Postural Orthostatic Tachycardia Syndrome (POTS) is notoriously difficult to diagnose and successfully treat. POTS encompasses several different subtypes, but little research attention has focused on optimizing the diagnosis and treatment of specific subtypes. This study aims to identify variables potentially predictive of neuropathic POTS and determine which current medical therapies for POTS are most successful in the neuropathic population. Single-center retrospective review identified 382 patients diagnosed with POTS between 2018 and 2020. Diagnosis was established via the head-up tilt table test; neuropathic subtype was established via skin biopsy or quantitative sudomotor axon reflex test. Logistic regression identified variables predictive of the neuropathic subtype; Cox proportional hazard and Kaplan-Meier estimator modeling were employed to compare treatment response to medications between neuropathic and non-neuropathic patients. Patients with neuropathic POTS treated with ivabradine exhibited a median treatment response duration of 26.7 months in the neuropathic group vs. 10.7 months in the non-neuropathic group, reflecting a significantly reduced risk of treatment failure (hazard ratio = 0.273, = 0.028). No other studied treatments demonstrated different response. Of the clinical and demographic variables studied, only elevated baseline heart rate was significantly associated with the neuropathic POTS subtype, though with questionable clinical significance. Patients with neuropathic POTS may exhibit different medication treatment response compared to patients with non-neuropathic POTS, though prospective studies are needed for confirmation. Further study to identify optimal treatment regimens for different subtypes of POTS is a promising direction to improve the quality of care for patients with POTS.

Vaccination against high-risk HPV types is a key preventive measure. However, concerns regarding vaccine safety may hinder vaccination efforts. This study aims to evaluate adverse events (AEs) reported in the Vaccine Adverse Event Reporting System (VAERS) following HPV vaccination from 2006 to 2024, providing insights into its safety profile. We analyzed VAERS data, a spontaneous reporting system containing de-identified AE reports. Four disproportionality analyses (ROR, PRR, BCPNN, and MGPS) were applied, and adverse event signals were defined only when the positive criteria were simultaneously met across all four methods. Statistical analyses were performed using R software and Microsoft Excel, with a significance threshold of p < 0.05. A total of 77,909 HPV vaccine-related AE reports were analyzed, with 68.4% involving females and 48.7% affecting individuals under 18. Serious AEs accounted for 11,659 reports, with headache and fatigue being the most common. Syncope was the most frequent signal, while postural orthostatic tachycardia syndrome (POTS) exhibited the strongest signal strength. Approximately 90% of AEs occurred within 30 days post-vaccination. Among vaccine types, HPV4 had the highest number of reports, and intramuscular injection was the most common administration route. This study offers an updated pharmacovigilance assessment of adverse events reported following HPV vaccination, highlighting reported patterns and statistical signals that may warrant further investigation.

A significant number of physicians are unclear of the vast clinical manifestations of dysautonomia and imbalance of the autonomic nervous system, specifically the parasympathetic and sympathetic nervous systems. The major obstacle has been an inability to determine the mechanism of action as well as multisystem dysfunction and a lack of clear-cut testing. Dysautonomia, a pathophysiological malfunction of the sympathetic and parasympathetic nerves in our bodies, can present as altered clinical functions of heart rate (tachycardia/bradycardia), altered breathing patterns, blood pressure (hypertension/hypotension), sweating, digestion, syncope, etc. These symptoms have caused specialists to miss this diagnosis because of relative nonspecificity. Our current analysis of patients demonstrates significant delays in diagnosis, misdiagnosis, and the development of chronic syndromes because of the above. We demonstrate that monitoring of heart rate and blood pressure with changes in position and respiration can be easily and quickly performed without orthostatic stress and can demonstrate the entities of sympathetic withdrawal, cholinergic excessive aspects as well as tachycardia, blood pressure dips with posture, etc. This analysis takes less than an hour without the need for injections or medication, thus more quickly informing the cardiologist/neurologist of the correct diagnosis. We will attempt to demystify these issues so that clinicians and the scientific community will have a better understanding of this entity and consider a diagnosis of dysautonomia earlier in the differential diagnostic process and start treatment approaches sooner.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disorder characterized by excessive increases in heart rate upon standing and poor orthostatic tolerance. Impairments in large artery, endothelial, and venous function may collectively, or individually, result in excessive blood pooling and impaired venous return, or other inadequate vascular response to standing, thus contributing to POTS. Herein, we tested the hypothesis that patients with POTS would exhibit reduced large artery stiffness, enhanced endothelial function, and greater lower limb venous pooling while standing, compared with healthy controls. Fourteen participants with a clinical diagnosis of POTS and 15 age-matched controls (all females; median age [interquartile range]; 21 [19-37] yr, = 0.769) were recruited. Central arterial stiffness was determined using carotid-femoral pulse wave velocity (cfPWV; SphygmoCor). Endothelial function was assessed using brachial artery flow-mediated dilation (FMD) following a 5-min forearm occlusion at 200 mmHg. Functional measures of calf venous volume and filling time (90% maximal venous filling) were acquired (air plethysmography) while standing. cfPWV was increased in people with POTS [(means ± SD) 5.5 ± 0.9 vs. 4.8 ± 0.4, = 0.031], whereas FMD was not different between groups ( = 0.854). During standing, calf venous volume was 29% greater in people with POTS ( = 0.048), and venous filling time was almost twice as long (404 ± 199 vs. 207 ± 99 s; = 0.003). These findings indicate that people with POTS exhibit increased central arterial stiffness, preserved endothelial function, and increased calf venous filling during standing. Such differences in lower limb venous filling dynamics on standing likely contribute to the orthostatic intolerance that characterizes POTS. Females with POTS and age-matched healthy controls underwent assessments of central arterial stiffness, endothelial function, and calf distensibility. Pulse wave velocity was higher in people with POTS, but brachial artery flow-mediated dilatation was not different between groups. Standing calf volume was greater in people with POTS, and maximal filling times were twice as long, suggesting altered venous and/or microvascular function. Augmented venous pooling in patients with POTS may impair venous return and orthostatic tolerance.

Autoimmune autonomic disorders are common, though often under-recognized, and suboptimally understood. Autonomic nervous system impairment may result from immune-mediated damage to central or peripheral autonomic pathways, and typically involve both sympathetic and parasympathetic systems, as well as the enteric nervous system. Various autoimmune conditions may primarily involve the autonomic nervous system, as in autoimmune autonomic ganglionopathy associated with ganglionic nicotinic acetylcholine receptor antibodies or may involve autonomic systems as part of a multisystem neurologic process with or without underlying malignancy, or autonomic nerves may be targeted in systemic autoimmunity as is seen with Sjögren's syndrome. A careful history and diagnostic evaluation is necessary to determine the type, distribution, and severity of dysautonomia; which may be generalized or more restricted in nature. An understanding of potential autonomic features in the various autoimmune autonomic disorders can help to provide diagnostic clarity, and recognition of autonomic signs and symptoms is necessary to direct symptomatic and immunotherapeutic decisions in these patients.

Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are relatively common and disabling multisystem disorders that share overlapping features, including post-infectious onset and similar clinical manifestations such as brain fog, fatigue, muscle pain, and dysautonomia with orthostatic intolerance. These similarities suggest that Long COVID and ME/CFS may share common pathophysiological mechanisms, though the underlying mechanisms remain poorly understood, partly due to the difficulty in quantifying many of the symptoms. This retrospective study evaluated Long COVID and pre-COVID ME/CFS patients who completed autonomic testing between 2018 and 2023 at the Brigham and Women's Faulkner Hospital Autonomic Laboratory. The evaluations included autonomic tests (Valsalva maneuver, deep breathing, tilt-table test, and sudomotor function) with capnography and transcranial Doppler monitoring of cerebral blood flow velocity (CBFv) in the middle cerebral artery, neuropathic assessment through skin biopsies for small fiber neuropathy (SFN), invasive cardiopulmonary exercise testing (ICPET), and laboratory analyses covering metabolic, inflammatory, autoimmune, and hormonal profiles. A total of 143 Long COVID and 170 ME/CFS patients were analyzed and compared to 73 healthy controls and 290 patients with hypermobile Ehlers-Danlos syndrome (hEDS). Tests revealed extensive similarities between Long COVID and ME/CFS, including reduced orthostatic CBFv (92%/88% in Long COVID/ME/CFS), mild-to-moderate widespread autonomic failure (95%/89%), presence of SFN (67%/53%), postural tachycardia syndrome (POTS) (22%/19%), neurogenic orthostatic hypotension (15%/15%) and preload failure (96%/92%, assessed in 25/66 Long COVID/ME/CFS). Patients with hEDS exhibited more severe peripheral neurodegeneration compared to the other groups. Laboratory tests did not distinguish between the conditions. Both Long COVID and ME/CFS demonstrate dysregulation in cerebrovascular blood flow, autonomic reflexes, and small fiber neuropathy, suggesting that these conditions may share a common underlying pathophysiology. However, differing distributions of findings in patients with hEDS raise the question of whether these conditions represent distinct but overlapping syndromes or reflect a shared underlying pathway. Further research is required to clarify the relationship between these conditions and the potential underlying pathophysiological mechanisms.

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic disorder characterized by chronic (> 3 months) orthostatic intolerance and an increase in heart rate (HR) of ≥ 30 beats per minute (bpm) without orthostatic hypotension. Traditional diagnostic approaches, such as the active standing or tilt-table test, are typically conducted under controlled clinical conditions, limiting their ability to capture the natural variability of symptoms and the intricate physiological responses occurring in daily life. These tests may cause patient discomfort, dizziness, nausea, or syncope. Furthermore, they are timeconsuming and cannot be used as a screening tool for POTS. To address these limitations, this study explored wearable devices that continuously collect physiological data-specifically, electrocardiogram (ECG) and accelerometer (ACC)-derived metrics-from POTS patients and healthy controls during routine daily activities. Physiological features around posturechange events identified in the data were processed and used to train and test a baseline deep learning model. The model demonstrated promising performance in accurately differentiating POTS patients from healthy controls in a relatively small cohort (66 from POTS patients and 20 from controls), indicating its potential as a feasibility study for clinical decision support. Future studies involving larger and more diverse samples under varying clinical conditions would be necessary to enhance the robustness and viability of our diagnostic model.

Abdominopelvic Vascular Compression Syndrome(s) (VCS) are rare disorders with diverse symptoms that appear to occur more frequently in patients with Ehlers-Danlos Syndrome (EDS) and Hypermobility Spectrum Disorder (HSD). 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. This review summarises the established literature on this complex topic, highlighting these relationships, with the aim to propose a framework for recognising and managing VCS among patients with EDS/HSD. Given the limited body of literature on this topic, we also aim to underscore the need for further research within this specific patient population. A PRISMA-guided systematic review was conducted using PubMed and Ovid/Medline databases. VCS included Median Arcuate Ligament Syndrome (MALS), Superior Mesenteric Artery Syndrome (SMAS), Nutcracker Syndrome (NCS), and May-Thurner Syndrome (MTS). Given the limited number of studies, small cohort studies and case reports/series were also reviewed. Of 183 screened studies, 62 met the inclusion criteria. Only six studies directly addressed the VCS in EDS/HSD. Five discussed an EDS-POTS association, two described links between MCAS, POTS, and EDS, and five associated POTS with VCS. Only one study explored all four conditions. Evidence suggests an association between EDS/HSD, VCS, POTS, and MCAS but remains limited. Underdiagnosis and delayed treatment are common and underscore the need for multi-disciplinary care. Invasive imaging and interventions appear generally safe in EDS/HSD, excluding vascular EDS, yet robust safety and outcome data and tailored diagnostic or treatment algorithms are lacking and require further investigation.

The aim of the study was to clarify the cause of orthostatic dysregulation in Japanese children by analyzing fluctuations in adenylate cyclase activity. Four types of orthostatic dysregulation in Japan include postural orthostatic tachycardia syndrome, delayed orthostatic hypotension, immediate orthostatic hypotension, and vasovagal syncope. However, the exact cause of these disorders remains unknown. To identify the cause of these conditions, we examined the resting blood adenylate cyclase activity and basic clinical data (blood pressure, pulse rate) of 30 patients diagnosed with orthostatic dysregulation (21 postural orthostatic tachycardia syndrome, eight delayed orthostatic hypotension, one immediate orthostatic hypotension, zero vasovagal syncope) and 20 previously reported healthy adults. The results of this study showed that adenylate cyclase activity (isoproterenol and adrenaline) in patients with postural orthostatic tachycardia syndrome was significantly higher than that in patients with delayed orthostatic hypotension and healthy adults. Moreover, patients with postural orthostatic tachycardia syndrome had significantly higher values than healthy adult controls at all five concentration points. Adenylate cyclase activity in patients with delayed orthostatic hypotension showed a trend toward higher values at 10 μM of adrenaline. Furthermore, owing to the higher adenylate cyclase activity in patients with postural orthostatic tachycardia syndrome, their systolic blood pressure was higher than that in patients with delayed orthostatic hypotension. These results suggest that increased adenylate cyclase activity may be related to the onset of orthostatic dysregulation (postural orthostatic tachycardia syndrome and delayed orthostatic hypotension). In conclusion, adenylate cyclase activity levels may be related to the onset of orthostatic dysregulation, and this can be used as a new strategy for diagnosing orthostatic dysregulation.

hypermobile spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are connective tissue disorders often associated with systemic manifestations such as mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS), irritable bowel syndrome (IBS), and autoimmune conditions, including spondyloarthritis (SpA). The overlap of these conditions complicates diagnosis and treatment. This study investigates the prevalence of MCAS and other comorbidities, as well as patterns of medication use, in individuals with HSD/EDS. this cross-sectional study included 37 participants diagnosed with HSD or EDS based on the 2017 Diagnostic Consensus Criteria. Participants were divided into two groups: 23 with SpA + EDS and 14 with EDS-only. Demographic variables, comorbidities, and medication use (biologics, disease-modifying antirheumatic drugs [DMARDs], and nonsteroidal anti-inflammatory drugs [NSAIDs]) were analyzed using comparative statistical methods. MCAS was significantly less prevalent in SpA + EDS participants (13%) compared to the EDS-only group (85.7%, p < 0.0001). POTS (60.9% vs 78.6%) and IBS (60.9% vs 85.7%) occurred at similar frequencies in both groups. The use of immunomodulators was higher in SpA + EDS (73.9%) than EDS-only (42.8%, p = 0.003). Biologic use was more common in SpA + EDS (34.8% vs 7.1%, p = 0.050), whereas NSAID use was higher in EDS-only participants (47.4% vs 30.4%, p > 0.05). the lower MCAS prevalence in SpA + EDS may reflect symptom overlap or suppression due to immunomodulatory treatments. Differences in medication use highlight variations in diagnostic and therapeutic strategies. Comprehensive evaluations are essential to ensure accurate diagnoses and optimal treatment approaches.

The combination of neurological, cardiac, and pulmonary disease in patients with systemic sclerosis (SS) is rare. The aim of the study was to report a patient with SS who manifested with migraine without aura, Raynaud's phenomenon, pulmonary hypertension, and postural tachycardia syndrome (POTS), a combination which has not been previously reported. The patient is a 53-year-old Caucasian woman with diffuse cutaneous SS who was treated with methotrexate and developed migraine without aura since the age of 6 years. Since age 31 years, she developed Raynaud's phenomenon with several attacks daily, which could be triggered by cold and also occurred in summer. At the age of 52 years, pulmonary fibrosis with secondary pulmonary hypertension was diagnosed and bosentan was administered. At the age of 53 years, POTS was diagnosed. The frequency of migraine was one per week at the age of 53 years. This case shows that migraine can be the initial manifestation of diffuse cutaneous SS, followed by Raynaud's syndrome, pulmonary hypertension and POTS.

Postural tachycardia syndrome (POTS) is a common, often disabling disorder of autonomic nervous system regulation without a unifying etiological account. Converging evidence suggests infectious, physical, and emotional threats frequently precede onset. We propose a hypothesis-generating model in which POTS may, in some individuals, involve threat-induced, centrally maintained disruption of brain-body communication that may be responsive to neuroplasticity-based behavioral medicine. In this paper, we synthesized multidisciplinary literature and our team's data spanning (a) autonomic and central nervous system responses to threat and trauma, (b) neurological alterations associated with early life stress, (c) links between adverse childhood experiences and posttraumatic stress disorder with autonomic symptom burden, and (d) clinical developments targeting the threat system and autonomic regulation. These data suggest that chronic or overwhelming threat exposure is associated with sympathetic activation, reduced vagal tone, and neuroplastic alterations within cortico-limbic and brainstem networks that parallel POTS features (exaggerated tachycardia, autonomic rigidity, multisystem dysregulation). Preliminary data indicate individuals with higher trauma exposure and PTSD symptoms report greater autonomic symptom severity and poorer global health. Emerging imaging suggests a potentially important role for the periaqueductal gray (PAG), a midbrain hub for autonomic, cardiovascular, motor, and pain responses to threat, which may fail to reset after trauma, leaving the ANS in a sustained escape-mode (fight/flight/freeze) that increases POTS risk. Overall, these findings provide preliminary conceptual support for a unified hypothesis linking trauma, PAG-mediated threat responses, and sustained autonomic dysregulation in POTS, underscoring the importance of trauma-informed care. Behavioral interventions that target threat reduction and autonomic regulation such as rate variability biofeedback and neuroplasticity-oriented psychotherapies, may complement standard medical care. Prospective, longitudinal studies are needed to clarify causal pathways and identify responsive subgroups, and randomized clinical trials are required to establish the efficacy of nervous system-focused behavioral interventions.

Anterior cervical discectomy and fusion (ACDF) surgery is a treatment for cervical disk herniation, a condition that may contribute to compression upon the spinal cord or the exiting nerve roots. The primary goals of this surgery are to decompress the neurological structures while stabilizing segments that are either unstable intrinsically or unstable by way of decompression. More recently, total disk arthroplasty (TDA) and anterior decompression has been introduced as an alternative to ACDF. Pneumothorax is caused by air filling the pleural cavity between the parietal pleura and the lung, causing the lung to collapse from the loss of negative pressure in that space, impairing lung function. The development of pneumothorax is a rare event during anterior approaches to the cervical spine, but the authors are not aware of the development during surgery of a pneumothorax contralateral to the side of approach. A 27-year-old female patient with cervical disc disease associated with C5-C6 and C6-C7. The patient has a history of smoking, an incomplete right bundle branch block, postural orthostatic tachycardia syndrome, premature ventricular contraction, and fibromyalgia, presented to the operating room for anterior decompression and TDA of C5-C6 and C6-C7 for cervical disk disease. There was no history of soft tissue disease. During anterior cervical spine surgery, contralateral pneumothorax can occur. This may happen due to the 30-degree positioning, positive pressure ventilation with positive end-expiratory pressure/continuous positive airway pressure, and potential pressure differential separating the tracheoesophageal complex from the pre-vertebral potential space. There are no current preventative measures for pneumothorax during anterior cervical spine surgery with standard techniques, but it is important not to dismiss the condition based solely on initial negative imaging results. Spontaneous contralateral pneumothorax is not commonly recognized as a complication of anterior cervical spine surgery; however, physicians should be aware of the possibility of its occurrence.

COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects. We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites ( ≤ 0.05) using molecular descriptors. Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC. By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes.

Background Ehlers-Danlos syndrome (EDS) encompasses a group of connective tissue disorders often extending beyond musculoskeletal involvement. Emerging evidence indicates a high prevalence of cardiovascular autonomic dysfunction in this population, yet systematic physiologic evaluations remain limited. Objective To characterize cardiovascular autonomic function in EDS using standardized autonomic testing and heart rate variability (HRV) indices, and to explore intrinsic autonomic coupling by correlating resting heart rate with HRV parameters. Methods This cross-sectional study included 30 clinically diagnosed patients with EDS and 30 age- and sex-matched healthy controls. Short-term HRV analysis (five-minute supine ECG) and standard autonomic testing, including head-up tilt, were performed under controlled laboratory conditions. HRV indices were derived using Fast Fourier Transform (FFT) algorithms. Group differences were evaluated with independent t-tests, and correlations between resting heart rate and HRV measures were analyzed using Pearson's correlation. Results Compared with controls, patients with EDS exhibited higher resting heart rate (87.3±11.6 vs 75.2±9.8 bpm), lower parasympathetic time-domain indices (standard deviation of normal-to-normal intervals or SDNN 35.4±9.7 vs 49.1±11.4 ms; root mean square of successive differences (RMSSD; 20.7±6.9 vs 31.6±8.8 ms), and altered frequency-domain markers (low frequency (LF) power 671±205 vs 542±176 ms²; high frequency (HF) power 174±81 vs 272±106 ms²; LF/HF ratio 3.7±1.3 vs 1.8±0.7). Orthostatic intolerance was observed in 16 (53.3%) of the patients with EDS versus three (10%) of the controls. Correlation analysis revealed that in EDS, resting HR correlated negatively with SDNN (r=-0.45, p=0.01), RMSSD (r=-0.52, p<0.01), and HF power (r=-0.39, p=0.03), while showing a positive correlation with LF/HF ratio (r=0.58, p<0.001). Conclusion Patients with EDS had autonomic dysregulation, with sympathetic predominance and diminished vagal modulation. The intrinsic coupling between resting heart rate and HRV indices suggests impaired cardiovascular autonomic integration. HRV profiling is a valuable noninvasive biomarker for early identification and longitudinal monitoring of autonomic dysfunction in EDS, potentially enhancing disease characterization and guiding individualized therapeutic strategies.

GARDASIL 9, a 9-valent HPV vaccine approved in 2014, is widely administered for the prevention of HPV-related malignancies. Although clinical trials demonstrated a favorable safety profile, rare or delayed-onset adverse events may not be captured pre-licensure. Post-marketing surveillance using VAERS offers a complementary approach for signal detection and safety monitoring. We conducted a retrospective pharmacovigilance analysis of VAERS reports following GARDASIL 9 administration from January 1, 2015 to December 31, 2024. Adverse events were encoded using MedDRA v26.0 and categorized by System Organ Class. Disproportionality analyses using four independent algorithms (ROR, PRR, IC, EBGM) were applied to identify positive safety signals. Subgroup assessments included serious reports, death reports, and reports in pregnant individuals. Among reported events, most were non-serious and consistent with known reactogenicity patterns, including syncope, headache, and injection site reactions. However, signals were also detected for certain events not listed in product labeling, including postural orthostatic tachycardia syndrome, eye movement disorder, autoimmune thyroiditis, and posture abnormality. In 57 death reports, neurological terms showed signal elevation but lacked consistent etiologic patterns. No positive signals were detected in the 18 pregnancy-associated reports. This VAERS-based analysis supports the established safety of GARDASIL 9 while highlighting rare signals that warrant further investigation. Given the limitations of passive surveillance, integration with active monitoring systems is essential to refine safety profiles and support ongoing public health vaccination efforts.

Children and adolescents commonly experience orthostatic intolerance associated with impaired participation and quality of life. We aimed to characterize autonomic responses to provoked presyncope in children with recurrent presyncope/syncope and healthy adolescents. We determined orthostatic tolerance (OT, time to presyncope [mins]) in 36 pediatric patients (age 15 ± 3 yrs., 26 female) with recurrent presyncope/syncope, and 17 asymptomatic controls (age 13 ± 3 yrs., 8 female), using a tilt test with graded lower body negative pressure. Cardiovascular parameters, forearm vascular resistance (FVR), mean middle cerebral artery velocity (MCAv), and breath-by-breath end tidal gases were continuously monitored. Responses to the Valsalva maneuver (VM), cerebral autoregulation, and cerebral reactivity to carbon dioxide were also determined. OT was similar in pediatric patients (21 ± 1.5 min) and controls (20 ± 2.0 min, p = 0.74), but smaller than adult reference values (33.8 ± 0.8 min, p < 0.01). Tilting decreased systolic arterial pressure in pediatric patients (p = 0.009), but not pediatric controls (p = 0.12). Tilting decreased MCAv (p = 0.002) in pediatric patients, with impairments in cerebral autoregulation (p = 0.02) that were negatively correlated with OT (r = -0.322; p = 0.024). Both pediatric patients (+48.9 ± 8.0 %) and controls (+36.7 ± 14.7 %) had small FVR responses compared to adult reference data (+100 ± 12 %, p < 0.01). Blood pressure responses to the VM were abnormal in pediatric patients, with a lower nadir in mean arterial pressure (81.7 ± 2.0 mmHg) compared to pediatric controls (94.0 ± 2.8 mmHg, p = 0.001). Pediatric patients with recurrent presyncope/syncope had impaired orthostatic cardiovascular and autoregulatory responses compared to pediatric controls. Sympathetically-mediated responses were small in children, underscoring the need for pediatric-specific standards for orthostatic cardiovascular control, and treatments targeting enhancement of vascular resistance in children with syncope.

Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos syndrome (h-EDS) are multisystemic connective tissue disorders involving joint hypermobility and numerous other manifestations. Autonomic dysfunction, chronic pain, and chronic fatigue are known comorbidities of HSD and h-EDS that can affect patient quality of life (QoL), but there are limited data on the severity of autonomic symptoms, prevalence of comorbid conditions and QoL in patients with HSD/h-EDS. We utilized the Composite Autonomic Symptom Scale (COMPASS-31) to assess autonomic symptom severity, Short-Form 36 (SF-36) to assess QoL, and the Beck Depression Inventory Second Edition (BDI-II) in a cohort of women with physician-diagnosed HSD or h-EDS, who completed these questionnaires anonymously. 84 women (mean age of 37.1 ± 8.4 years) completed the study. 58.3 % reported having physician-diagnosed postural orthostatic tachycardia syndrome (POTS), 32.1 % had mast cell activation syndrome (MCAS), 54.8 % had migraine, 26.2 % had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and 98.8 % reported experiencing chronic pain. Importantly, 25 % of patients reported having all three diagnoses: HSD/h-EDS, POTS and MCAS. Mean COMPASS-31 score was 54.45 (range 18.79-80.93), indicating severe autonomic dysfunction, which was significantly higher than in patients with multiple sclerosis, diabetic neuropathy, scleroderma, and psoriatic arthritis as shown in prior studies. Mean SF-36 score was 32.38 (SD = 22.91) indicating poor QoL, which was worse than in patients with POTS, multiple sclerosis, rheumatoid arthritis, and lupus as determined by prior studies. This study demonstrates that women with HSD/h-EDS experience severe autonomic dysfunction, chronic pain, chronic comorbid conditions and reduced QoL. More than half of participants in this cohort had POTS and migraine, with one in four having a clinical triad of HSD/h-EDS, POTS and MCAS.

To determine the prevalence of autonomic symptoms in post-treatment Lyme disease (PTLD) and identify clinical factors that associate with abnormal hemodynamics on the 10-minute active stand test. We administered the Composite Autonomic Symptom Score-31 survey to 37 patients with PTLD and compared them with a cohort of patients with postural orthostatic tachycardia syndrome (POTS) without a known history of Lyme disease. We also report the 10-minute active stand test performed in 210 patients with PTLD recruited from July 1, 2016 through October 31, 2024. Patients with PTLD had higher total Composite Autonomic Symptom Survey 31 scores than healthy controls and reported similar vasomotor, urinary, and pupillomotor symptom burden as patients with POTS. On the 10-minute active stand test, 9 of the 210 (4.29%) patients with PTLD had orthostatic tachycardia. Although the prevalence of orthostatic tachycardia in patients was not significantly different from that of healthy controls, those with orthostatic tachycardia were more likely to be earlier in their disease course and had higher rates of steroid use (=.009) and antibiotic exposure (=.007) after Lyme disease. Autonomic symptoms are common in PTLD. The 10-minute active stand test identified a subgroup of patients with orthostatic tachycardia that associated with distinct clinical features of Lyme disease.

: Interleukin-1 (IL-1) inhibitors are approved for the treatment of various inflammatory diseases associated with immune system abnormalities. However, large-scale real-world studies to assess their security are still limited. Therefore, a pharmacovigilance study was conducted based on the data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). : Adverse events (AEs) linked to IL-1 inhibitors were analyzed using the FAERS database from Q1 2004 to Q3 2024. Risk signals were identified through disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). : Among 17,670 AE reports where an IL-1 inhibitor was the "primary suspected" drug, 27 significant system organ classes (SOCs) were identified. Notable signals included infections and infestations (ROR: 2.31, 95% CI: 2.25-2.37) and congenital, familial, and genetic disorders (ROR: 2.26, 95% CI: 2.05-2.48). At the preferred term (PT) level, 263 significant AE signals were detected, such as pyrexia (ROR: 5.27, 95% CI: 5.03-5.53), nasopharyngitis (ROR: 2.31, 95% CI: 2.10-2.54), and injection site erythema (ROR: 6.09, 95% CI: 5.67-6.55). Importantly, we also identified less common or previously unreported AEs, including cardiac disorders (e.g., postural orthostatic tachycardia syndrome with anakinra; pulmonary valve incompetence with rilonacept) and endocrine disorders (e.g., secondary adrenocortical insufficiency with canakinumab). Furthermore, 36.33% of cases emerged after more than 360 days of treatment with IL-1 inhibitors. : This study revealed real-world safety data on IL-1 inhibitors, providing important insights to enhance the clinical use of IL-1 inhibitors and minimize potential AEs.

Postural orthostatic tachycardia syndrome (POTS) and other forms of autonomic dysfunction are increasingly recognized in patients with histories of physical or psychological trauma. 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. However, the relationship between sexual abuse and subsequent autonomic dysfunction remains unclear. We present a series of patients referred to cardiology for suspected POTS, highlighting clinical features, potential mechanisms, and treatment considerations. These findings emphasize the need for trauma-informed evaluation to improve patient care and guide future research.

: Colonoscopy, a common outpatient procedure requiring bowel preparation, can lead to dehydration and electrolyte disturbances. Sedation, while improving patient comfort, may exacerbate these effects and contribute to orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS). This study aimed to determine the prevalence of OH and POTS following sedated colonoscopy and to identify associated risk factors. : This prospective observational study included 76 adult patients (ASA I-III) who underwent colonoscopy with fentanyl-propofol sedation between August and November 2024. Blood pressure, heart rate, and orthostatic intolerance (OI) symptoms were assessed before and after mobilization. OH was defined as a systolic blood pressure decrease ≥20 mmHg or diastolic decrease ≥10 mmHg upon standing. POTS was defined as a heart rate increase ≥30 bpm or an absolute heart rate ≥ 120 bpm. Statistical analyses were performed using SPSS 29.0. : Post-procedural OH and/or POTS occurred in 18 patients (23.7%), and 14 patients (18.4%) reported OI symptoms such as dizziness, nausea, or blurred vision. Symptomatic patients were significantly younger than asymptomatic patients (42.7 ± 15.4 vs. 54 ± 13.9 years, = 0.009), and symptoms were more frequent among females ( = 0.046). Preoperative diastolic blood pressure was significantly higher in patients who developed OH ( = 0.022), while other hemodynamic and demographic variables showed no significant associations. : Orthostatic hypotension and postural tachycardia are relatively common after sedated colonoscopy. Younger age and female sex were identified as independent risk factors for OI symptoms, suggesting a possible role of autonomic variability. Routine post-procedure monitoring and assisted mobilization before discharge may improve patient safety and recovery outcomes.

Postural orthostatic tachycardia syndrome (POTS) is defined as the presence of chronic symptoms of orthostatic intolerance accompanied by an increase in heart rate greater than 30 beats per minute within 10 min of assuming an upright posture in the absences of orthostatic hypotension. It is a condition which lacks a definitive treatment strategy, with weak evidence and clinical expertise to support the available guidelines from the Heart Rhythm Society in 2015 and the Canadian Cardiovascular Society in 2020. The limited systematic reviews evaluating the treatment for POTS only reported three or fewer trials when many more trials have been published. In this systematic review, we evaluate the evidence for different treatments for POTS from 21 randomized clinical trials with 750 patients that took place between 2000 and 2023. This review summarizes the available evidence from trials on propranolol, midodrine, pyridostigmine and ivabradine as well as less commonly used medications such as desmopressin, melatonin, atomoxetine, modafinil, sertraline and intravenous immunoglobulins. Moreover, the trial evidence for non-pharmacological treatments is described including increase intake of dietary sodium, exercise training, compression and devices. We conclude that many small trials have evaluated different treatments for POTS. Large randomized trials are needed to determine if mainstay treatments beta-blockers, midodrine, and pyridostigmine should be used as first line treatment(s).

Human papillomavirus (HPV) vaccination has the potential to enhance prevention of cervical cancer, especially in countries where screening programmes are currently unaffordable or impractical. Rare adverse events and longer-term benefits of HPV vaccination, such as effects on cancer rates, are difficult to examine in randomised controlled trials (RCTs) and require large data from population-level studies to inform decision-making. We aimed to assess population-level effects of HPV vaccination programmes on HPV-related disease and harms from vaccination. We conducted electronic searches on 11 September 2024 in CENTRAL (Cochrane Library), Ovid MEDLINE and Ovid Embase. We also searched vaccine manufacturer websites and checked reference lists from an index of HPV studies and other relevant systematic reviews. We included studies that assessed the impact of HPV vaccination on the general population. This included population-level studies comparing outcomes before and after the introduction of HPV vaccine. We also included individual-level, non-randomised comparative studies, such as cohort studies, case-control studies, cross-sectional studies and self-controlled case series. We used methods recommended by Cochrane. Two review authors carried out data extraction independently using pretested data extraction forms. We assessed the risk of bias of all included effect estimates using different tools according to study design. We carried out quantitative and qualitative data synthesis separately by outcome and study design. We performed meta-analysis on studies that reported effect estimates adjusted for confounding, with a focus on those receiving HPV vaccination at or before the age of 16 years (the target age group for vaccination). We rated the certainty of the evidence with GRADE. We included 225 studies from 347 records in this review, evaluating over 132 million people. We included 86 cohort studies, four case-control studies, 46 cross-sectional studies, 69 pre-post vaccine introduction studies, five RCT extensions and two self-controlled case series. Thirteen additional studies reported on more than one type of analysis. Of the included studies, 177 reported only on females, 11 only males and 37 a combination of males and females. Risk of bias ranged from overall moderate risk to critical risk. Clinical outcomes There was moderate-certainty evidence from 20 studies that HPV vaccination reduces the incidence of cervical cancer. Five cohort studies including 4,390,243 females reported adjusted estimates showing a reduced risk of cervical cancer following HPV vaccination in the long term (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.25 to 0.56; I = 88%). There was a significant interaction with age at vaccination, with a greater risk reduction in younger people. For those vaccinated at or before 16 years of age, covering 4.54 million person-years, there was an 80% reduced risk of cervical cancer (RR 0.20, 95% CI 0.09 to 0.44; I = 69%). One cohort study, one case-control study, one cross-sectional study and three RCT extension studies all reported no cases of cervical cancer in the HPV vaccine groups. Eight pre-post vaccine introduction studies each reported a reduction in cervical cancer incidence following HPV vaccine introduction but did not provide data in a form that allowed for meta-analysis. There was moderate-certainty evidence from 23 studies that HPV vaccination reduces the incidence of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), including 12 cohort studies. For 1.5 million females vaccinated at or before the age of 16 years in two cohort studies, there was a reduction of CIN3+ incidence of 74% in the long term (RR 0.26, 95% CI 0.12 to 0.56; I = 80%). Three case-control studies, one RCT extension study and three cross-sectional studies also reported a decreased risk of CIN3+ in vaccinated participants. One cross-sectional study reported no difference in the risk of CIN3+. Three pre-post vaccine introduction studies reported a decrease in CIN3+ incidence following HPV vaccine introduction. There was moderate-certainty evidence from 37 studies that HPV vaccination reduces the incidence of CIN2+. In cohort studies with females vaccinated at or before the age of 16 years, a reduction in risk was seen in the medium term (RR 0.59, 95% CI 0.54 to 0.65; 2 cohort studies, 233,468 females; I = 0%) and long term (RR 0.38, 95% CI 0.31 to 0.45; 5 cohort studies, 6,455,176 females; I = 64%). There was moderate-certainty evidence from 47 studies that HPV vaccination reduces the incidence of anogenital warts. From the cohort studies with adjusted estimates, the pooled impact of HPV vaccination on rates of anogenital warts indicated a reduction of 47% in the medium term (RR 0.53, 95% CI 0.37 to 0.77; 4 studies, 6,430,295 females and 313 males; I = 98%) and 53% in the long term (RR 0.47, 95% CI 0.36 to 0.61; 13 studies, 4.5 million person-years plus 5,802,969 females and males; I = 99%). Twenty-three pre-post vaccine introduction studies reported a decrease in anogenital warts incidence following the introduction of HPV vaccine. Six studies reported no difference in anogenital warts incidence. There was only very low-certainty evidence on the effect of HPV vaccination on the incidence of adenocarcinoma in situ (three studies) and vulval cancer (five studies). No studies were identified that reported on community rates of serious adverse events following HPV vaccination. Specific adverse events Across a range of study designs, HPV vaccination was not associated with an increased risk of postural orthostatic tachycardia syndrome, chronic fatigue syndrome/myalgic encephalomyelitis, paralysis, complex regional pain syndrome, premature ovarian failure, infertility or sexual activity (all moderate-certainty evidence). There was evidence that suggests HPV vaccination was not associated with an increased risk of Guillain-Barré syndrome (low-certainty evidence). There are now long-term outcome data from different countries and from different study designs that consistently report a reduction in the development of high-grade CIN and cervical cancer in females vaccinated against HPV in early adolescence. Data show that there is greater benefit to vaccinating younger adolescents prior to becoming sexually active. There is evidence that HPV vaccination does not increase the risk of the most common adverse events reported on social media.

Cardiovascular autonomic disorders (CAD) were described following COVID-19 infection and vaccination, but previous reports were limited in size and follow-up. Here, we aimed to investigate the type and frequency of newly diagnosed and exacerbated CAD following COVID-19 infection or vaccination, and assessed their associated autonomic and non-autonomic complaints, applied treatment, and clinical outcome at last follow-up. Medical records of individuals referred to the Innsbruck Dysautonomia Center between March 2020 and March 2023 were reviewed for new onset of orthostatic intolerance, recurrent syncope, OR exacerbation of previously diagnosed CAD within 6 weeks from a passed COVID-19 infection or vaccination. Following COVID-19 infection (n = 75), 22 (29%) individuals were diagnosed with postural orthostatic tachycardia syndrome (POTS), 12 (16%) with vasovagal syncope (VVS), 1 with delayed and 1 with transient orthostatic hypotension (OH). Following COVID-19 vaccination (n = 26), 11 (42%) POTS, 2 (8%) VVS, and 3 (12%) transient OH cases were newly diagnosed. In half of newly referred individuals (n = 49/101, 49%), the diagnostic workup excluded any CAD. VVS was the most frequently exacerbated CAD (n = 8/19, 42%). Non-pharmacological measures were recommended to all newly diagnosed CAD, with one-third additionally receiving pharmacotherapy. Follow-up was available in 42 (81%) individuals with newly diagnosed CAD, with a symptomatic improvement observed in 26 (62%) cases. A specialized diagnostic workup is pivotal to diagnose or exclude CAD in individuals with new-onset orthostatic intolerance or recurrent syncope following COVID-19 infection or vaccination. A multimodal treatment approach can achieve a symptomatic improvement in a substantial proportion of affected individuals.