Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author

Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants - Case Series and Systematic Review of Reported Cases

Background Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature. Methods We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post-thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding. Results Between October 2010 and October 2014, 6 patients received IV-tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method:.8-21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 ± 7.8 [4-28.3] hours. Conclusions Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy. © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved

Racial Difference in Cerebral Microbleed Burden Among a Patient Population in the Mid-South United States

Background: Although intracerebral hemorrhage (ICH) is more common among African-Americans, data on the burden of cerebral microbleeds (CMBs) among different races is limited. The purpose of this study is to compare the number, associated factors, and topography of CMBs between African-American and Caucasian populations in the Mid-South United States. Methods: Using natural language processing, we extracted all brain MRIs performed during a 2-year period (2012-2013) when the report indicated the presence of CMB. All the extracted MRI studies were evaluated for number and location of CMBs, prior stroke, and deep white matter lesion. Negative binomial regression was used to model for the overdispersed count data. Results: A total 167 patients (mean age was 63 ± 15 years, 49% men, 77% African-American, median CMB count: 8) with 1 or more CMBs on their brain MRI were included in this study. There was no significant difference between the 2 groups in terms of CMB locations (P =.086), but there was a significant difference between African-American and Caucasian patients in terms of number of CMBs (16.5 ± 18 versus 6.5 ± 5.5, P <.001). The prevalence of multiple CMBs (CMBs ≥ 5) was similar among African-Americans and Caucasians (72% versus 55%, P =.062). After adjusting for potential confounders, the African-American race was not independently associated with a higher CMB burden (P =.073). Conclusion: African-American race was not independently associated with a higher rate of CMB burden when compared to Caucasians after adjusting for potential confounders. We also did not observe a significant racial difference regarding the location and prevalence of multiple CMBs (CMBs ≥ 5). © 201

Safety of Intravenous Thrombolysis among Patients Taking Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis

Background and Purpose-There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs). Methods-We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria. Results-After reviewing 13 392 reports and communicating with certain authors of 12 published studies, a total of 52 823 acute ischemic stroke patients from 6 studies were enrolled in the present meta-analysis: DOACs: 366, warfarin: 2133, and 50 324 patients without prior anticoagulation. We detected no additional risk of symptomatic intracerebral hemorrhage following IVT among patients taking DOACs within 48 hours-DOACs-warfarin: NINDS (odds ratio [OR], 0.53 [95% CI, 0.18-1.52]), ECASS-II (OR, 0.77 [95% CI, 0.28-2.16]); DOACs-no-anticoagulation: NINDS (OR, 1.23 [95% CI, 0.46-3.31]), ECASS-II (OR, 0.92 [95% CI, 0.33-2.55]). Similarly, no additional risk was detected with no time limit between last DOAC intake-DOACs warfarin: NINDS (OR, 0.85 [95% CI, 0.49-1.45]), ECASS-II (OR, 1.11 [95% CI, 0.67-1.85]); DOACs-no-anticoagulation: NINDS (OR, 1.17 [95% CI, 0.43-3.15]), ECASS-II (OR, 0.87 [95% CI, 0.33-2.41]). There was no evidence of heterogeneity across included studies (I2=0%). We also provided the details of 123 individual cases with or without reversal agents before IVT. There was no significant increase in the risk of hemorrhagic transformation (OR, 1.48 [95% CI, 0.50-4.38]), symptomatic hemorrhagic transformation (OR, 0.47 [95% CI, 0.09-2.55]), or early mortality (OR, 0.60 [95% CI, 0.11-3.43]) between cohorts who did or did not receive prethrombolysis idarucizumab. Conclusions-The results of our study indicated that prior intake of DOAC appears not to increase the risk of symptomatic intracerebral hemorrhage in selected AIS patients treated with IVT. © 2020 Lippincott Williams and Wilkins. All rights reserved

The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis

© 2017 Taylor & Francis Group, LLC. Traumatic brain injury (TBI) is a major health concern. The purpose of this study is to identify the diagnostic accuracy of ubiquitin C-terminal hydrolase-L1 (UCH-L1)—a protein biomarker—in comparison with CT-scan findings post-TBI. Accordingly, we conducted a systematic review of eligible studies and assessed the risk of bias according to the QUADAS-2 checklist. A total of 13 reports from 10 original studies were included. Based on our analysis, serum UCH-L1 has a high accuracy in predicting CT findings in mild to moderate TBI. Based on the QUADAS-2 checklist, this result has a high risk of bias affecting its applicability. The plasma level of UCH-L1 has moderate accuracy in predicting CT findings when assessed in all GCS levels. This result has a low risk of bias and low concerns regarding applicability. Pooled analysis suggests that the plasma/serum UCH-L1 level has high accuracy in predicting CT findings in a wide range of GCS in patients with TBI. This result has a high risk of bias and high concern about its applicability. The heterogeneity in approaching TBI biomarker interferes with drawing a definitive conclusion. Therefore, although UCH-L1 is a promising blood-based diagnostic biomarker for TBI, but due to differences in reported diagnostic accuracy, further studies are needed to recommend UCH-L1 as an alternative to CT scanning

Cerebral Microbleeds are Associated with Higher Mortality Among Ischemic Stroke Patients

Background: Several studies have shown that cerebral microbleeds (CMBs) increase the risk of long-term stroke-related mortality. The purpose of this study was to determine if the existence and burden of CMBs are a predictor of in-hospital death among patients with acute ischemic stroke (AIS). Methods: We studied consecutive ischemic stroke patients who admitted to our tertiary center over a 2-year period (2013-2014). Patients who underwent thrombolysis were excluded. Baseline characteristics of patients, number and topography of CMBs, white matter lesions, and spontaneous symptomatic hemorrhagic transformation were recorded. Outcome measure in our study was in-hospital death. Results: Out of 1126 consecutive AIS patients evaluated in this study, 772 patients included in the study (mean age 61.9 ± 14.2 years [18-95 years], 51.6% men, and 58.2% African American). CMBs were present on the magnetic resonance imaging (MRI) sequences of 124 (16.1%) patients. The overall rate of in-hospital mortality was 4.1%. The presence or absence of CMBs was not predictive of in-hospital mortality (P =.058). After adjusting for potential confounders, the presence of ≥4 CMBs on T2*-weighted MRI was independently (P =.004) associated with a higher likelihood of in-hospital death (odds ratio: 6.6, 95% confidential interval: 2.50 and 17.46) in multivariable logistic regression analyses. Older age, higher National Institute of Health stroke scale, and history of atrial fibrillation were also associated with greater chance of in-hospital death. Conclusions: The presence or absence of CMBs was not predictive of in-hospital mortality. However, the presence of multiple CMBs was associated with a higher in-hospital mortality rate among AIS patients. © 201

Imputation of missing values for electronic health record laboratory data

Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients’ comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method

Racial Difference in Cerebral Microbleed Burden among Ischemic Stroke Patients

Background and Aims Data on the epidemiology of cerebral microbleeds (CMBs) among patients with ischemic stroke are limited. This study compared the number, associated factors, and topography of CMBs between African American and Caucasian ischemic stroke patients in the Mid-South United States. Method We evaluated consecutive ischemic stroke patients admitted to our tertiary stroke center, University of Tennessee Health Science Center, Memphis, Tennessee, in a two-year period. We analyzed T2*-weighted magnetic resonance images for the number, location, and topography of CMBs, as well as patients' demographic and clinical information. Results Among 760 ischemic stroke patients who were included (mean age was 62.1 ± 13.9 years, 51.4% men), 450 (59.2%) were African American. In comparison with Caucasians, African Americans were about five years younger (P =.000) and had a higher rate of hypertension (80.9% vs. 74.5%, P =.036). Similarly, African Americans had a higher prevalence of diabetes mellitus (P =.001). There was no significant difference between African-Americans and Caucasians in terms of CMBs presence and location. African Americans had a higher number of CMBs in comparison with Caucasians, but the difference was not significant. African Americans were more likely to have CMBs ≥5 (P =.047). Although African American stroke patients had a higher rate of large confluent white matter lesions, there was no significant racial difference regarding the rate and severity of deep white matter lesions. Conclusion We did not observe any differences between African American and Caucasian patients with ischemic stroke patients regarding the presence, number, and location of CMBs. However, our results suggested that the prevalence of multiple CMBs (CMBs ≥5) might be higher among African American stroke patients. © 2017 National Stroke Associatio

Safety of Intravenous Thrombolysis in Chronic Intracranial Hemorrhage: A Five-Year Multicenter Study

Introduction: Although the recently updated U.S. alteplase label removed “history of intracranial hemorrhage (ICH)” as a contraindication, there are very limited data on the safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with chronic ICH. We sought to evaluate IVT safety in AIS patients with a history of ICH. Methods: We analyzed consecutive AIS patients treated with IVT at 3 tertiary stroke centers during a 5-year period. We identified AIS treated with IVT with clinical history and neuroimaging confirmation of prior ICH. The safety measure was symptomatic ICH (sICH) defined according to European Cooperative Acute Stroke Study-III criteria combined with the clinical deterioration of 4 points or higher in the National Institutes of Health Stroke Scale (NIHSS) or death. Results: Of the 1212 AIS patients treated with IVT, 7 (.6%) (mean age 72 ± 11 years, 57% men, median NIHSS: 5 points, interquartile range: 2-8) had a history of ICH (hematoma volume: 1-21 cm3, elapsed time between previous ICH and AIS: 1.5-12 years, 5 located in basal ganglia and 2 in periventricular white matter). Patients with previous ICH did not differ in terms of demographics and admission stroke severity in comparison with the rest. The 2 groups had similar rates of sICH (0% [0/7] versus 3.6%, P =.61) and in-hospital mortality (0% [0/7] versus 6.0%, P =.50). Conclusion: Our study indicates that IVT might be safe among AIS patients with a history of chronic ICH. Further research with a larger sample size is required to confirm our finding and define the shortest time interval between the hemorrhagic and ischemic events that can be associated with the safe administration of IVT. © 2018 National Stroke Associatio