Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. METHODS: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. RESULTS: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. CONCLUSIONS: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Prevalence and epidemiology of stroke in patients with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). OBJECTIVE: To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients. METHODS: Systematic review and meta-analysis of registry-based and cohort studies. RESULTS: Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3-4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97-3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8-4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2-1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27-3.41) and ICH (RR: 2.31; 95% CI 1.04-5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9-24.7%) for dyslipidaemia, 18.2% (95% CI 5.9-35.3%) for hypertension and 5.4% (95% CI 2.1-10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (ß = - .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0-5) attenuation of the risk of AIS. CONCLUSION: The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.

Waist Circumference and Body Mass Index as Predictors of Disability Progression in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: While obesity has been shown to elevate the risk of developing multiple sclerosis (MS), there is a lack of strong evidence regarding its role in the disability progression and status of MS patients. Methods: This systematic review and meta-analysis aimed to provide comparative estimates of WC and BMI in patients with MS (PwMS) and to investigate potential associations between the waist circumference (WC) and body mass index (BMI) and demographic and specific MS characteristics. Adhering to PRISMA guidelines, a detailed search of the MEDLINE PubMed, Cochrane Library, and Scopus databases was conducted. Results: A total of 16 studies were included. The pooled mean WC and BMI among PwMS was estimated to be 87.27 cm (95%CI [84.07; 90.47]) and 25.73 (95%CI [25.15; 26.31]), respectively. Meta-regression models established a significant bidirectional relationship between WC and the Expanded Disability Scale (EDSS) (p < 0.001) but not between BMI and EDSS (p = 0.45). Sensitivity analyses showed no association between WC and age (p = 0.48) and a tendency between WC and disease duration (p = 0.08). Conclusions: Although WC measurements classify PwMS as normal weight, BMI measurements classify them as overweight. Therefore, WC should complement BMI evaluations in clinical practice. Additionally, our findings highlight the significant association between abdominal fat, as indicated by WC, and disease progression. Considering the heightened risk of cardiovascular comorbidity and mortality among PwMS, we recommend integrating both WC and BMI as standard anthropometric measurements in routine clinical examinations and targeted prevention strategies for PwMS.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience.

BACKGROUND: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. METHODS: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. RESULTS: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. CONCLUSIONS: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.

INTRODUCTION: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM. PATIENTS AND METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). RESULTS: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. DISCUSSION AND CONCLUSION: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

Computed tomography perfusion imaging-guided intravenous thrombolysis in acute minor ischemic stroke.

Background: Over 50% of acute ischemic stroke (AIS) patients present with minor neurological deficits, and optimal treatment is still debated. The randomized PRISMS trial did not show beneficial effects of intravenous thrombolysis (IVT) in unselected patients with minor stroke and non-disabling neurological deficits. Purpose: The study aimed to evaluate if AIS patients with minor stroke may benefit from computed-tomography-perfusion (CTP)-guided IVT. The primary endpoint was good functional outcomes, defined as a modified Rankin Scale score of 0-2 at 90 days. Methods: AIS patients with a NIHSS of ≤5 presenting within 4.5 h underwent multimodal CT-imaging including CTP. CTP mismatch was defined as hypoperfusion on CTP with time-to-peak delay >6 s without corresponding hypoperfusion in cerebral blood volume. IVT decision was left to the attending stroke physicians. Patients with large vessel occlusion (LVO) and absolute contraindications to IVT were excluded. Results: In total, 267 consecutive patients were included [mean age: 72 ± 14 years, 45.3% female patients, 75.3% received IVT, median NIHSS on admission: 3 (IQR 2, 4)]. CTP mismatch was detected in 41.8% of IVT- treated patients (IVT+) and 28.8% of standard treatment patients (IVT-) (p = 0.06). IVT+ had favorable outcomes at 90 days compared to IVT- (p = 0.006), but no interaction with an existing CTP mismatch was detected (ORadj: 1.676; 95% CI: 0.644-4.364). No symptomatic intracranial hemorrhage according to ECASS-III criteria occurred. Conclusion: Although selected AIS patients with minor stroke may benefit from IVT, CTP mismatch does not correlate with functional outcomes. No benefit from CTP mismatch in guiding IVT was detected in patients without LVO presenting with minor neurological deficits.

Periodic Limb Movements during Sleep in Acute Stroke: Prevalence, Severity and Impact on Post-Stroke Recovery.

BACKGROUND: Periodic Limb Movements during Sleep (PLMS) have been described to be frequently present in stroke patients. We aimed to evaluate the prevalence and severity of PLMS in acute stroke patients and clarify the association between PLMS and coexisting Sleep Disordered Breathing (SDB). Additionally, we focused on identifying variables that could independently predict the presence of PLMS in patients with acute stroke. The potential impact of PLMS on stroke outcome at three months was investigated as well. METHODS: In this study, we performed overnight polysomnography on consecutive stroke patients within 72 h from symptom onset. Data regarding clinical and imaging characteristics were prospectively collected. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Epworth-Sleepiness Scale (ESS) were used to evaluate stroke severity on admission, stroke outcome at three months and history of daytime sleepiness, respectively. We documented PLMS and SDB using standard polysomnography criteria. RESULTS: We prospectively assessed 126 patients with acute stroke [109 with ischemic and 17 with hemorrhagic stroke, mean age 60 ± 11 years, 68% men, median NIHSS score on admission: 3 (IQR: 2-7)]. The overall rate of PLMS in our cohort was 76%, and the rate of SDB among patients with PLMS was 83%. PLMS detection rates differed significantly (p-value: <0.001) according to SDB, with PLMS prevalence increasing with greater SDB severity. SDB could independently (OR:4.869, 95% CI: 1.884-12.784, p-value: 0.001) predict the presence of PLMS in the acute stroke phase in multivariable analyses adjusting for potential confounders. Moreover, baseline stroke severity (NIHSS-score increase in per-1 point: OR: 0.819, 95% CI: 0.737-0.895, p-value < 0.001) and PLMS (OR:0.099, 95% CI: 0.009-0.482, p-value = 0.015) were significantly associated with the likelihood of excellent functional outcome (mRS-scores: 0-1) at 3 months. CONCLUSION: The common presence of mostly severe PLMS in patients with acute stroke and their negative effect on stroke outcomes point out the necessity for early PLMS detection and treatment.

mTOR pathway - a potential therapeutic target in stroke.

Stroke is ranked as the second leading cause of death worldwide and a major cause of long-term disability. A potential therapeutic target that could offer favorable outcomes in stroke is the mammalian target of rapamycin (mTOR) pathway. mTOR is a serine/threonine kinase that composes two protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is regulated by other proteins such as the tuberous sclerosis complex. Through a significant number of signaling pathways, the mTOR pathway can modulate the processes of post-ischemic inflammation and autophagy, both of which play an integral part in the pathophysiological cascade of stroke. Promoting or inhibiting such processes under ischemic conditions can lead to apoptosis or instead sustained viability of neurons. The purpose of this review is to examine the pathophysiological role of mTOR in acute ischemic stroke, while highlighting promising neuroprotective agents such as hamartin for therapeutic modulation of this pathway. The therapeutic potential of mTOR is also discussed, with emphasis on implicated molecules and pathway steps that warrant further elucidation in order for their neuroprotective properties to be efficiently tested in future clinical trials.

Links between trauma and psychosis (Review).

The relationship between trauma and psychosis is complex and multifaceted, with evidence suggesting that trauma can be both a risk factor for the development of psychosis and a consequence of psychotic experiences. The present review aimed to provide an overview of the current state of knowledge on the relationship between trauma and psychosis, including historical and conceptual considerations, as well as epidemiological evidence. The potential explanation of the link between trauma and psychosis is provided through available models and similarities in their neurobiological associations. Overall, the research confirms the relationship between trauma and psychosis, and suggests that individuals with a co-occurring history of trauma and psychosis may have increased symptom severity and worse functional outcomes compared with individuals with psychosis alone. Future research should focus on elucidating the underlying causal pathways between trauma exposure and psychosis in order to inform effective treatment approaches aiming to prevent the intensification of psychotic symptoms and processes.

Predictors of functional outcome after symptomatic intracranial hemorrhage complicating intravenous thrombolysis: results from the SITS-ISTR.

BACKGROUND AND PURPOSE: Several risk factors of symptomatic intracerebral hemorrhage (SICH) following intravenous thrombolysis for acute ischaemic stroke have been established. However, potential predictors of good functional outcome post-SICH have been less studied. METHODS: Patient data registered in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) from 2005 to 2021 were used. Acute ischaemic stroke patients who developed post intravenous thrombolysis SICH according to the SITS Monitoring Study definition were analyzed to identify predictors of functional outcomes. RESULTS: A total of 1679 patients with reported SICH were included, out of which only 2.8% achieved good functional outcome (modified Rankin Scale scores of 0-2), whilst 80.9% died at 3 months. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score and 24-h ΔNIHSS score were independently associated with a lower likelihood of achieving both good and excellent functional outcomes at 3 months. Baseline NIHSS and hematoma location (presence of both SICHs, defined as remote and local SICH concurrently; n = 478) were predictors of early mortality within 24 h. Independent predictors of 3-month mortality were age, baseline NIHSS, 24-h ΔNIHSS, admission serum glucose values and hematoma location (both SICHs). Age, baseline NIHSS score, 24-h ΔNIHSS, hyperlipidemia, prior stroke/transient ischaemic attack, antiplatelet treatment, diastolic blood pressure at admission, glucose values on admission and SICH location (both SICHs) were associated with reduced disability at 3 months (≥1-point reduction across all modified Rankin Scale scores). Patients with remote SICH (n = 219) and local SICH (n = 964) had comparable clinical outcomes, both before and after propensity score matching. CONCLUSIONS: Symptomatic intracerebral hemorrhage presents an alarmingly high prevalence of adverse clinical outcomes, with no difference in clinical outcomes between remote and local SICH.

Myasthenia Gravis Exacerbation Following Immunization With the BNT162b2 mRNA COVID-19 Vaccine: Report of a Case and Review of the Literature.

Acute exacerbations of Myasthenia Gravis (MG) may be triggered by infections and certain drugs. No consensus has been reached on vaccines and the risk for developing myasthenic crisis. During the COVID-19 pandemic, MG patients are considered at high risk for severe illness, and vaccination is strongly recommended. We report the case of a 70-year-old woman with MG, diagnosed 2 years earlier, that developed myasthenic crisis 10 days after the second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). The patient had no previous MG exacerbations in her history. Following increase of oral pyridostigmine and prednisone treatment, the patient underwent immunoglobulin and plasma exchange therapy. Due to persisting symptoms, immunotherapy was switched to rituximab, under which a clinical remission was achieved. MG patients infected with SARS-CoV-2 may develop severe acute respiratory distress syndrome and have a higher mortality compared to the general population. In addition, reports of new-onset MG following COVID-19 infection accumulate. By contrast, since the beginning of the vaccination program, only 3 cases of new-onset MG after COVID-19 vaccinations have been published and 2 cases of severe MG exacerbation. Vaccinations in MG patients have always been debated, but most studies confirm their safety. In the era of COVID-19 pandemic, vaccination protects against infection and severe illness, especially in vulnerable populations. The rare occurrence of side effects should not discourage clinicians from recommending COVID-19 vaccination, but close follow-up of MG patients is recommended during the post-vaccination period.

Effects of Melatonin Administration on Post-Stroke Delirium in Patients with Intracerebral Hemorrhage.

Post-stroke delirium (PSD) after intracerebral hemorrhage (ICH) is considered to be even more detrimental compared to that after ischemic stroke. Treatment options for post-ICH PSD remain limited. This study aimed at investigating to what extent prophylactic melatonin administration may have beneficial effects on post-ICH PSD. We performed a mono-centric, non-randomized, non-blinded, prospective cohort study, including 339 consecutive ICH patients admitted to the Stroke Unit (SU) from December 2015 to December 2020. The cohort consisted of ICH patients who underwent standard care (defined as the control group) and ICH patients who additionally received prophylactic melatonin (2 mg per day, at night) within 24 h of ICH onset until the discharge from the SU. The primary endpoint was post-ICH PSD prevalence. The secondary endpoints were: (i) PSD duration and (ii) the duration of SU stay. The PSD prevalence was higher in the melatonin treated cohort compared to the propensity score-matched (PSM) control group. Post-ICH PSD patients receiving melatonin had shorter SU-stay durations, and shorter PSD durations, although not statistically significant. This study shows no efficacy in limiting post-ICH PSD with preventive melatonin administration.

No evidence of oligoclonal bands, intrathecal immunoglobulin synthesis and B cell recruitment in acute ischemic stroke.

BACKGROUND: Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS. METHODS: In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations. RESULTS: Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS. CONCLUSIONS: We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease.

Sleep-Disordered Breathing in Acute Stroke: A Single-Center, Prospective, Longitudinal Study.

BACKGROUND: Sleep-disordered breathing (SDB) is common among acute stroke patients. We sought to investigate the prevalence, severity and type of SDB in consecutive acute stroke patients. Moreover, we aimed to identify independent predictors of SDB in the acute stroke setting and investigate potential associations between SDB and functional outcomes at three months. METHODS: We prospectively studied consecutive acute stroke patients, who underwent overnight polysomnography within 72 h from symptom onset. Demographics, clinical and imaging characteristics were documented. Daytime sleepiness preceding the stroke, stroke severity on admission and functional outcome at three months were evaluated using the Epworth-Sleepiness Scale (ESS), National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), respectively. SDB was documented using standard polysomnography criteria. RESULTS: A total of 130 consecutive acute stroke patients were prospectively evaluated [110 with ischemic stroke and 20 with intracerebral hemorrhage, mean age 60.5 ± 10.9 years, 77% men, median NIHSS score on admission: 3 (IQR: 2-17)]. The rate of SDB detection on polysomnography recordings was 79% (95% CI: 71-86). Three variables were independently associated with the likelihood of SDB detection in multivariable analyses adjusting for potential confounders: age (OR per 10-year-increase: 2.318, 95% CI: 1.327-4.391, p = 0.005), male sex (OR: 7.901, 95% CI: 2.349-30.855, p = 0.001) and abnormal ESS-score (OR: 6.064, 95% CI: 1.560-32.283, p = 0.017). Among patients with SDB, congestive heart failure was independently associated with the likelihood of central apnea detection (OR: 18.295, 95% CI: 4.464-19.105, p < 0.001). Among all patients, increasing NIHSS score on admission (OR: 0.817, 95% CI: 0.737-0.891, p < 0.001) and Apnea-Hypopnea Index (OR: 0.979, 95% CI: 0.962-0.996, p = 0.020) emerged as independent predictors of excellent functional outcome at 3 months (mRS-scores 0-1). CONCLUSION: The high prevalence and severity of SDB in acute stroke patients and its negative impact on functional outcome indicate the importance of polysomnography implementation in everyday clinical practice of acute stroke work-up and management.

Rescue aortic valvuloplasty for severe aortic stenosis is simple and effective in severely hemodynamically compromised patients presenting to centers without on-site heart surgery or TAVI facilities.

Management of high-risk patients with severe aortic stenosis (AS) is a challenging issue. The prognosis of patients with AS presenting with therapy-refractory pulmonary edema (RPE) or cardiogenic shock (CS) remains poor. The purpose of this study was to assess the 30-day mortality of rescue percutaneous balloon aortic valvuloplasty (PBAV) in AS patients presenting with RPE or CS in a community-based hospital without on-site heart surgery. From January 2016 to February 2019, we identified consecutively admitted patients with CS or RPE related to severe AS who underwent emergent PBAV. The primary end point was 30-day mortality. Secondary end points included procedural adverse events according to the Valve Academic Research Consortium (VARC)-2 criteria and predictive factors of the primary end point. We identified 51 patients with either CS (n = 22) or RPE (n = 29). All PBAV procedures were successful with a significant reduction in peak-to-peak gradient (median, [IQR] from 40 [27] mmHg to 15 [20] mmHg, p < 0.001). No procedural deaths occurred, while adverse events included stroke (4%), minor vascular complications (6%), minor (4%) and major bleedings (4%), and no life-threatening bleeding. Overall, 15 deaths (29%) were noted at 30 days after PBAV, while 53% of the surviving patients were successfully bridged to transcatheter aortic valve implantation (TAVI). 30-day mortality was significantly higher in the CS group compared to the RPE (n = 10 (45%) vs n = 5 (7%), p = 0.029), and was significantly associated with the presence of acute kidney injury (OR 9.09, 95% CI 2.13-38.77, p = 0.003) and elevated pulmonary artery systolic pressure (OR 1.06, 95% CI 1.0-1.12, p = 0.047). Rescue PBAV in patients with severe AS presenting with RPE or CS is a feasible and effective therapeutic option, even in a community-based hospital without on-site heart surgery. Rescue PBAV resulted in 30-day survival of more than 70%, with more than half of the surviving patients having been successfully bridged to TAVI.

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.