judged: partial.' - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Secondary Postural Orthostatic Tachycardia Syndrome and Associated Disorders > Additional Associations and Postural Orthostatic Tachycardia Syndrome Mimickers > Human Papilloma Virus and COVID-19 Vaccination quote: Similarly, Kwan et al. reported increased odds of a new POTS diagnosis after COVID-19 vaccination in a cohort of 284,592 patients within 90 days of vaccination.[35] POTS-associated diagnoses were 1.52-fold more likely after than before COVID-19 vaccination, although significantly less likely than in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). note: 'Found by winnow, kev and lev in p041. Claude judged: partial.' - paper: pmid39109119 cited: true text: full license: by verdict: partial section: Discussion quote: This case presentation highlights a possible association between dTdap booster vaccination and the subsequent development of POTS in a 40-year-old female patient. The temporal relationship between vaccination and symptom onset, confirmed diagnosis via tilt table testing, absence of alternative etiologies, and concordance with typical POTS demographics strengthen the argument for a vaccine-adverse event (VAE). note: 'Found by winnow, kev and lev in p001, p004, p012. Claude judged: partial.' - paper: pmid38176772 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38176772. Found by winnow, kev and lev in p002, p006, p008. Claude judged: partial.' - paper: pmid37303827 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37303827. Found by winnow, kev and lev in p001, p002, p005. Claude judged: partial.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: 'Abstract > RESULTS:' quote: Additionally, it seems that POTS-like symptoms could be triggered after immunization with Pfizer- BioNTech, Moderna, and Oxford-AstraZeneca COVID-19 vaccines. note: 'Found by winnow, kev and lev in p016, p026, p004. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: However, there have been a few case reports published in peer-reviewed journals that show patients affected with POTS after receiving mRNA COVID-19 vaccination. The exact mechanism of action is not known at this time, but an autoimmune response to vaccination is one of the possible mechanisms. note: 'Found by winnow, kev and lev in p051. Claude judged: partial.' - paper: pmid36852364 cited: true text: full license: by verdict: partial section: Abstract quote: We present a case of a 15-year-old South Asian male who developed suspected postural orthostatic tachycardia syndrome (POTS) two weeks after receiving the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine booster, which was successfully managed with low-dose fludrocortisone and ivabradine. Clinicians should be aware of the Pfizer-BioNTech COVID-19 vaccine being implicated with the onset of POTS. note: 'Found by winnow, kev and lev in p001, p004, p010. Claude judged: partial.' - paper: pmid36718484 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: We also found three case reports of POTS after COVID-19 vaccination. Although causality between POTS and vaccines cannot be inferred from these cases, some vaccines are associated with various autoimmune neurological diseases such as Guillain-Barre syndrome or multiple sclerosis [37]. note: 'Found by winnow, kev and lev in p008, p013. Claude judged: partial.' - paper: pmid35870086 cited: true text: full license: none verdict: partial section: Patient 3 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p004, p005, p006. Claude judged: partial.' - paper: pmid35611338 cited: true text: full license: none verdict: partial section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35611338. Found by winnow, kev and lev in p005. Claude judged: partial.' - paper: pmid29876157 cited: true text: full license: by verdict: partial section: Review quote: According to Tomljenovic et al.'s case study in 2014, a young school girl presented with flu-like symptoms, such as a sore throat, low-grade fever, fatigue, swollen glands, and intense headaches two months after her human papilloma vaccine (HPV) injection. Her symptoms related to orthostatic intolerance worsened over time so much so that she had to go to school in a wheelchair due to chronic fatigue. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid26425598 cited: true text: full license: by verdict: partial section: Discussion > POTS, CFS, and the ASIA Syndrome quote: In conclusion, herein we described a case of disabling CFS/POTS secondary to qHPV Gardasil vaccination with symptom onset at 2 months following the second vaccine booster. note: 'Found by winnow, kev and lev in p001, p008, p018. Claude judged: partial.' - paper: pmid25882168 cited: true text: abstract license: none verdict: partial section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25882168. Found by winnow, kev and lev in p002, p001, p004. Claude judged: partial.' - edge: - long_covid - trigger_of - pots papers: 22 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Results > Newly diagnosed CAD following COVID-19 infection and vaccination quote: Following COVID-19 infection, 22 individuals were newly diagnosed with POTS, 12 with VVS, and 1 with delayed and 1 with transient OH, whereas in 39 cases presenting with new-onset OI the diagnostic workup excluded any CAD (i.e., OIw/oCAD). In most newly diagnosed CAD, the causal association with the passed COVID-19 infection was deemed probable (34 out of 36, 94%). note: 'Found by winnow, kev and lev in p022, p003, p036. Claude judged: supports.' - paper: pmid40734755 cited: true text: full license: by verdict: supports section: Abstract > Background quote: As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection. note: 'Found by winnow, kev and lev in p001, p008, p010. Claude judged: supports.' - paper: pmid39775762 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Long COVID-19 triggers an extended inflammatory response, characterized by the continuous production of cytokines and other inflammatory mediators [61]. This prolonged state of inflammation can lead to systemic effects, including damage to the vascular endothelium [62] and dysregulation of the ANS [63], creating fertile ground for the development of conditions such as POTS. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid38673062 cited: true text: full license: by verdict: supports section: 2. Pathophysiology > 2.2. Pathophysiology of Postural Orthostatic Tachycardia Syndrome > 2.2.4. COVID-19 and POTS quote: Not only does contracting SARS-CoV-2 infection confer the possibility of developing long COVID and subsequent development of POTS, but recipients of the SARS-CoV-2 vaccine have also been shown to develop POTS at a higher rate. note: 'Found by winnow, kev and lev in p029, p027. Claude judged: supports.' - paper: pmid38173173 cited: true text: full license: by-nc-nd verdict: supports section: Postural Orthostatic Tachycardia Syndrome quote: There is strong evidence that SARS-CoV-2 may trigger POTS in patients with prolonged COVID-19 syndrome. note: 'Found by winnow, kev and lev in p061. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: supports section: POTS and COVID-19 > Prevalence quote: Recently a case series study of 20 patients post-COVID-19 infection reports that almost a third of patients experience frequent autonomic symptoms like dizziness, syncope, and palpitations within 6–8 months of acute infection.16 Roughly 2–14% of survivors develop POTS, with another 9−61% who experience POTS-like symptoms within 6–8months.33 note: 'Found by winnow, kev and lev in p020, p021. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Abstract quote: The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. note: 'Found by winnow, kev and lev in p001, p008. Claude judged: supports.' - paper: pmid36590760 cited: true text: full license: by-nc verdict: supports section: Introduction quote: It is estimated that up to 3 million people in the United States may have had POTS before the pandemic but the prevalence is now significantly higher due to post-COVID POTS that may follow a SARS-CoV-2 infection as part of the post-acute sequelae of the virus.3 note: 'Found by winnow, kev and lev in p002. Claude judged: supports.' - paper: pmid36575713 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36575713. Found by winnow, kev and lev in p003. Claude judged: supports.' - paper: pmid36530759 cited: true text: full license: none verdict: supports section: The question quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36530759. Found by winnow, kev and lev in p001, p003, p005. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p010, p012, p026. Claude judged: supports.' - paper: pmid35056336 cited: true text: full license: by verdict: supports section: 4. Discussion quote: In the present study, in the long-haul COVID-19 patients with POTS, the orthostatic intolerance/POTS complaints began early after the start of the viral infection symptoms (1–3 weeks), consistent with other published case reports [5,7,9,56]. note: 'Found by winnow, kev and lev in p001, p028. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Introduction quote: In response, one author analysed how COVID-19 may mechanistically give rise to PTS.7 In this case series, we detail the clinical characteristics and treatment response of seven consecutive highly active young patients who developed PTS following infection with COVID-19. note: 'Found by winnow, kev and lev in p004, p002, p005. Claude judged: supports.' - paper: pmid34928881 cited: true text: full license: by verdict: supports section: Body quote: In addition, there are case reports of individuals developing symptoms of and fulfilling the diagnostic criteria for POTS 6 to 8 months following recovery from COVID-19 infection.13 It has been suggested that the risk of developing POTS post-COVID-19 is higher in those with a preexisting, underlying autoimmune and/or inflammatory process or in those with a history of concussion.12 note: 'Found by winnow, kev and lev in p007. Claude judged: supports.' - paper: pmid34053992 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: We herein report a 25-year-old woman who developed new-onset postural orthostatic tachycardia syndrome (POTS) following COVID-19 infection without pneumonia. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid33786700 cited: true text: full license: none verdict: supports section: Abstract > Conclusions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33786700. Found by winnow, kev and lev in p001, p004, p006. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Conclusion quote: Autonomic dysfunction presenting as POTS can be a delayed manifestation of COVID-19 infection. note: 'Found by winnow, kev and lev in p001, p011, p013. Claude judged: supports.' - paper: pmid32880754 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p002, p009, p010. Claude judged: supports.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 2. COVID-19-Related POTS > 2.2. Presumed Mechanism for COVID-19-Related POTS > 2.2.3. Direct Viral Infection quote: The COVID-19 virus can directly cause POTS symptoms (Figure 2). note: 'Found by winnow, kev and lev in p015. Claude judged: partial.' - paper: pmid37391116 cited: true text: full license: none verdict: partial section: 'Discussion > Central Illustration > COVID-19: a Trigger for Dysautonomia?' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 37391116. Found by winnow, kev and lev in p025, p029. Claude judged: partial.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: Because an increasing number of patients who recovered from COVID-19 are now reporting POTS-like symptoms including brain fog, tachycardia and severe chronic fatigue, some experts believe coronavirus may be a trigger for POTS. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - long_covid - trigger_of - postinfectious_evidence papers: 11 evidence: - paper: pmid41275041 cited: true text: full license: by verdict: supports section: Results > Newly diagnosed CAD following COVID-19 infection and vaccination quote: Following COVID-19 infection, 22 individuals were newly diagnosed with POTS, 12 with VVS, and 1 with delayed and 1 with transient OH, whereas in 39 cases presenting with new-onset OI the diagnostic workup excluded any CAD (i.e., OIw/oCAD). In most newly diagnosed CAD, the causal association with the passed COVID-19 infection was deemed probable (34 out of 36, 94%). note: 'Found by winnow, kev and lev in p003, p022, p036. Claude judged: supports.' - paper: pmid39775762 cited: true text: abstract license: none verdict: supports section: Abstract > Background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 39775762. Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Case presentation quote: A 39-year-old male with no significant past medical history presented with a 12-month history of sinus tachycardia and chest palpitations, which the patient reported started after infection with COVID-19. note: 'Found by winnow, kev and lev in p001, p008. Claude judged: supports.' - paper: pmid35853576 cited: true text: full license: none verdict: supports section: 'POTS: Prevalence, clinical presentation, and pathophysiology' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35853576. Found by winnow, kev and lev in p010, p012, p026. Claude judged: supports.' - paper: pmid34993394 cited: true text: full license: by-nc verdict: supports section: Introduction quote: In response, one author analysed how COVID-19 may mechanistically give rise to PTS.7 In this case series, we detail the clinical characteristics and treatment response of seven consecutive highly active young patients who developed PTS following infection with COVID-19. note: 'Found by winnow, kev and lev in p004, p002, p006. Claude judged: supports.' - paper: pmid34053992 cited: true text: full license: by-nc-nd verdict: supports section: Body quote: We herein report a 25-year-old woman who developed new-onset postural orthostatic tachycardia syndrome (POTS) following COVID-19 infection without pneumonia. Three weeks after being diagnosed with COVID-19, she began experiencing fatigue, feeing unwell, intermittent palpitation, dyspnea and chest pain, especially while getting up from the sitting position. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - paper: pmid33786700 cited: true text: full license: none verdict: supports section: Introduction quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 33786700. Found by winnow, kev and lev in p004, p006, p014. Claude judged: supports.' - paper: pmid33262898 cited: true text: full license: by verdict: supports section: Conclusion quote: Autonomic dysfunction presenting as POTS can be a delayed manifestation of COVID-19 infection. note: 'Found by winnow, kev and lev in p001, p013. Claude judged: supports.' - paper: pmid32880754 cited: true text: full license: none verdict: supports section: Body quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32880754. Found by winnow, kev and lev in p009, p010. Claude judged: supports.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports quote: Contemporary literature indicates potential links between viral infections and vaccines (particularly HPV) with the development of POTS.14,35,36 The earliest reports of a POTS-like syndrome in the aftermath of COVID-19 infection emerged in March 2020.37 note: 'Found by winnow, kev and lev in p020, p021. Claude judged: partial.' - paper: pmid35470419 cited: true text: full license: by-nc-nd verdict: partial section: Body quote: A range of diseases, including viral or bacterial infections, can cause POTS. Because an increasing number of patients who recovered from COVID-19 are now reporting POTS-like symptoms including brain fog, tachycardia and severe chronic fatigue, some experts believe coronavirus may be a trigger for POTS. note: 'Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - surgery_onset - trigger_of - pots papers: 5 evidence: - paper: pmid41561794 cited: true text: full license: by verdict: supports section: Abstract quote: A 39-year-old woman developed debilitating systemic symptoms following the placement of a synthetic mid-urethral sling for stress urinary incontinence. Previously in good health, she experienced sepsis and adrenal crisis immediately postoperatively, followed by persistent symptoms including fatigue, postural orthostatic tachycardia syndrome (POTS), neuropathic pain, cognitive dysfunction, autonomic instability, and recurrent infections. note: 'Found by winnow, kev and lev in p001, p015. Claude judged: supports.' - paper: pmid40729147 cited: true text: full license: by verdict: supports section: 1. Introduction quote: In some individuals, POTS may also emerge following significant physical or emotional stress, surgery, or pregnancy, indicating a potential link to bodily stressors and changes [8]. note: 'Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid33623665 cited: true text: full license: by-nc verdict: supports section: DISCUSSION quote: There has only been one case report in the literature reporting the development of POTS following thoracic surgery, involving a repair of an aortic coarctation [6]. Similarly, identified potential risk factors included surgery, prolonged bed rest, and use of antihypertensives that worsen orthostatic intolerance. note: 'Found by winnow, kev and lev in p010, p001, p007. Claude judged: supports.' - paper: pmid22889291 cited: true text: full license: by verdict: supports section: Abstract > Conclusion quote: This is the first reported case describing the occurrence of postural tachycardia syndrome after the surgical correction of an aortic coarctation. note: 'Found by winnow, kev and lev in p003, p001, p002. Claude judged: supports.' - paper: pmid39355826 cited: true text: full license: by verdict: partial section: Conclusion quote: POTS may occur after ablation in the AV junction. The mechanism is unknown and possibly related to the modulation of the ICNS from the radiofrequency energy application. note: 'Found by winnow, kev and lev in p008, p017. Claude judged: partial.' - edge: - physical_trauma_onset - trigger_of - pots papers: 4 evidence: - paper: pmid35647216 cited: true text: full license: by-nc verdict: supports section: Background quote: Moreover, concussion was found to be the second most common trigger preceding POTS onset in a group of 708 patients at a pediatric autonomic disorders clinic, second only to infection among the triggers assessed. note: 'Found by winnow, kev and lev in p004. Claude judged: supports.' - paper: pmid29864098 cited: true text: full license: by-nc-nd verdict: supports section: OVERVIEW OF POTS quote: In a retrospective study of 722 patients with POTS enrolled in a pediatric patient database, 11.4% of patients identified a temporal link to a concussive event precipitating their POTS symptoms.32 note: 'Found by winnow, kev and lev in p003, p012. Claude judged: supports.' - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Typical Presentations of POTS > Triggering Conditions quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p035. Claude judged: supports.' - paper: pmid20865679 cited: true text: abstract license: none verdict: supports section: Abstract > Results quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 20865679. Found by winnow, kev and lev in p003. Claude judged: supports.' - edge: - post_vaccination_onset - trigger_of - autoimmune_evidence papers: 3 evidence: - paper: pmid35870086 cited: true text: full license: none verdict: supports section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p004, p006, p012. Claude judged: supports.' - paper: pmid33968543 cited: true text: full license: by verdict: partial section: Discussion quote: This spike protein acts as an intracellular antigen, which in turn stimulates the immune system to form neutralizing antibodies that will block viral entry into host cells [18]. It is our speculation that the formation of antibodies triggers an autoimmune response that stimulates POTS disease, like it does in the patient in this case. note: 'Found by winnow, kev and lev in p008, p001, p011. Claude judged: partial.' - paper: pmid26425598 cited: true text: full license: by verdict: partial section: Discussion > POTS, CFS, and the ASIA Syndrome quote: In conclusion, herein we described a case of disabling CFS/POTS secondary to qHPV Gardasil vaccination with symptom onset at 2 months following the second vaccine booster. With the concurrent detection of elevated ANA, lupus anticoagulant, antiphospholipid, and subsequent diagnosis of Raynaud’s, this case fully meets the criteria for the recently identified ASIA syndrome (Table 2). note: 'Found by winnow, kev and lev in p001, p018, p008. Claude judged: partial.' - edge: - autoimmune_evidence - trigger_of - pots papers: 2 evidence: - paper: pmid33968543 cited: true text: full license: by verdict: supports section: Abstract quote: Postural orthostatic tachycardia syndrome (POTS) is an impaction of the autonomic nervous system initiating orthostatic tachycardia. There are numerous triggers for POTS including viruses, vaccines, and an autoimmune basis. note: 'Found by winnow, kev and lev in p001, p008, p011. Claude judged: supports.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: 'Abstract > RESULTS:' quote: Whilst the exact pathogenetic mechanism behind POTS is yet to elucidated, there has been increasing evidence pointing towards an autoimmune dysfunction. note: 'Found by winnow, kev and lev in p004, p019. Claude judged: partial.' - edge: - prolonged_bed_rest - trigger_of - pots papers: 2 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Exercise Physiology, Deconditioning, and POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051, p059. Claude judged: supports.' - paper: pmid33623665 cited: true text: full license: by-nc verdict: partial section: DISCUSSION quote: There has only been one case report in the literature reporting the development of POTS following thoracic surgery, involving a repair of an aortic coarctation [6]. Similarly, identified potential risk factors included surgery, prolonged bed rest, and use of antihypertensives that worsen orthostatic intolerance. note: 'Found by winnow, kev and lev in p010. Claude judged: partial.' - edge: - long_covid - trigger_of - autoimmune_evidence papers: 1 evidence: - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Moreover, the immune response to COVID-19 can lead to autoimmunity, where the body produces antibodies that mistakenly target the autonomic nervous system [60]. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - edge: - surgery_onset - trigger_of - autoimmune_evidence papers: 1 evidence: - paper: pmid41561794 cited: true text: full license: by verdict: supports section: Case Presentation quote: Given the timeline of symptom onset immediately after surgery, concerns were raised about the potential for an autoimmune syndrome triggered by the synthetic mesh of the urethral sling. note: 'Found by winnow, kev and lev in p001, p004. Claude judged: supports.' - edge: - post_vaccination_onset - trigger_of - hyperadrenergic_evidence papers: 1 evidence: - paper: pmid35870086 cited: true text: full license: none verdict: partial section: Patient 3 quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p005, p007. Claude judged: partial.' - edge: - long_covid - trigger_of - hypovolemic_evidence papers: 1 evidence: - paper: pmid39200375 cited: true text: full license: by verdict: supports section: 3. POTS Etiology and Its Complexity quote: Simultaneously, long COVID-19 can cause hypovolemia through various pathways, including decreased intake due to illness or direct viral effects on gastrointestinal systems leading to losses through diarrhea [64]. The resultant decrease in blood volume challenges the body’s ability to maintain adequate blood circulation, especially upon standing, which can trigger or exacerbate POTS symptoms. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - edge: - prolonged_bed_rest - trigger_of - hypovolemic_evidence papers: 1 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051. Claude judged: supports.' - edge: - deconditioning_evidence - trigger_of - pots papers: 1 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Cardiovascular Pathophysiology of POTS > Bedrest Causes POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p051. Claude judged: supports.' - edge: - hormonal_transition_onset - trigger_of - pots papers: 1 evidence: - paper: pmid36908200 cited: true text: full license: none verdict: partial section: 'Results: > Initial POTS onset during pregnancy:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36908200. Found by winnow, kev and lev in p030, p032. Claude judged: partial.' - edge: - hypermobility_heds - trigger_of - pots papers: 1 evidence: - paper: pmid40729147 cited: true text: full license: by verdict: partial section: Abstract quote: Additionally, a strong association between POTS and Ehlers–Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. note: 'Found by winnow, kev and lev in p001, p006. Claude judged: partial.' - edge: - mast_cell_activation - trigger_of - pots papers: 1 evidence: - paper: pmid35062788 cited: true text: full license: by verdict: partial section: 1. Introduction quote: We therefore hypothesize that in at least some patients who have suffered the onset of POTS following HPV vaccination, vaccination-induced worsening/escalation of previously unrecognized MCAS may be a key driver of PHPPV POTS—therefore the recognition and control of MCAS prior to vaccination might reduce AE risk. note: 'Found by winnow, kev and lev in p021, p007. Claude judged: partial.' - edge: - systemic_autoimmune_disease - trigger_of - pots papers: 1 evidence: - paper: pmid39678714 cited: true text: full license: by-nc verdict: partial section: Introduction quote: However, potential triggers include hereditary factors, underlying conditions such as diabetes, amyloidosis, sarcoidosis, cancer, or after a viral illness, traumatic event, pregnancy, or may be associated with autoimmune disorders such as lupus, Sjogren syndrome, and celiac disease. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - edge: - differential_syncope_oh - differential_diagnosis_of - pots papers: 19 evidence: - paper: pmid41767063 cited: true text: full license: by verdict: partial section: Differential Diagnosis quote: Differential diagnoses included OH, VVS, inappropriate sinus tachycardia (IST), psychogenic pseudosyncope (PPS), epilepsy, acute cerebrovascular disease, and primary cardiac disease. Although BP dropped during positional changes, syncope was not due to OH. note: 'Found by winnow, kev and lev in p014, p016. Claude judged: partial.' - paper: pmid39741599 cited: true text: full license: by verdict: partial section: Discussion quote: Given the complexity of the ANS and the potential for overlapping symptoms with other conditions, careful differentiation between POTS, other forms of OI, and other potential causes of dizziness and syncope is essential. note: 'Found by winnow, kev and lev in p036. Claude judged: partial.' - paper: pmid39202605 cited: true text: full license: by verdict: partial section: 3. Diagnosis of COVID-19-Related POTS quote: Typical differential diagnoses include vasovagal syncope, orthostatic hypotension, dehydration, syncope, inappropriate sinus tachycardia, chromaffinoma, anxiety, depression, and unrecognized drug-related side effects [30]. note: 'Found by winnow, kev and lev in p018, p020. Claude judged: partial.' - paper: pmid37519618 cited: true text: full license: by verdict: partial section: Case presentation quote: But in our patient, there was no fall in SBP or DBP, and HR increased by 35-40 bpm on head-up tilt. So OH was ruled out. note: 'Found by winnow, kev and lev in p007, p023. Claude judged: partial.' - paper: pmid37248893 cited: true text: full license: by-nc verdict: partial section: COVID-19 vaccination induced autoimmunity quote: Consider the difficulty faced by clinicians in distinguishing POTS from postural vasovagal syncope, a transient loss of consciousness caused by reduced cerebral blood flow. note: 'Found by winnow, kev and lev in p019. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Introduction > Definition of POTS quote: This must occur in the absence of orthostatic hypotension and without a clear alternative etiology. note: 'Found by winnow, kev and lev in p006, p008, p024. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: Orthostatic hypotension is already an exclusion criterion for the diagnosis of POTS. note: 'Found by winnow, kev and lev in p045, p039, p044. Claude judged: partial.' - paper: pmid36938206 cited: true text: full license: by verdict: partial section: Discussion quote: If findings are negative, a complete cardiological and neurological evaluation should be performed to rule out other causes of tachycardia, such as viral myocarditis and reflex syncope. Lastly, a tilt table test should be performed to rule out orthostatic hypotension before making the diagnosis of POTS. note: 'Found by winnow, kev and lev in p016. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Pediatric Considerations > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p188, p192, p042. Claude judged: partial.' - paper: pmid35818599 cited: true text: full license: by-nc-nd verdict: partial section: Differential Diagnosis quote: However, elevation of epinephrine and norepinephrine is atypical of POTS, as is the presence of orthostatic hypotension, which excludes the diagnosis of POTS. note: 'Found by winnow, kev and lev in p005, p003. Claude judged: partial.' - paper: pmid35742222 cited: true text: full license: by verdict: partial section: Abstract quote: The clinical characteristics of postural tachycardia syndrome and vasovagal syncope are similar but their treatments differ. Therefore, their differential diagnosis is important to guide the correct treatment. note: 'Found by winnow, kev and lev in p005, p001, p002. Claude judged: partial.' - paper: pmid35720084 cited: true text: full license: by verdict: partial section: The Role of Dysautonomia in the Clinical Course of COVID-19 > Dysautonomia in Post-COVID-19 Condition > Orthostatic Intolerance Syndromes > Postural Orthostatic Tachycardia Syndrome (POTS) quote: There may be an overlap between POTS and other disorders, in particular, orthostatic hypotension, vasovagal syncope, panic disorders, psychogenic pseudosyncope, chronic fatigue syndrome, Ehlers–Danlos syndrome, mast cell activation disorder and cardiac arrhythmias and should be considered in complex cases (71, 75). note: 'Found by winnow, kev and lev in p065, p068. Claude judged: partial.' - paper: pmid35372154 cited: true text: full license: by verdict: partial section: Introduction quote: Therefore, differentiating VVS from POTS is very important in clinical practice (4, 6). Currently, the differential diagnosis between these two diseases is mainly based on the clinical features and haemodynamic responses during the head-up tilt test (HUTT) (2, 7). note: 'Found by winnow, kev and lev in p001, p005, p007. Claude judged: partial.' - paper: pmid35288409 cited: true text: full license: by-nc-nd verdict: partial section: What other disorders can cause orthostatic intolerance? quote: Patients with orthostatic hypotension of 20 mm Hg or greater may have symptoms of orthostatic intolerance and may also have orthostatic tachycardia, but the presence of orthostatic hypotension precludes a diagnosis of POTS.6 note: 'Found by winnow, kev and lev in p012, p013, p008. Claude judged: partial.' - paper: pmid34928881 cited: true text: full license: by verdict: partial section: Body quote: The Canadian Cardiovascular Society (CCS) position statement on POTS further delineates that while sustained orthostatic hypotension within 3 minutes of standing precludes a diagnosis of POTS, transient initial orthostatic hypotension lasting less than a minute may occur in some patients with POTS.7 note: 'Found by winnow, kev and lev in p005, p023. Claude judged: partial.' - paper: pmid33150760 cited: true text: full license: by verdict: partial section: Discussion quote: After performing tilt table testing on a group of suspected POTS patients in this study, ten were found to have orthostatic hypotension and nine had syncope. In patients with orthostatic symptoms, tilt table testing is the preferred tool for differentiating between these types of orthostatic intolerance. note: 'Found by winnow, kev and lev in p027, p022. Claude judged: partial.' - paper: pmid32222376 cited: true text: full license: none verdict: partial section: POTS background quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 32222376. Found by winnow, kev and lev in p010, p028, p026. Claude judged: partial.' - paper: pmid27525257 cited: true text: full license: by verdict: partial section: 2. Methods > 2.2. Autonomic Cardiovascular Testing > 2.2.2. Postural Tachycardia Syndrome (POTS) quote: POTS is defined by the presence of orthostatic symptoms associated with an increment of heart rate by ≥30 BPM held for more than 30 seconds when changing position from supine to upright in the absence of orthostatic hypotension [7]. note: 'Found by winnow, kev and lev in p017, p010, p045. Claude judged: partial.' - paper: pmid21977261 cited: true text: full license: none verdict: partial section: DISCUSSION quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 21977261. Found by winnow, kev and lev in p017, p013, p019. Claude judged: partial.' - edge: - secondary_sinus_tachycardia - differential_diagnosis_of - pots papers: 13 evidence: - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 3. Diagnosis of COVID-19-Related POTS quote: Because symptoms associated with orthostatic tachycardia can occur in several diseases other than COVID-19-related POTS, other possible causes of orthostatic tachycardia should be excluded [31]. Blood laboratory examinations such as blood cell count, comprehensive metabolic panel, and thyroid function test can exclude non-cardiac causes of tachycardia such as hyperthyroidism and hypothyroidism. note: 'Found by winnow, kev and lev in p018, p019, p020. Claude judged: supports.' - paper: pmid37654428 cited: true text: full license: by verdict: supports section: 6. Diagnosis quote: In the differential diagnosis of POTS, it is important to exclude other causes of sinus tachycardia such as dehydration, hyperthyroidism, other viral infections, pulmonary embolism, cardiac disease, anxiety, anemia, metabolic disorders, deconditioning, or chronic fatigue syndrome (82). note: 'Found by winnow, kev and lev in p021, p022. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: supports section: Abstract quote: After ruling out the common causes of tachycardia and syncope, a diagnosis of POTS was established. note: 'Found by winnow, kev and lev in p001, p012, p013. Claude judged: supports.' - paper: pmid37261636 cited: true text: full license: by verdict: supports section: Methods > Patients and study design quote: Other causes of tachycardia, such as hypovolemia, cardiac diseases, hyperthyroidism, acute illness, severe deconditioning, infections or use of cardioactive drugs [20, 21] were excluded during the clinical examination process. note: 'Found by winnow, kev and lev in p009. Claude judged: supports.' - paper: pmid36938206 cited: true text: full license: by verdict: supports section: Discussion quote: If findings are negative, a complete cardiological and neurological evaluation should be performed to rule out other causes of tachycardia, such as viral myocarditis and reflex syncope. Lastly, a tilt table test should be performed to rule out orthostatic hypotension before making the diagnosis of POTS. note: 'Found by winnow, kev and lev in p016. Claude judged: supports.' - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 3. Diagnosis > 3.1 Diagnostic Criteria quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p004, p011. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Clinical Presentation of Postural Tachycardia Syndrome (POTS) > Diagnostic Criteria & Common Clinical Features quote: The syndrome must occur in the absence of prolonged bed rest, medications that impair autonomic regulation (such as vasodilators, diuretics, antidepressants or anxiolytic agents), or any other chronic debilitating disorders that might cause tachycardia (such as dehydration, anemia or hyperthyroidism). note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - paper: pmid40271232 cited: true text: full license: by verdict: partial section: Materials and methods quote: Patients could be included in our study only if they were seen by a neurologist at our institution, had a diagnosis of POTS, were between the ages of 18 and 50, had a positive tilt table test without orthostatic hypotension, had POTS symptoms for at least six months, and had a workup ruling out other causes of sinus tachycardia. note: 'Found by winnow, kev and lev in p012. Claude judged: partial.' - paper: pmid37204997 cited: true text: full license: by-nc verdict: partial section: Review of Clinical Reports > Diagnosis quote: Important differentials include, dehydration with associated orthostasis, neural-reflex syncope, inappropriate sinus tachycardia, phaeochromocytoma, psychiatric conditions, and often under-recognized medication related side effects.31 note: 'Found by winnow, kev and lev in p024, p027. Claude judged: partial.' - paper: pmid37009342 cited: true text: full license: by verdict: partial section: Review quote: Patients with dehydration usually present with an elevated heart rate, which could give a false-positive diagnosis of POTS. Therefore, we should avoid diagnosing POTS in patients with an acute or chronic diagnosis of dehydration, such as polyuria, vomiting, dehydration, etc. note: 'Found by winnow, kev and lev in p045, p046, p047. Claude judged: partial.' - paper: pmid36074973 cited: true text: full license: none verdict: partial section: 'Selected Etiology: Post-COVID-19 > Main Points:' quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 36074973. Found by winnow, kev and lev in p042, p108, p188. Claude judged: partial.' - paper: pmid35870086 cited: true text: full license: none verdict: partial section: Discussion quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 35870086. Found by winnow, kev and lev in p009. Claude judged: partial.' - paper: pmid30838497 cited: true text: full license: none verdict: partial section: Head-up tilt in the diagnostic evaluation of orthostatic intolerance quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30838497. Found by winnow, kev and lev in p063. Claude judged: partial.' - edge: - arrhythmia_differential - differential_diagnosis_of - pots papers: 3 evidence: - paper: pmid29523389 cited: true text: full license: none verdict: supports section: 3. Diagnosis > 3.1 Diagnostic Criteria quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 29523389. Found by winnow, kev and lev in p004, p011. Claude judged: supports.' - paper: pmid37519618 cited: true text: full license: by verdict: partial section: Case presentation quote: The differential diagnosis, in this case, was OH, vasovagal syncope (VVS), inappropriate sinus tachycardia (IST), neurally mediated syncope (NMS), and POTS. note: 'Found by winnow, kev and lev in p007, p001. Claude judged: partial.' - paper: pmid23270259 cited: true text: abstract license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 23270259. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - medication_induced_tachycardia - differential_diagnosis_of - pots papers: 3 evidence: - paper: pmid39202605 cited: true text: full license: by verdict: supports section: 3. Diagnosis of COVID-19-Related POTS > Differential Diagnosis quote: Certain drugs can trigger tachycardia, which may complicate the diagnosis of COVID-19-related POTS [52]. note: 'Found by winnow, kev and lev in p020. Claude judged: supports.' - paper: pmid37009342 cited: true text: full license: by verdict: supports section: Review quote: 'Medication-induced tachycardia: Several medications can induce tachycardia and lead to the misdiagnosis of POTS.' note: 'Found by winnow, kev and lev in p046, p037. Claude judged: supports.' - paper: pmid30838497 cited: true text: full license: none verdict: supports section: Head-up tilt in the diagnostic evaluation of orthostatic intolerance quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 30838497. Found by winnow, kev and lev in p063. Claude judged: supports.' - edge: - anxiety_depression - differential_diagnosis_of - pots papers: 2 evidence: - paper: pmid39559520 cited: true text: full license: by-nc verdict: partial section: Body quote: Diagnosis of POTS is often delayed due to a clinical presentation that includes a constellation of non-specific symptoms. These symptoms overlap with various other conditions, including anxiety and depression. note: 'Found by winnow, kev and lev in p007. Claude judged: partial.' - paper: pmid25156902 cited: true text: abstract license: none verdict: partial section: Abstract > Literature Review quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 25156902. Found by winnow, kev and lev in p003. Claude judged: partial.' - edge: - prolonged_bed_rest - differential_diagnosis_of - pots papers: 2 evidence: - paper: pmid34144933 cited: true text: full license: none verdict: supports section: Potential pathophysiological mechanisms quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 34144933. Found by winnow, kev and lev in p015, p007. Claude judged: supports.' - paper: pmid16943900 cited: true text: full license: by verdict: supports section: Clinical Presentation of Postural Tachycardia Syndrome (POTS) > Diagnostic Criteria & Common Clinical Features quote: The syndrome must occur in the absence of prolonged bed rest, medications that impair autonomic regulation (such as vasodilators, diuretics, antidepressants or anxiolytic agents), or any other chronic debilitating disorders that might cause tachycardia (such as dehydration, anemia or hyperthyroidism). note: 'Found by winnow, kev and lev in p005. Claude judged: supports.' - edge: - iron_deficiency - differential_diagnosis_of - pots papers: 1 evidence: - paper: pmid39559520 cited: true text: full license: by-nc verdict: supports section: Body quote: Diagnosis of POTS requires ruling out of other conditions with similar presentations, including thyroid disorders, adrenal gland disorders, anemia, iron deficiency, and electrolyte abnormalities, among many others.[6] note: 'Found by winnow, kev and lev in p008, p038. Claude judged: supports.' - edge: - systemic_autoimmune_disease - differential_diagnosis_of - pots papers: 1 evidence: - paper: pmid24819031 cited: true text: full license: none verdict: supports section: POTS > Diagnostic Evaluation of Possible POTS quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 24819031. Found by winnow, kev and lev in p074. Claude judged: supports.' - edge: - plasma_blood_volume_assay - measures - intravascular_volume papers: 1 evidence: - paper: pmid39614968 cited: true text: full license: by verdict: supports section: Introduction quote: Rebreathing small amounts of carbon monoxide (CO) offers a noninvasive, safe alternative to measure hemoglobin mass and blood volume. note: 'Found by winnow, kev and lev in p007, p038, p032. Claude judged: supports.' - edge: - active_stand_test - measures - orthostatic_heart_rate_increment papers: 1 evidence: - paper: pmid40003288 cited: true text: full license: by verdict: supports section: Abstract quote: AYAs showed significant reduction in active stand test heart rate increase (p < 0.001; d = 1.07) and maximum heart rate (p = 0.002, d = 0.76) from admission to discharge. note: 'Found by winnow, kev and lev in p001. Claude judged: supports.' - edge: - active_stand_test - part_of - autonomic_reflex_screen papers: 1 evidence: - paper: pmid38937334 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p001, p011. Claude judged: partial.' - edge: - valsalva_maneuver - part_of - autonomic_reflex_screen papers: 1 evidence: - paper: pmid38937334 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p001. Claude judged: partial.' - edge: - cerebral_blood_flow_measurement - part_of - orthostatic_challenge_testing papers: 1 evidence: - paper: pmid26909037 cited: true text: full license: by verdict: supports section: Discussion quote: To evaluate patients using the outlined classification, it is essential to monitor CBFv in addition to heart rate, blood pressure, and respiratory variables during the tilt test. note: 'Found by winnow, kev and lev in p013, p039. Claude judged: supports.' - edge: - valsalva_maneuver - part_of - orthostatic_challenge_testing papers: 1 evidence: - paper: pmid38937334 cited: true text: full license: none verdict: partial section: Abstract quote: null note: 'Quote withheld on the public site: the text has no open (CC) licence (a PubMed abstract or a full text without one). See PubMed 38937334. Found by winnow, kev and lev in p001. Claude judged: partial.' not_added: - edge: - hyperadrenergic_evidence - proposed_mechanism_of - autoimmune_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid24572257 - pmid29102451 - pmid31547749 - pmid32743496 - pmid33505857 - pmid35118574 - pmid35853576 - pmid36873318 - pmid40537187 - edge: - neuropathic_evidence - proposed_mechanism_of - autoimmune_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid29864098 - pmid36349067 - edge: - neuropathic_evidence - proposed_mechanism_of - cerebral_hypoperfusion_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid22783324 - edge: - arrhythmia_differential - proposed_mechanism_of - hyperadrenergic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid42299168 - edge: - cerebral_hypoperfusion_evidence - proposed_mechanism_of - neuropathic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid22783324 - pmid38390594 - edge: - gi_dysmotility - proposed_mechanism_of - neuropathic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid29549458 - edge: - hyperadrenergic_evidence - proposed_mechanism_of - neuropathic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid9868411 - edge: - hypovolemic_evidence - proposed_mechanism_of - postinfectious_evidence reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid34821709 - edge: - systemic_autoimmune_disease - proposed_mechanism_of - postinfectious_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid35288409 - edge: - active_stand_test - evidence_for - autoimmune_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid40537187 - edge: - genetic_testing - evidence_for - hyperadrenergic_evidence reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid11458707 - edge: - cardiac_mri - evidence_for - hypovolemic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid20579544 - edge: - cerebral_blood_flow_measurement - evidence_for - hypovolemic_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid39895557 - edge: - thermoregulatory_sweat_test - evidence_for - pots reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid36349067 - edge: - lifestyle_modification - indicates - cerebral_hypoperfusion_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid41301791 - edge: - lifestyle_modification - indicates - deconditioning_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid16943900 - edge: - auricular_vagus_nerve_stimulation - indicates - hyperadrenergic_evidence reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid37631004 - edge: - exercise_reconditioning - indicates - hypermobility_heds reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid36074973 - edge: - beta_blocker_therapy - indicates - long_covid reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid37209261 - edge: - exercise_reconditioning - indicates - postinfectious_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid29864098 - edge: - immunomodulatory_therapy - treats - anxiety_depression reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid38003876 - edge: - ivabradine_therapy - treats - mast_cell_activation reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid40627388 - edge: - cerebral_hypoperfusion_evidence - associated_with - differential_syncope_oh reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid35056406 - edge: - chronic_migraine - associated_with - hypermobility_heds reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid41924132 - edge: - hyperadrenergic_evidence - associated_with - physical_trauma_onset reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid29864098 - edge: - arrhythmia_differential - associated_with - postinfectious_evidence reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid40692561 - edge: - structural_cardiopulmonary_disease - associated_with - pots reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid29850268 - edge: - hypermobility_heds - associated_with - small_fiber_neuropathy_dx reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid41801611 - pmid42399338 - edge: - differential_syncope_oh - associated_with - structural_cardiopulmonary_disease reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid29850268 - edge: - gi_dysmotility - associated_with - systemic_autoimmune_disease reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid41952073 - edge: - hypermobility_heds - associated_with - systemic_autoimmune_disease reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid36908200 - pmid38673548 - edge: - postinfectious_evidence - associated_with - systemic_autoimmune_disease reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid34144933 - edge: - post_vaccination_onset - trigger_of - neuropathic_evidence reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid25990003 - edge: - gi_dysmotility - differential_diagnosis_of - pots reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid40856938 - edge: - hypermobility_heds - differential_diagnosis_of - pots reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid38176772 - pmid41020219 - edge: - long_covid - differential_diagnosis_of - pots reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid39741599 - edge: - cerebral_blood_flow_measurement - part_of - autonomic_reflex_screen reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid27525257 - edge: - head_up_tilt_test - part_of - autonomic_reflex_screen reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid34604136 - edge: - plasma_catecholamine_assay - part_of - autonomic_reflex_screen reason: All three models found it, but Claude judged that the paragraphs do not state it. papers: - pmid33886735 - edge: - active_stand_test - part_of - orthostatic_challenge_testing reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid34055686 - edge: - head_up_tilt_test - part_of - orthostatic_challenge_testing reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid40276022 - edge: - plasma_catecholamine_assay - part_of - orthostatic_challenge_testing reason: Claude confirmed it, but only in papers where lev did not find it (winnow and Kev did). papers: - pmid33740206