Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

White Matter Hyperintensities on Post-Stroke Balance and Gait Recovery: A Prospective Cohort Study Protocol.

INTRODUCTION: White matter hyperintensities (WMH) are commonly associated with balance and gait disturbances. Little is known whether WMH may affect post-stroke balance and gait recovery. We aim to investigate the association of post-stroke balance and gait recovery with imaging marker of WMH on magnetic resonance imaging (MRI). METHODS: This prospective cohort study will enroll consecutive patients with first-ever ischemic hemisphere stroke, between September 2023 and December 2024. Clinical data will be collected on day 30±3 and at 3-month after stroke onset. WMH on FLAIR are graded according to the modified Fazekas scale. Resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) will be acquired to evaluate functional and structural connectivity. The primary endpoint is balance recovery, defined as a Postural Assessment Scale for Stroke score of 32 or higher at 3-month. The secondary endpoint is gait recovery, assessed using the modified Fugl-Meyer Gait Assessment at 3-month. We will investigate the association of post-stroke balance and gait recovery with WMH severity as well as WMH-related functional and structural connectivity. CONCLUSION: The study may contribute to clarify the effect of WMH on post-stroke balance and gait disorder recovery.

Atrial Fibrillation and Clinical Outcomes of Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis of Adjusted Effect Estimates.

BACKGROUND: The impact of atrial fibrillation (AF) on the clinical outcomes in patients with acute ischemic stroke (AIS) who received endovascular thrombectomy remains unclear. We aimed to perform a meta-analysis of adjusted effect estimates to examine the association between the presence of AF and the clinical outcomes in patients with AIS who received endovascular thrombectomy. METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane database between January 1, 2013 and July 10, 2023. Data were meta-analyzed to compare the outcomes among patients with AIS with and without AF who received endovascular thrombectomy. Our primary outcome was 90-day functional independence defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent independence (90-day modified Rankin Scale score of 0-1), 90-day mortality, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. Eighteen observational studies comprising 16 096 patients with AIS (mean age, 70.1 years; women, 48.2%; 6862 with AF versus 9234 without AF) were included. There were no statistically significant differences for modified Rankin Scale score of 0 to 2 (pooled odds ratio [OR], 1.14 [95% CI, 0.95-1.37]; [95% prediction interval [PI], 0.72-1.80]), mortality (OR, 0.92 [95% CI, 0.79-1.08]; [95% PI, 0.77-1.11]), symptomatic intracranial hemorrhage (OR, 0.97 [95% CI, 0.71-1.32]; [95% PI, 0.43-2.17]), and any intracranial hemorrhage (OR, 1.08 [95% CI, 0.91-1.28]; [95% PI, 0.74-1.58]) among patients with AIS with and without AF. CONCLUSIONS: This meta-analysis detected no significant differences in 90-day functional outcomes, mortality, and intracerebral hemorrhage risk after endovascular thrombectomy in patients with AIS with and without AF. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD 42021293511.

Association between Triglyceride-Glucose Index and Early Neurological Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND: The triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance which might plausibly influence endogenous fibrinolysis and thus early neurological outcomes in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis using recombinant tissue-plasminogen activator. METHODS: We included consecutive AIS patients within 4.5 h of symptom onset undergoing intravenous thrombolysis between January 2015 and June 2022 in this multi-center retrospective observational study. Our primary outcome was early neurological deterioration (END), defined as ≥2 (END2) or ≥ 4 (END4) National Institutes of Health Stroke Scale (NIHSS) score worsening compared to the initial NIHSS score within 24 h of intravenous thrombolysis. Our secondary outcome was early neurological improvement (ENI), defined as a lower NIHSS score at discharge. TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. We evaluated the association of END and ENI with TyG index using a logistic regression model. RESULTS: A total of 676 patients with AIS were evaluated. The median age was 68 (Interquartile range, IQR (60-76) years old), and 432 (63.9%) were males. A total of 89 (13.2%) patients developed END2, 61 (9.0%) patients developed END4, and 492 (72.7%) experienced ENI. In multivariable logistic regression analysis, after adjustment for confounding factors, TyG index was significantly associated with increased risks of END2 (categorical variable, vs. lowest tertile, medium tertile odds ratio [OR] 1.05, 95% confidence interval, CI 0.54-2.02, highest tertile OR 2.94, 95%CI 1.64-5.27, overall p < 0.001) and END4 (categorical variable, vs. lowest tertile, medium tertile OR 1.21, 95%CI 0.54-2.74, highest tertile OR 3.80, 95%CI 1.85-7.79, overall p < 0.001), and a lower probability of ENI (categorical variable, vs. lowest tertile, medium tertile OR 1.00, 95%CI 0.63-1.58, highest tertile OR 0.59, 95%CI 0.38-0.93, overall p = 0.022). CONCLUSIONS: Increasing TyG index was associated with a higher risk of END and a lower probability of ENI in patients with acute ischemic stroke treated with intravenous thrombolysis.

Future COVID-19 Booster Vaccine Refusal in Healthcare Workers after a Massive Breakthrough Infection Wave, a Nationwide Survey-Based Study.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79-1.72, nurse-adjusted OR 1.88, 95%CI 1.24-2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05-2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.

A comparison of low- versus standard-dose bridging alteplase in acute ischemic stroke mechanical thrombectomy using indirect methods.

Background: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. Aims: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. Methods: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT. Primary efficacy outcomes were functional independence and excellent recovery defined as a dichotomized modified Rankin Scale (mRS) 0-2 and 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). Results: We included six RCTs of 2334 AIS patients in this analysis, including one trial using low-dose bridging alteplase (n = 103) and five trials using standard-dose bridging alteplase (n = 1067) against a common comparator (dMT). Indirect comparisons of low- to standard-dose bridging alteplase yielded an odds ratio (OR) of 0.84 (95% CI 0.47-1.50) for 90-day mRS 0-2, 1.18 (95% CI 0.65-2.12) for 90-day mRS 0-1, 1.21 (95% CI 0.44-3.36) for mortality, and 1.11 (95% CI 0.39-3.14) for successful recanalization. There were no significant differences in the odds for sICH (OR 1.05, 95% CI 0.32-3.41) or any ICH (OR 1.71, 95% CI 0.94-3.10) between low- and standard-dose bridging alteplase. Conclusion: Indirect evidence shows that the effects of low- and standard-dose bridging alteplase are similar for key efficacy and safety outcomes. Due to the wide confidence intervals, larger randomized trials comparing low- and standard-dose alteplase bridging therapy are required.

Psychological stress and coping strategies among frontline healthcare workers supporting patients with coronavirus disease 2019: a retrospective study and literature review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak might have a psychological impact on frontline healthcare workers. However, the effectiveness of coping strategies was less reported. OBJECTIVES: We aimed to investigate the sources of stress and coping strategies among frontline healthcare workers fighting against COVID-19. We also performed a literature review regarding the effects of coping methods on psychological health in this population. METHODS: We included frontline healthcare workers who completed an online survey using self-made psychological stress questionnaires in a cross-sectional study. We evaluated the association between potential factors and high-stressed status using a logistic regression model. We performed the principal component analysis with varimax rotation for factor analysis. We also performed a systematic review of published randomized controlled studies that reported the effects of coping methods on psychological health in COVID-19 healthcare workers. RESULTS: We included 107 [32 (29-36) years] respondents in the final analysis, with a response rate of 80.5%. A total of 41 (38.3%) respondents were high-stressed. Compared with the low-stressed respondents, those with high-stress were less likely to be male (46.3% versus 72.7%, p = 0.006), nurses (36.6% versus 80.3%, p < 0.001), and more likely to have higher professional titles (p = 0.008). The sources of high-stress in frontline healthcare workers were categorized into 'work factor', 'personal factor', and 'role factor'. A narrative synthesis of the randomized controlled studies revealed that most of the coping methods could improve the psychological stress in healthcare workers during the COVID-19 pandemic. CONCLUSION: Our findings suggest that some frontline healthcare workers experienced psychological stress during the early pandemic. Effective coping strategies are required to help relieve the stress in this population.

Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke.

Background: Factors for the utilization of intravenous thrombolysis with a low-dose of alteplase (0.6mg/kg) and whether the low-dose of alteplase could reduce the risk of intracerebral bleeding in acute ischemic stroke (AIS) remains uncertain. Aims: We aimed to investigate determinants for the utilization of intravenous thrombolysis with a low-dose of alteplase. We further assessed the association between the low-dose of alteplase and the intracerebral bleeding risk in AIS patients. Method: We included AIS patients who received intravenous thrombolysis using alteplase in this multicenter retrospective observational study. We investigated the association between baseline characteristics and the utilization of a low-dose of alteplase to identify determinants. We assessed the association of the low-dose of alteplase with the risk of symptomatic intracranial hemorrhage (sICH) using a multivariable logistic regression model. We further compared the rate of sICH and any ICH in patients in the low-dose group to those in the standard-dose group, using propensity score-matching data. Results: A total of 506 AIS patients were included in this study. The mean age was 67 (interquartile range [IQR] 59-75), and 178 (35.2%) were women. A total of 96 patients were treated with the low-dose. Age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 -1.04, p = 0.042), having a previous ischemic stroke (adjusted OR 2.01, 95%CI 1.11 - 3.64 p = 0.021) and increasing baseline systolic blood pressure (adjusted OR 1.12, 95%CI 1.00 - 1.26, p = 0.049) were determinants for the utilization of the low-dose. Multivariable logistic regression analysis showed that the low-dose was significantly associated with a reduced risk of sICH (adjusted OR 0.13, 95%CI 0.03 - 0.62, p = 0.01). Propensity score analysis showed that the rate of sICH was significantly lower in the low-dose group compared to standard-dose group (2 [2.3%] vs 10 [11.4%], p = 0.032). There was no significant difference in the rate of any ICH between two groups (14 [15.9%] vs 18 [20.5%], p = 0.434). Conclusions: Patients with increasing age, a higher baseline systolic blood pressure, and previous ischemic stroke were at a higher odd of receiving a low-dose of alteplase. The low-dose was associated with a lower risk of developing symptomatic intracranial hemorrhage.

Association Between Previous Stroke and Severe COVID-19: A Retrospective Cohort Study and an Overall Review of Meta-Analysis.

Objective: The objective of this study was to investigate the association between previous stroke and the risk of severe coronavirus disease 2019 (COVID-19). Methods: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in a retrospective study. We evaluated the unadjusted and adjusted associations between previous stroke and severe COVID-19, using a Cox regression model. We conducted an overall review of systematic review and meta-analysis to investigate the relationship of previous stroke with the unfavorable COVID-19 outcomes. Results: The rate of severe COVID-19 in patients with previous stroke was 28.37 per 1,000 patient days (95% confidence interval [CI]: 10.65-75.59), compared to 3.94 per 1,000 patient days (95% CI: 2.66-5.82) in those without previous stroke (p < 0.001). Previous stroke was significantly associated with severe COVID-19 using a Cox regression model (unadjusted [hazard ratio, HR]: 6.98, 95% CI: 2.42-20.16, p < 0.001; adjusted HR [per additional 10 years]: 4.62, 95% CI: 1.52-14.04, p = 0.007). An overall review of systematic review and meta-analysis showed that previous stroke was significantly associated with severe COVID-19, mortality, need for intensive care unit admission, use of mechanical ventilation, and an unfavorable composite outcome. Conclusion: Previous stroke seems to influence the course of COVID-19 infection; such patients are at high risk of severe COVID-19 and might benefit from early hospital treatment measures and preventive strategies.

Should patients with epilepsy be vaccinated against coronavirus disease 2019? A systematic review and meta-analysis.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccination coverage, willingness, and safety profiles in patients with epilepsy remain poorly understood. We aimed to summarize the available evidence of COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. METHODS: We performed a literature search in the Pubmed, EMBASE, and Cochrane Central Register database between 1 January 2020 and 30 April 2022. We included eligible studies that provided information on the COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. We investigated the association between baseline characteristics of patients with epilepsy and unvaccination status using a fixed-effect model. We calculated the pooled overall willingness to be vaccinated against COVID-19. We systematically reviewed the safety profiles after COVID-19 vaccination in patients with epilepsy. RESULTS: Ten eligible observational studies and two case reports yielded 2589 participants with epilepsy or their caregivers. Among 2145 participants that provided the information of vaccination status, 1508 (70.3%) patients with epilepsy were not administered COVID-19 vaccine, and 58% (95%CI 40-75%) of respondents were willing to be vaccinated against COVID-19. Seizure status (active versus inactive, OR 1.84 95%CI 1.41-2.39, I2 = 0%) rather than seizure type (focal versus non-focal, OR 1.22 95%CI 0.94-1.58, I2 = 0%) was associated with COVID-19 unvaccination status. Vaccines were well-tolerated; epilepsy-related problems such as increase in seizure frequency and status epilepticus after COVID-19 vaccination were uncommon. CONCLUSIONS: Our findings suggest a low COVID-19 vaccination coverage and willingness in patients with epilepsy. Vaccination against COVID-19 appears to be well-tolerated and safe in patients with epilepsy, supporting a positive outlook toward vaccination in this population.

Clinical characteristics of fever clinic visits during the coronavirus disease 2019 pandemic: a retrospective case-control study.

Background: Little is known about the change in characteristics of fever-clinic visits during the coronavirus disease 2019 (COVID-19) pandemic. We sought to examine the changes in the volume, characteristics, and outcomes of patients presenting at a fever clinic duringclinic during the first-level response to COVID-19. Methods: We conducted a single tertiary-center retrospective case-control study. We included consecutive patients aged 14 years or older who visited the fever clinic of a tertiary hospital during the period of the first-level response to the COVID-19 pandemic in Fuzhou, China (from 24 January to 26 February 2020). We also analyzed the data of patients in the same period of 2019 as a control. We compared a number of outcome measures, including the fever clinic volumes, consultation length, proportion of patients with pneumonia, hospital admission rate, and in-hospital mortality, using the fever-clinic visit data during the two periods. Results: We included 1,013 participants [median age: 35; interquartile range (IQR): 27-50, 48.7% male] in this retrospective study, including 707 in 2020 and 306 in 2019. The median daily number of participants who presented at the fever clinic in 2020 was significantly higher than that in 2019 [18 (IQR: 15-22) vs. 13 (IQR: 8-17), P=0.001]. Participants in 2020 had a longer consultation length than those in 2019 [127 (IQR: 51-204) vs. 20 (IQR: 1-60) min, P<0.001]. Participants in 2020 were also more likely to be diagnosed with acute pneumonia than those in 2019 [168 (23.8%) vs. 40 (13.1%), P<0.001]. The hospital admission rate in 2020 was higher than in 2019 [73 (10.3%) vs. 13 (4.2%), P=0.001]. No significant difference was found in terms of the in-hospital mortality of participants in 2020 and 2019 [8 (1.1%) vs. 0, P=0.114]. Conclusions: Our findings suggest a higher visits volume, proportion of acute pneumonia, and hospital admission rate among patients presenting at fever clinic during the COVID-19 pandemic. Improved measures need to be implemented.

Intravenous thrombolysis prior to endovascular treatment for acute ischemic stroke: a meta-analysis.

OBJECTIVES: Whether intravenous thrombolysis provides additional benefits before direct endovascular treatment (dEVT) in acute ischemic stroke remains unclear. We aimed to compare the functional and safety outcomes of dEVT to endovascular treatment with bridging using intravenous thrombolysis (BT) in acute ischemic stroke. METHODS: This meta-analysis included currently available eligible randomized clinical trials (RCTs) by searching in the PubMed, EMBASE, Cochrane Central Register, and the International Stroke Conference and European Stroke Organisation Conference posted abstracts. RESULTS: The six included RCTs yielded 2334 participants (mean age, 69.8 years [SD, 11.4]; women, 44.3%; 1164 in dEVT group and 1170 in BT group). We found not significantly different 90-day functional outcomes of modified Rankin scale (mRS 0 - 2, odds ratio [OR] 0.93, 95%CI 0.79 - 1.09; mRS 0 - 1, OR 0.99, 95%CI 0.82 - 1.18), mortality (OR 1.08, 95%CI 0.86 - 1.35), and symptomatic intracranial hemorrhage (OR 0.72, 95%CI 0.49 - 1.07) for patients in dEVT and BT group. Patients treated with dEVT were less likely to experience successful recanalization (OR 0.72, 95%CI 0.57 - 0.92, p = 0.009) and any intracranial hemorrhage (OR 0.81, 95%CI 0.68 - 0.97, p = 0.02). There were no significant differences regarding procedural complications between the two groups. CONCLUSION: This meta-analysis showed no significant differences in 90-day functional outcomes or mortality between dEVT and BT, but a lower possibility of successful recanalization and intracranial hemorrhage for dEVT.

The Effect of Cerebellar Repetitive Transcranial Magnetic Stimulation on Dysphagia due to Posterior Circulation Stroke, a Randomized Controlled Trial Protocol.

INTRODUCTION: Cerebellum might be active during the task of swallowing. Little is known whether cerebellar repetitive transcranial magnetic stimulation (rTMS) could improve post-stroke dysphagia (PSD) due to occlusion in the posterior circulation. This paper describes the rationale and design of a randomized controlled trial that aims to determine the effect of cerebellar rTMS on dysphagia due to posterior circulation stroke. METHODS AND ANALYSIS: Thirty patients with PSD due to occlusion in the posterior circulation will be randomly divided to receive real (n = 20) or sham (n = 10) cerebellar rTMS. Patients in the real rTMS group will receive 250 pulses rTMS at a low intensity with 10 Hz frequency for 10 days (five consecutive days per week). The severity of dysphagia will be assessed with videofluoroscopic swallowing study (VFSS) using the Rosenbek penetration aspiration scale (PAS), the pharyngeal constriction ratio (PCR), and the dysphagia outcome and severity scale (DOSS) before and immediately after the last session and then again after 1 and 3 months. The functional magnetic resonance imaging (fMRI) will be assessed before and after the last session and then again after 1 month and 3 months. The primary outcome is the improvement of swallowing function determined by PAS, PCR, and DOSS. The secondary outcomes include changes in brain connectivity network detected using fMRI. DISCUSSION: This study will determine whether cerebellar rTMS improves dysphagia due to posterior circulation stroke in Chinese patients. Our findings will contribute to a new approach for swallowing function recovery after posterior circulation stroke.

Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis.

Objective: The aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA). Methods: We retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT. Results: Among 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22-3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756-0.866 vs. 0.784, 95% CI 0.723-0.846, P = 0.0004). Conclusion: The total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Intravenous Thrombolysis Before Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis.

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta-analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90-day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta-analysis of randomized controlled trial and observational data revealed similar 90-day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90-1.19), mortality (OR, 1.03; 95% CI, 0.78-1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76-1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51-0.91; P=0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61-0.84; P<0.001). Conclusions In this meta-analysis of patients with acute ischemic stroke, we found no significant differences in 90-day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: 42021234664.

The predictive value of serum level of cystatin C for COVID-19 severity.

To investigate the potential prognostic value of Serum cystatin C (sCys C) in patients with COVID-19 and determine the association of sCys C with severe COVID-19 illness. We performed a retrospective review of medical records of 162 (61.7 ± 13.5 years) patients with COVID-19. We assessed the predictive accuracy of sCys C for COVID-19 severity by the receiver operating characteristic (ROC) curve analysis. The participants were divided into two groups based on the sCys C cut-off value. We evaluated the association between high sCys C level and the development of severe COVID-19 disease, using a COX proportional hazards regression model. The area under the ROC curve was 0.708 (95% CI 0.594-0.822), the cut-off value was 1.245 (mg/L), and the sensitivity and specificity was 79.1% and 60.7%, respectively. A multivariable Cox analysis showed that a higher level of sCys C (adjusted HR 2.78 95% CI 1.25-6.18, p = 0.012) was significantly associated with an increased risk of developing a severe COVID-19 illness. Patients with a higher sCys C level have an increased risk of severe COVID-19 disease. Our findings suggest that early assessing sCys C could help to identify potential severe COVID-19 patients.

Does pre-existent physical inactivity have a role in the severity of COVID-19?

BACKGROUND AND AIMS: Physical inactivity is considered an important lifestyle factor for overweight and cardiovascular disease. We aimed to investigate the association between pre-existent physical inactivity and the risk of severe coronavirus disease 2019 (COVID-19). METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 who were admitted between 15 February and 14 March 2020 in this retrospective study. We evaluated the association between pre-existent physical inactivity and severe COVID-19 using a logistic regression model. RESULTS: Of 164 eligible patients with COVID-19, 103 (62.8%) were reported to be physically inactive. Univariable logistic regression analysis showed that physical inactivity was associated with an increased risk of severe COVID-19 [unadjusted odds ratio (OR) 6.53, 95% confidence interval (CI) 1.88-22.62]. In the multivariable regression analysis, physical inactivity remained significantly associated with an increased risk of severe COVID-19 (adjusted OR 4.12, 95% CI 1.12-15.14) after adjustment for age, sex, stroke, and overweight. CONCLUSION: Our data showed that pre-existent physical inactivity was associated with an increased risk of experiencing severe COVID-19. Our findings indicate that people should be encouraged to keep physically active to be at a lower risk of experiencing a severe illness when COVID-19 infection seems unpredicted.The reviews of this paper are available via the supplemental material section.