From A to E: Uniting vitamins against stroke risk-A systematic review and network meta-analysis.

BACKGROUND AND AIM: Stroke represents a significant public health challenge, necessitating the exploration of preventive measures. This network meta-analysis aimed to assess the efficacy of different vitamin treatments compared to a placebo in preventing stroke. METHODS: A systematic electronic search in databases including PubMed, EmBASE, Web of Science, clinicaltrials.gov, and Google Scholar until 31 May 2023 was conducted, to identify published studies investigating the association between vitamin intake and the risk of stroke. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using a frequentist network meta-analysis. Furthermore, we ranked vitamins based on p-scores, facilitating a comparative assessment of their effectiveness in preventing stroke. RESULTS: A total of 56 studies, including 17 randomized controlled trials (RCTs) and 39 cohort studies were analyzed. Direct estimates obtained from network meta-analysis, we found that vitamin A (RR: .81 [.72-.91]), vitamin B-complex (RR: .85 [.74-.97]), vitamin B6 (RR: 79 [.68-.92]), folate (RR: .86 [.75-.97]), vitamin C (RR: .77 [.70-.85]) and vitamin D (RR: .73 [.64-.83]) were significantly associated with a decreased stroke risk. However, no significant association was observed for vitamin B2, vitamin B12, and vitamin E. Subsequent to network meta-analysis, vitamins were ranked in decreasing order of their efficacy in stroke prevention based on p-score, with vitamin D (p-score = .91), vitamin C (p-score = .79), vitamin B6 (p-score = .70), vitamin A (p-score = .65), vitamin B-complex (p-score = .53), folate (p-score = .49), vitamin B2 (p-score = .39), vitamin E (p-score = .28), vitamin B12 (.13) and placebo (.10). CONCLUSION: Our study has established noteworthy connections between vitamin A, vitamin B-complex, vitamin B6, folate, vitamin C, and vitamin D in the realm of stroke prevention. These findings add substantial weight to the accumulating evidence supporting the potential advantages of vitamin interventions in mitigating the risk of stroke. However, to solidify and validate these observations, additional research is imperative. Well-designed clinical trials or cohort studies are needed to further explore these associations and formulate clear guidelines for incorporating vitamin supplementation into effective stroke prevention strategies.

Decompressive surgery in cerebral venous thrombosis: A systematic review and meta-analysis.

OBJECTIVE: The efficacy of decompressive surgery (DS) in cerebral venous thrombosis (CVT) patients has been reported in several case reports and case series. We aimed at determining the association of DS compared with medical management and timing of surgery with functional outcome and mortality. We also aimed at determining the prevalence of DS in CVT patients. METHODS: The literature search was conducted till 7 November 2022 in PubMed, Google Scholar, EMBASE and Cochrane Library databases. Risk of bias was examined using Joanna Briggs Institute scale for case series and case reports. Association of DS compared with medical management and timing of surgery with functional outcome and mortality was determined using odds ratio (OR) and 95% confidence interval (CI). Pooled prevalence of DS in CVT patients with 95%CI was calculated. Heterogeneity was explored using outlier, meta-regression, sensitivity and subgroup analyses. RESULTS: Fifty-one studies consisting of 483 CVT cases with DS were included. The OR of poor outcome with surgery was 0.03; (95%CI: 0.00-0.22) and of mortality with surgery was 0.25; (95%CI: 0.02-2.60) versus that with medical management. Surgery done ≤48 h of admission was significantly associated with less mortality (OR: 0.26; 95%CI: 0.10-0.69). Pooled prevalence of DS in CVT was 12% (95%CI: 8%-17%; I2  = 91%). Revised pooled prevalence after removing outliers was 10% (95%CI: 7%-13%; I2  = 73%). CONCLUSIONS: Surgery ≤48 h of admission might decrease mortality in CVT patients and may result in improved functional outcome. Further prospective studies with appropriate control arms are required to confirm its efficacy over medical management.

Association of modifiable risk factors with ischaemic stroke subtypes in Asian versus Caucasian populations: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke (IS) is associated with various modifiable risk factors but the association of these risk factors based on TOAST classification, which characterises IS into five subtypes: large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic disease (CE), other determined aetiology (ODE) and undetermined aetiology (UDE), is unknown. We aimed to summarise the published evidence for the association of modifiable risk factors with IS subtypes based on TOAST classification, specifically focussing on the Asian versus Caucasian population. METHOD: A comprehensive search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from 01st January 1950 to 10th April 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratio (OR) with 95% confidence interval (CIs) along with random-effect models was used to calculate summary estimates. RESULTS: In our meta-analysis, 32 studies with a total of 23,404 IS (14,364 in Asian vs. 9040 in Caucasian population), 7121 LAA (5219 in Asian vs. 1902 in Caucasian), 5532 SVO (3604 in Asian vs. 1928 in Caucasian), 3498 CE (1634 in Asian vs. 1864 in Caucasian), 1131 ODE (546 in Asian vs. 585 in Caucasian) and 4519 UDE (2076 in Asian vs. 2443 in Caucasian) were included. Our findings suggest a significant association between LAA and hypertension (OR = 1.07, 95% CI = 1.02-1.12), smoking (OR = 1.11, 95% CI = 1.04-1.17), dyslipidemia (OR = 1.13, 95% CI = 1.06-1.21), diabetes mellitus (OR = 1.18, 95% CI = 1.11-1.25) and atrial fibrillation (OR = 0.55, 95% CI = 0.40-0.75). Significantly strong association of hypertension, smoking, dyslipidemia, diabetes mellitus and atrial fibrillation was observed with SVO and CE stroke subtypes. Subgroup analysis based on ethnicity revealed a significant association for dyslipidemia, diabetes mellitus and atrial fibrillation in LAA for both Asians and Caucasians. Hypertension was significantly associated with SVO and ODE subtypes in both Asians and Caucasians; however, only Asian population showed significant association of hypertension in LAA and CE subtypes. The other risk factors did not show any statistical difference between the ethnic groups for the different stroke subtypes. The majority of the risk factors depicted positive association with LAA and SVO, negative with CE and neutral with ODE and UDE. CONCLUSION: Our findings suggest strong association of smoking, dyslipidemia and diabetes mellitus with LAA and SVO subtypes in the Caucasian population. However, only diabetes mellitus showed significant association with both LAA and SVO subtypes in Asian population as well. Thus, a majority of the traditional modifiable risk factors had a positive association in LAA and SVO, while a negative protective association was observed in CE subtype, among both the Asian and the Caucasian subgroups.

Carotid intima-media thickness and risk of mild cognitive impairment: A systematic review and meta-analysis.

Mild cognitive impairment (MCI) is an early phase of cognitive decline signalling the beginning of severe neurological diseases. Carotid intima-media thickness (cIMT) has shown some correlation with MCI development. This study was conducted to investigate the impact of elevated cIMT on the risk of MCI in adults. A literature search was conducted in PubMed, EMBASE, Cochrane Library, Scopus, Google Scholar and CINAHL databases till 30 July 2021, with keywords: ('Carotid Intima-Media Thickness' OR 'cIMT' OR 'IMT' AND 'Cognitive Impairment' OR 'Cognition' OR 'Cognitive Decline' AND 'Mild Cognitive Impairment' OR 'MCI'). Pooled standardized mean difference (SMD)/odds ratio (OR) and 95% confidence interval (CI) were determined for factor-disease association using either fixed (when I2 <50%) or random effect (when I2 >50%) models. Eight studies involving 1,585 MCI cases and 6,700 normal subjects were included in our meta-analysis which showed no significant association of increased cIMT with the risk of MCI [SMD 1.17, 95% CI -0.09 to 2.42]. However, sensitivity analysis revealed an outlier study significantly affecting the effect size. On omitting the outlier study, the re-evaluated meta-analysis revealed a significant association of cIMT with the risk of MCI [SMD 0.52, 95% CI 0.26 to 0.78]. This significant association was also observed during subgroup analysis in Caucasian population [SMD 0.65, 95% CI 0.13 to 1.18] but not in Asian population [SMD 0.39, 95% CI -0.01 to 0.79]. Elevated cIMT poses a potential risk for MCI. However, more population-based studies are required to corroborate these findings.

Efficacy of various treatment modalities for nCOV-2019: A systematic review and meta-analysis.

BACKGROUND: Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients. METHODS: A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I2  < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2. RESULTS: Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events. CONCLUSION: Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.

CIMT as a risk factor for stroke subtype: A systematic review.

INTRODUCTION: An increase in the common carotid artery intima-media thickness (CCA-IMT) is generally considered an early marker of atherosclerosis and is a well-established predictor of cardiovascular disease (CVD). An association between changes in CCA-IMT and risk of stroke has been reported but has conflicting findings. OBJECTIVE: The present meta-analysis was aimed to clarify the association between CCA-IMT with the risk of stroke and its subtype by estimating pooled analysis of published literature. METHODS: Comprehensive search for all published articles was performed in electronic databases including PubMed, Embase, Cochrane Library, Trip Databases, Worldwide Science, CINAHL and Google Scholar from 01 January 1950 to 30 April 2020. RESULTS: In our meta-analysis, a total of 19 studies, of which sixteen studies involving 3475 ischaemic stroke (IS) cases and 11 826 controls; six studies with 902 large vessel disease (LVD) and 548 small vessel disease (SVD) of IS subtypes; five studies with 228 intracerebral haemorrhage (ICH) and 1032 IS cases, were included. Our findings suggest a strong association between increased CCA-IMT with risk of IS as compared to control subjects [SMD = 1.46, 95% CI = 0.90-2.02]. However, there is an increased risk of LVD as compared to the SVD subtype of IS [SMD = 0.36, 95% CI = 0.19-0.52] and more chance of occurrence of IS rather than ICH [SMD = 0.71, 95% CI = 0.28-1.41]. CONCLUSIONS: Carotid intima thickness measurements are found to be associated with the risk of stroke along with its subtypes and may be used as a diagnostic marker for predicting the risk of stroke events.

Cystatin C and Risk of Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

INTRODUCTION: Cystatin C (Cys C) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer's disease. Published studies on the role of Cys C as a biomarker of mild cognitive impairment (MCI) have not been reviewed systematically. OBJECTIVE: Present meta-analysis was performed to elucidate the association between Cys C and risk of MCI. METHODS: A comprehensive search was performed in PubMed, EMBASE, Cochrane Library, Trip databases, Worldwide Science, and Google Scholar from January 1, 1950, to April 30, 2020. Standardized mean difference (SMD) with 95% confidence interval (CI) using fixed or random effect models were used to calculate summary estimates. Quality of evidence was also assessed using the Diagnostic Accuracy Quality Scale (DAQS) and grading quality of evidence and strength of recommendations approach. RESULTS: In our meta-analysis, 12 studies with a total of 2,433 MCI patients and 1,034 controls were included. Our findings suggest a strong association between increased levels of Cys C and risk of MCI as compared to control subjects (SMD = 2.39, 95% CI = 0.22-4.57). Subgroup analysis based on ethnicity, a significant association for the high level of Cys C with the risk of MCI was observed in the Asian population (SMD = 1.63, 95% CI = 0.44-2.82) but not in the Caucasian population (SMD = 2.80, 95% CI = [-0.66]-6.26). CONCLUSION: Cys C was associated with MCI, and it could be considered as a predictor for the risk of cognitive impairment.

Prognostic biomarkers of intracerebral hemorrhage identified using targeted proteomics and machine learning algorithms.

Early prognostication of patient outcomes in intracerebral hemorrhage (ICH) is critical for patient care. We aim to investigate protein biomarkers' role in prognosticating outcomes in ICH patients. We assessed 22 protein biomarkers using targeted proteomics in serum samples obtained from the ICH patient dataset (N = 150). We defined poor outcomes as modified Rankin scale score of 3-6. We incorporated clinical variables and protein biomarkers in regression models and random forest-based machine learning algorithms to predict poor outcomes and mortality. We report Odds Ratio (OR) or Hazard Ratio (HR) with 95% Confidence Interval (CI). We used five-fold cross-validation and bootstrapping for internal validation of prediction models. We included 149 patients for 90-day and 144 patients with ICH for 180-day outcome analyses. In multivariable logistic regression, UCH-L1 (adjusted OR 9.23; 95%CI 2.41-35.33), alpha-2-macroglobulin (aOR 5.57; 95%CI 1.26-24.59), and Serpin-A11 (aOR 9.33; 95%CI 1.09-79.94) were independent predictors of 90-day poor outcome; MMP-2 (aOR 6.32; 95%CI 1.82-21.90) was independent predictor of 180-day poor outcome. In multivariable Cox regression models, IGFBP-3 (aHR 2.08; 95%CI 1.24-3.48) predicted 90-day and MMP-9 (aOR 1.98; 95%CI 1.19-3.32) predicted 180-day mortality. Machine learning identified additional predictors, including haptoglobin for poor outcomes and UCH-L1, APO-C1, and MMP-2 for mortality prediction. Overall, random forest models outperformed regression models for predicting 180-day poor outcomes (AUC 0.89), and 90-day (AUC 0.81) and 180-day mortality (AUC 0.81). Serum biomarkers independently predicted short-term poor outcomes and mortality after ICH. Further research utilizing a multi-omics platform and temporal profiling is needed to explore additional biomarkers and refine predictive models for ICH prognosis.

Phosphodiesterase 4 D (PDE4D) gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Studies on the relationship between Phosphodiesterase 4 D (PDE4D) gene polymorphism with the risk of ischemic stroke (IS) have shown discordant results. The present meta-analysis was aimed to clarify the relationship between PDE4D gene polymorphism with the risk of IS by estimating pooled analysis of published epidemiological studies. METHODS: A comprehensive literature search for all the published articles was performed in various electronic databases, including PubMed, EMbase, Cochrane Library, Trip Database, Worldwide Science, CINAHL, and Google Scholar up to 22nd December 2021. Pooled Odds ratios (ORs) with 95% Confidence Intervals (CIs) under dominant, recessive, and allelic models were calculated. Subgroup analysis based on ethnicity (Caucasian vs. Asian) was performed to examine the reliability of these findings. Sensitivity analysis was also performed to detect the heterogeneity between studies. Finally, Begg's funnel plot was used to assess the potential for publication bias. RESULTS: In our meta-analysis, we identified a total of 47 case-control studies with 20,644 ischemic stroke (IS) cases and 23,201 control subjects, including 17 studies of Caucasian descent and 30 studies of Asian descent. Our findings suggest that there was a significant relationship between SNP45 gene polymorphism and risk of IS (Recessive model: OR = 2.06, 95% CI 1.31-3.23), SNP83 overall (allelic model: OR = 1.22, 95% CI 1.04-1.42), Asian (allelic model: OR = 1.20, 95% CI 1.05-1.37), and SNP89 Asian (Dominant model: OR = 1.43, 95% CI 1.29-1.59, recessive model: OR = 1.42, 95% CI 1.28-1.58) respectively. However, no significant relationship was found between SNP32, SNP41, SNP26, SNP56, and SNP87 gene polymorphisms and risk of IS. CONCLUSION: Findings of this meta-analysis conclude that SNP45, SNP83, and SNP89 polymorphism could be capable of increasing stroke susceptibility in Asians but not in the Caucasian population. Genotyping of SNP 45, 83, 89 polymorphisms may be used as a predictor for the occurrence of IS.

Blood-based protein biomarkers for the diagnosis of acute stroke: A discovery-based SWATH-MS proteomic approach.

Background and purposes: Recent developments in high-throughput proteomic approach have shown the potential to discover biomarkers for diagnosing acute stroke and to elucidate the pathomechanisms specific to different stroke subtypes. We aimed to determine blood-based protein biomarkers to diagnose total stroke (IS+ICH) from healthy controls, ischemic stroke (IS) from healthy controls, and intracerebral hemorrhage (ICH) from healthy control subjects within 24 h using a discovery-based SWATH-MS proteomic approach. Methods: In this discovery phase study, serum samples were collected within 24 h from acute stroke (IS & ICH) patients and healthy controls and were subjected to SWATH-MS-based untargeted proteomics. For protein identification, a high-pH fractionated peptide library for human serum proteins (obtained from SCIEX) comprising of 465 proteins was used. Significantly differentially expressed (SDE) proteins were selected using the following criteria: >1.5-fold change for upregulated, < 0.67 for downregulated, p-value < 0.05, and confirmed/tentative selection using Boruta random forest. Protein-protein interaction network analysis and the functional enrichment analysis were conducted using STRING 11 online tool, g:Profiler tool and Cytoscape 3.9.0 software. The statistical analyses were conducted in R version 3.6.2. Results: Our study included 40 stroke cases (20 IS, 20 ICH) within 24 h and 40 age-, sex-, hypertension-, and diabetes-matched healthy controls. We quantified 375 proteins between the stroke cases and control groups through SWATH-MS analysis. We observed 31 SDE proteins between total stroke and controls, 16 SDE proteins between IS and controls, and 41 SDE proteins between ICH and controls within 24 h. Four proteins [ceruloplasmin, alpha-1-antitrypsin (SERPINA1), von Willebrand factor (vWF), and coagulation factor XIII B chain (F13B)] commonly differentiated total stroke, IS, and ICH from healthy control subjects. The most common significant pathways in stroke cases involved complement and coagulation cascades, platelet degranulation, immune-related processes, acute phase response, lipid-related processes, and pathways related to extracellular space and matrix. Conclusion: Our discovery phase study identified potential protein biomarker candidates for the diagnosis of acute stroke and highlighted significant pathways associated with different stroke subtypes. These potential biomarker candidates warrant further validation in future studies with a large cohort of stroke patients to investigate their diagnostic performance.

Lipoprotein (a) level as a risk factor for stroke and its subtype: A systematic review and meta-analysis.

The role of lipoprotein-A [Lp (a)] as a risk factor for stroke is less well documented than for coronary heart disease. Hence, we conducted a systematic review and meta-analysis for the published observational studies in order to investigate the association of Lp (a) levels with the risk of stroke and its subtypes. In our meta-analysis, 41 studies involving 7874 ischemic stroke (IS) patients and 32,138 controls; 13 studies for the IS subtypes based on TOAST classification and 7 studies with 871 Intracerebral hemorrhage (ICH) cases and 2865 control subjects were included. A significant association between increased levels of Lp (a) and risk of IS as compared to control subjects was observed (standardized mean difference (SMD) 0.76; 95% confidence interval (CIs) 0.53-0.99). Lp (a) levels were also found to be significantly associated with the risk of large artery atherosclerosis (LAA) subtype of IS (SMD 0.68; 95% CI 0.01-1.34) as well as significantly associated with the risk of ICH (SMD 0.65; 95% CI 0.13-1.17) as compared to controls. Increased Lp (a) levels could be considered as a predictive marker for identifying individuals who are at risk of developing IS, LAA and ICH.

Association between Angiotensin Converting Enzyme Insertion/Deletion gene polymorphism with the risk of Hemorrhagic Stroke: A systematic review and Meta-Analysis of 53 studies.

BACKGROUND AND AIMS: Hemorrhagic stroke (HS) results in significant mortality and disability worldwide. Angiotensin Converting Enzyme (ACE) is responsible for blood pressure regulation and vascular homeostasis. Our objective was to conduct a comprehensive meta-analysis for ascertaining the association of ACE I/D polymorphism with HS since a number of studies depicted inconclusive evidence. METHODS: Literature search was performed till July 10, 2020 in PubMed, EMBASE, Cochrane, Chinese National Knowledge Information and Google Scholar databases with keywords: ('Angiotensin Converting Enzyme' OR 'ACE') AND ('Single Nucleotide polymorphisms' OR 'SNP') AND ('Hemorrhagic stroke or 'HS'). Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were determined for gene-disease association using either fixed (when I2 < 50%) or random effect (when I2 > 50%) models. Risk of bias in studies was assessed using funnel plots and sensitivity analyses. Statistical analysis was performed using STATA version 13.0 software. RESULTS: A total of 53 studies having 5186 HS and 7347 healthy control subjects were included in our meta-analysis. Pooled analyses showed that ACE I/D gene polymorphism had significant association with risk of HS in overall study population [(dominant model: OR = 1.29, 95% CI = 1.12-1.50 & recessive model: OR = 1.79, 95% CI = 1.46-2.20)]. Population subgroup analyses further revealed significant relationship of ACE I/D polymorphism with ICH in Asians (recessive: OR 1.97, 95% CI = 1.57-2.47) but not in Caucasians (recessive: OR 1.02, 95% CI = 0.76-1.36). CONCLUSION: This meta-analysis suggests that ACE I/D polymorphism may lead to risk of HS and can be a potential biomarker for HS susceptibility especially in Asian population.

Micro-embolic signal monitoring in stroke subtypes: A systematic review and meta-analysis of 58 studies.

Introduction: Micro-embolic signals (MESs) detected using transcranial Doppler (TCD) help in risk stratification in stroke patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke recurrence, functional outcome, and mortality in different stroke subtypes. Methods: A comprehensive literature search was conducted before 26th January 2021 in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies were identified that used TCD to detect MES in stroke/TIA patients. Pooled prevalence and odds ratio (OR) along with 95% confidence interval (95% CI) were calculated for different outcome measures. The entire statistical analysis was conducted in R version 3.6.2. Findings: Fifty-eight studies involving 5123 patients (1329 MES+, 3794 MES-) were included in our meta-analysis. The pooled prevalence of MES among all acute stroke/TIA patients was 30% (95% CI 25-34%). The pooled prevalence adjusted after the trim-and-fill analysis among all acute stroke/TIA patients was 18% (95% CI 14-23%). The prevalence of MES was high among all stroke subtypes except in patients with small vessel disease (SVD). In patients with new-onset stroke/TIA, the presence of MES was associated with a high risk of recurrence of cerebral ischemia (OR 4.03; 95% CI 2.38-6.82). Although no significant association was observed for the presence of MES with increased mortality (OR 2.37; 95% CI 0.75-7.50) and poor functional outcome (OR 2.11; 95% CI 0.20-22.50) among patients with new-onset stroke/TIA, this could only be determined in a smaller sample size of 477 patients. Conclusions: Our meta-analysis showed a 30% prevalence of MES following acute stroke/TIA. The presence of MES increased the chance of recurrence of cerebral ischemia but was not associated with poor functional outcomes and mortality in the studied subgroup.

Relationship between methylenetetrahydrofolate reductase (MTHFR) gene (A1298C) polymorphism with the risk of stroke: A systematic review and meta-analysis.

Studies on relationship between methylenetetrahydrofolate reductase gene (MTHFR) gene A1298C polymorphism with the risk of ischemic as well as hemorrhagic stroke have shown discordant results. Present meta-analysis was aimed to clarify the relationship between MTHFR gene A1298C polymorphism with risk of stroke. A comprehensive literature search for all published articles was performed in electronic database including PubMed, EMbase, Cochrane Library, Trip Databases, Worldwide Science, CINAHL, and Google Scholar up to 31st  December 2019. Pooled odds ratio (ORs) with 95% confidence interval (CIs) under dominant, recessive, and allelic models was calculated. Sensitivity analysis was also performed to detect the heterogeneity. In our meta-analysis, a total of 20 studies with 19 case control studies involving 2871 ischemic stroke (IS) cases and 3984 controls and 3 studies with 201 hemorrhagic stroke cases and 1349 controls were included. Our findings suggest that there was a significant relationship between MTHFR gene A1298C gene polymorphism with risk of ischemic stroke (dominant model: OR = 1.32, 95% CI = 1.06-1.66, recessive model: OR = 1.45, 95% CI = 1.06-1.99 and allelic model: OR = 1.35, 95% CI = 1.00-1.84, respectively). However, no significant relationship between MTHFR gene A1298C gene polymorphism with the risk of hemorrhagic stroke. Findings of this meta-analysis concludes that MTHFR gene A1298 C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian population. Genotyping of MTHFR gene A1298C polymorphism may be used as a predictor for the occurrence of ischemic stroke.

Blood biomarkers for the diagnosis and differentiation of stroke: A systematic review and meta-analysis.

BACKGROUND: Correct diagnosis of stroke and its subtypes is pivotal in early stages for optimum treatment. AIMS: The aim of this systematic review and meta-analysis is to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of stroke subtypes. METHODS: A literature search was conducted for papers published until 20 April 2020 in PubMed, EMBASE, Cochrane Library, TRIP, and Google Scholar databases to search for eligible studies investigating the role of blood biomarkers in diagnosing stroke. Quality assessment was done using modified Quality Assessment of Diagnostic Accuracy Studies questionnaire. Pooled standardized mean difference and 95% confidence intervals were calculated. Presence of heterogeneity among the included studies was investigated using the Cochran's Q statistic and I2 metric tests. If I2 was < 50% then a fixed-effect model was applied else a random-effect model was applied. Risk of bias was assessed using funnel plots and between-study heterogeneity was assessed using meta-regression and sensitivity analyses. Entire statistical analysis was conducted in STATA version 13.0. RESULTS: A total of 40 studies including patients with 5001 ischemic strokes, 756 intracerebral hemorrhage, 554 stroke mimics, and 1774 healthy control subjects analyzing 25 biomarkers (within 24 h after symptoms onset/after the event) were included in our meta-analysis; 67.5% of studies had moderate evidence of quality. Brain natriuretic peptide, matrix metalloproteinase-9, and D-dimer significantly differentiated ischemic stroke from intracerebral hemorrhage, stroke mimics, and health control subjects (p < 0.05). Glial fibrillary acidic protein successfully differentiated ischemic stroke from intracerebral hemorrhage (standardized mean difference -1.04; 95% confidence interval -1.46 to -0.63) within 6 h. No studies were found to conduct a meta-analysis of blood biomarkers differentiating transient ischemic attack from healthy controls and stroke mimics. CONCLUSION: This meta-analysis highlights the potential of brain natriuretic peptide, matrix metalloproteinase-9, D-dimer, and glial fibrillary acidic protein as diagnostic biomarkers for stroke within 24 h. Results of our meta-analysis might serve as a platform for conducting further targeted proteomics studies and phase-III clinical trials.PROSPERO Registration ID: CRD42019139659.

Global impact of environmental temperature and BCG vaccination coverage on the transmissibility and fatality rate of COVID-19.

The 2019-Coronavirus (COVID-19) pandemic has had a global impact. The effect of environmental temperature on transmissibility and fatality rate of COVID-19 and protective efficacy of Bacillus Calmette-Guérin (BCG) vaccination towards COVID-19 remains ambiguous. Therefore, we explored the global impact of environmental temperature and neonatal BCG vaccination coverage on transmissibility and fatality rate of COVID-19. The COVID-19 data for reported cases, deaths and global temperature were collected from 31st December 2020 to 3rd April 2020 for 67 countries. Temperature data were split into quartiles for all three categories (minimum temperature, maximum temperature and mean temperature). The impact of three types of temperature data and policy of BCG vaccination on COVID-19 infection was determined by applying the multivariable two-level negative binomial regression analysis keeping daily new cases and daily mortality as outcome. The highest number of cases fell in the temperature categories as following: mean temperature in the second quartile (6°C to 10.5°C), median 26, interquartile range (IQR) 237; minimum temperature in the first quartile (-26°C to 1°C), median 23, IQR 173; maximum temperature in the second quartile (10°C to 16°C), median 27.5, IQR 219. For the minimum temperature category, 28% statistically significant lower incidence was noted for new cases from the countries falling in the second quartile (2°C to 6°C) compared with countries falling in the first quartile (-26°C to 1°C) (incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.57 to 0.93). However, no statistically significant difference in incidence rate was observed for mean temperature categories in comparison to the first quartile. Countries with BCG vaccination policy had 58% less mortality as compared with countries without BCG coverage (IRR 0.42; 95% CI 0.18 to 0.95). Our exploratory study provides evidence that high temperature might not be associated with low transmissibility and countries having neonatal BCG vaccination policy had a low fatality rate of COVID-19.