BACKGROUND: Pyridostigmine is hypothesized to improve neurogenic orthostatic hypotension (nOH) symptoms without causing or exacerbating supine hypertension. The objective of this review was to evaluate the safety and efficacy of pyridostigmine for management of nOH.
METHODS: A literature search of PubMed, Embase, and CENTRAL was performed in December 2023 for prospective trials with a placebo or active comparator.
RESULTS: Four randomized and two non-randomized studies were reviewed. Three studies utilizing a single dose, crossover design found significant differences of orthostatics using adjunctive pyridostigmine. Two studies assessing longer-term endpoints demonstrated conflicting efficacy of pyridostigmine with one trial finding significant improvement in orthostatics and symptoms after three months of therapy. Use of pyridostigmine did not lead to supine hypertension with most adverse effects being cholinergic.
CONCLUSIONS: Pyridostigmine may be considered as an adjunctive medication in individuals with nOH refractory to standard treatment options as it carries a favorable safety profile with low risk for supine hypertension.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient\'s performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

BACKGROUND: With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement, isolation, space radiation, and altered bacterial virulence. Current limited data suggests additional health threats compared to Earth.
METHODS: We systematically reviewed PubMed, CENTRAL, Web of Science, EMBASE and Cochrane databases for prospective studies on spaceflight and cardiovascular outcomes. Search terms combined cardiovascular disease topics with spaceflight concepts. No date or language restrictions were imposed.
RESULTS: 35 studies representing 2696 space travelers met inclusion criteria. Studies were grouped into spaceflight associations with: atherosclerosis, mortality, cardiac function, orthostatic intolerance, and arrhythmias. Atherosclerosis evidence was limited, with animal studies linking space radiation to endothelial damage, oxidative stress, and inflammation. However, human data showed no significantly increased atherosclerotic disease in astronauts. Mortality studies demonstrated lower cardiovascular mortality in astronauts compared to the general population however there was conflicting data. Cardiac function studies revealed physiologic ventricular atrophy, increased arterial stiffness, and altered blood flow distribution attributed to microgravity exposure. Effects appeared transient and reversible post-flight. Orthostatic intolerance studies found astronauts experienced altered heart rate variability, baroreflex response, and blood pressure changes post-flight. Arrhythmia studies showed increased ventricular ectopy during spaceflight, but limited data on long term flights.
CONCLUSIONS: Environmental space hazards impact the cardiovascular system through multiple mechanisms. Microgravity causes cardiac atrophy and orthostatic intolerance while space radiation may potentially accelerate atherosclerosis. Further research is needed, especially regarding long-term spaceflights.

The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.

Orthostatic intolerance (OI)-type events following hip and knee arthroplasty increase the risk of falls, hospital length of stay, and health-care costs. There is a limited understanding of the incidence of and risk factors for OI-type events in patients during the acute hospital stay. Our aim was to systematically review the incidence of and risk factors for OI-type events during the acute hospital stay following hip and knee arthroplasty.
A systematic review and meta-analysis of studies that investigated the incidence of and risk factors for OI-type events was undertaken. A comprehensive search was performed in MEDLINE, Embase, and CINAHL from their inception to October 2021. The methodological quality of identified studies was assessed using the modified version of the Quality in Prognosis Studies (QUIPS) tool.
Twenty-one studies (14,055 patients) were included. The incidence was 2% to 52% for an OI event, 1% to 46% for orthostatic hypotension, and 0% to 18% for syncope/vasovagal events. Two studies reported female sex, high peak pain levels (>5 out of 10) during mobilization, postoperative use of gabapentin, and the absence of postoperative intravenous dexamethasone as risk factors. There was no consensus on the definition and assessment of an OI-type event.
OI-type events are common during the acute hospital stay following hip and knee arthroplasty, and 4 risk factors have been reported for OI-type events. High-quality prospective cohort studies are required to systematically and reliably determine the incidence of and risk factors for OI-type events.
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and quality of life. It is currently poorly understood with no approved licensed treatments. The aim of this systematic review was to contextualize the symptom burden of POTS, and review factors associated with this burden that may guide future treatments. The specific questions were (1) How does symptom burden in POTS compare to the burden in other long term conditions (LTCs), (2) Which factors are associated with POTS symptom burden, and (3) Which interventions show promise in reducing symptom burden in POTS.
Electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, APA PsycArticles, OpenGrey) were searched from inception to January 2022 for observational studies reporting on the association between any biological, psychological or social factors and symptom burden, and randomized controlled trials reporting on interventions for symptom burden in adults with POTS. Two reviewers independently conducted eligibility screening, data extraction and quality assessment. A narrative synthesis was undertaken.
5159 entries were screened for eligibility. Twenty-nine studies were included (1372 participants with POTS of a total sample size of 2314, 17 High-, 12 Medium-quality), seventeen were observational and twelve were randomized controlled experimental and intervention trials. Overall methodological quality of the evidence was medium-high but heterogeneity was high and sample sizes modest, allowing moderately robust conclusions. Orthostatic symptom burden was higher in POTS than other LTCs. Serum activity against adrenergic α1 receptors, physical functioning, depression, catastrophizing, prolonged cognitive stress testing and anxiety were significantly associated with symptom burden in medium-high quality studies. Preliminary medium-high quality evidence from predominantly proof-of-concept (n = 11) studies and one 3-month 2 × 2 factorial design trial suggest that compression garments, propranolol, pyridostigmine, desmopressin, and bisoprolol may hold promise in reducing symptom burden. Directions for future research include investigating associated factors over time, the development of complex interventions which address both biological and psychosocial factors associated with symptom burden, and effectiveness trials of these interventions.
POTS symptom burden is high, particularly in relation to orthostatic intolerance when compared to other long-term conditions (LTCs). Despite this burden, there are no effectiveness randomized controlled trials of treatment to reduce symptoms in POTS. This review provides a starting point to understanding researched biological and psychosocial factors associated with this burden. There was however inconsistency in the measurement of symptom burden, lowering the confidence of cross-study inferences. A coherent definition of POTS symptom range, severity and impact along with a validated and reliable POTS-specific instrument is currently lacking. A standardized questionnaire to assess POTS symptom burden as a core outcome measure will help clarify future research and clinical practice.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, \"crash\" position, and bending foreword. CPM were assessed in laboratory-based studies (N = 28), the community setting (N = 4), both laboratory and community settings (N = 3), and during blood donation (N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

UNASSIGNED: Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome is an underreported pediatric vascular disorder from the group of acrosyndromes. In children, these include paroxysmal acrosyndromes (Raynaud\'s phenomenon and chilblain-like lesions), permanent acrosyndromes (acrocyanosis), and transient acrosyndromes, in which their pathogeneses are associated with virus infections, Epstein-Barr virus, and, more recently, SARS-CoV-2, respectively.
UNASSIGNED: We reported a case of BASCULE syndrome associated with postural orthostatic tachycardia syndrome (POTS) and provided a narrative review of case reports describing the BASCULE syndrome in children. Moreover, we presented the results of a prospective practice survey that we performed in the French medical community.
UNASSIGNED: A 14-years-old boy reported pruritic erythrocyanic lesions on the lower limbs, which occurred whenever he was in a standing position and fully resolved when he laid down. He reported asthenia and cramps. He presented a typical BASCULE syndrome associated with POTS confirmed by a tilt-test. Physical and vascular examinations were within the normal range. We identified 12 case reports, describing 21 pediatric cases since 2016. Most patients were adolescents between 12 and 19 years of age or were newborns. Furthermore, 20% of cases in the literature have presented POTS or orthostatic intolerance. Our survey among 95 French physicians confirmed that BASCULE syndrome is an underdiagnosed and under recognized disease in the general pediatric practice, at least in France. Among these physicians, 65% had already encountered patients with similar symptoms, but only 30% declared that they had knowledge of the BASCULE syndrome.
UNASSIGNED: The under-recognition of the clinical manifestations leads the patients to consult emergency rooms, with multiple unnecessary investigations performed. Therefore, we suggest that the diagnosis of BASCULE syndrome is based on clinical observations, without the need for laboratory tests, to avoid unnecessary health costs. We suggest physicians to perform a tilt-test when POTS is suspected.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at least 6 months accompanied by problems with unrefreshing sleep, exacerbation of symptoms following physical or mental efforts (postexertional malaise [PEM]), and either cognitive reports or physiological evidence of orthostatic intolerance in the form of either orthostatic tachycardia and/or hypocapnia. Although rarely considered to have cardiac dysfunction, ME/CFS patients frequently have reduced stroke volume with a significant inverse relation between cardiac output and PEM severity. Magnetic resonance imaging of ME/CFS patients compared with normal control subjects found significantly reduced stroke, end-systolic, and end-diastolic volumes together with reduced end-diastolic wall mass. Another cardiovascular abnormality is reduced nocturnal blood pressure assessed by 24-hour monitoring. Autonomic dysfunction is also frequently observed with postural orthostatic tachycardia and/or hypocapnia. Two consecutive cardiopulmonary stress tests may provide metabolic data substantiating PEM.

There have been increased reports of orthostatic intolerance post-bariatric surgery. However, the prevalence, pathophysiology and long-term outcomes have not been well described. Therefore, we sought to summarize evidence of orthostatic intolerance after bariatric surgery. We conducted a systematic review using PubMed, Scopus, CINAHL, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant articles from the date of inception until 1st April 2020. Study selection, data extraction and quality assessment of the included studies were performed independently by two reviewers. The findings of the included studies were narratively reported. When feasible, a meta-analysis was done to summarize the relevant results. We included 20 studies (n = 19 843 participants) reporting findings of 12 prospective cohort studies, 5 retrospective cohort studies, 2 cross-sectional studies and one randomized controlled trial. The 5-year cumulative incidence of orthostatic intolerance was 4.2% (one study). Common clinical presentations of orthostatic intolerance were lightheadedness, dizziness, syncope and palpitation. The pooled data suggested improvement in overall cardiac autonomic function (sympathetic and parasympathetic) post-bariatric surgery. In addition, a significant systolic blood pressure drop may reflect a reset of the balance between the sympathetic and parasympathetic nervous systems after weight loss in the pooled analysis. Existing literature on orthostatic intolerance post-bariatric surgeries was limited or of low quality, and larger studies are needed to know the true incidence of orthostatic intolerance post-bariatric surgeries and the pathophysiology. We found one study reporting the 5-years cumulative incidence of orthostatic intolerance post-bariatric surgeries as only 4.2%. This could challenge the idea of increased orthostatic intolerance prevalence post-bariatric surgeries. Registration The review protocol was registered at the International Prospective Register of Systemic Reviews PROSPERO (CRD42020170877).