Association between Apolipoprotein E Polymorphism and Clinical Outcome after Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage

2021 ◽  
pp. 1-10
Author(s):  
Wen Pan ◽  
Min Zhang ◽  
Zhenping Guo ◽  
Wenfeng Xiao ◽  
Chao You ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Clinical Outcome ◽  
Intracerebral Hemorrhage ◽  
Apolipoprotein E ◽  
Functional Outcomes ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Fixed Effects Models ◽  
Increased Risk

<b><i>Backgrounds:</i></b> Previous studies reported inconsistent results regarding associations between apolipoprotein E (<i>APOE</i>) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Methods:</i></b> To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Results:</i></b> Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, <i>I</i><sup>2</sup> = 29.4%, <i>p</i> = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, <i>I</i><sup>2</sup> = 15.6%, <i>p</i> = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, <i>I</i><sup>2</sup> = 0.0%, <i>p</i> = 0.543). Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, <i>I</i><sup>2</sup> = 57.1%, <i>p</i> = 0.022). <b><i>Conclusions:</i></b> In conclusion, the present study demonstrated <i>APOE</i> ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH.

scholarly journals Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)

2018 ◽  
Vol 13 (5) ◽  
pp. 454-468 ◽  
Author(s):  
Andreas Charidimou ◽  
Sara Shams ◽  
Jose R Romero ◽  
Jie Ding ◽  
Roland Veltkamp ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Intracerebral Hemorrhage ◽  
Meta Analysis ◽  
Population Based ◽  
Cerebral Microbleeds ◽  
Clinical Settings ◽  
Memory Clinic ◽  
Increased Risk ◽  
Stroke Death

Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

Abstract WMP60: Association Between Liver Cirrhosis and Stroke in a Nationally Representative Cohort

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Neal S Parikh ◽  
Babak B Navi ◽  
Yecheskel Schneider ◽  
Hooman Kamel
Keyword(s):  
Risk Factors ◽  
Liver Cirrhosis ◽  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Intracerebral Hemorrhage ◽  
Cox Proportional Hazards ◽  
Medicare Beneficiaries ◽  
Stroke Incidence ◽  
Increased Risk ◽  
Thrombotic Complications

Introduction: Liver cirrhosis is characterized by a coagulopathy associated with both hemorrhagic and thrombotic complications. However, the risk of stroke - hemorrhagic and ischemic - in patients with cirrhosis has not been rigorously assessed. Methods: We performed a retrospective cohort study of Medicare beneficiaries ≥66 years of age using a 5% sample of inpatient and outpatient claims from 2008-2014. Our predictor was liver cirrhosis, defined by presence of at least two ICD-9-CM inpatient or outpatient claims for liver cirrhosis or its complications, a validated algorithm previously used to study cirrhosis in Medicare beneficiaries. The primary outcome was stroke, and the secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Outcomes were defined by validated ICD-9-CM algorithms. Patients were censored at the time of an outcome, death, or on December 31, 2014. We used survival analysis to compare stroke incidence in patients with and without liver cirrhosis. Cox proportional hazards analysis was used to evaluate the association between cirrhosis and stroke while adjusting for demographics and established stroke risk factors. Results: Among the 1,564,277 beneficiaries in our sample, we identified 10,512 (0.7%) patients with liver cirrhosis. The mean age of patients with cirrhosis was 74.1 (±6.5) years. Over a median follow-up of 5 years, 76,195 patients were hospitalized with a stroke. The incidence of stroke was 1.9% (95% confidence interval [CI], 1.7-2.1%) per year in patients with cirrhosis and 1.1% (95% CI, 1.1-1.1%) per year in patients without cirrhosis. After adjusting for demographics and vascular risk factors, patients with cirrhosis experienced a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.2-1.5); however, associations appeared more robust for intracerebral hemorrhage (HR, 2.2; 95% CI, 1.7-2.8) and subarachnoid hemorrhage (HR, 2.0; 95% CI, 1.2-3.1) than for ischemic stroke (HR, 1.3; 95% CI, 1.1-1.4). Conclusions: We found that liver cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. Our results build on recent work investigating the hemorrhagic and thrombotic complications of liver cirrhosis outside of the portal circulation.

scholarly journals Prognostic Value of Blood Pressure Variability for Patients With Acute or Subacute Intracerebral Hemorrhage: A Meta-Analysis of Prospective Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Weidong Liu ◽  
Xianbo Zhuang ◽  
Liyong Zhang
Keyword(s):  
Blood Pressure ◽  
Standard Deviation ◽  
Intracerebral Hemorrhage ◽  
Prospective Studies ◽  
Functional Outcomes ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Increased Risk ◽  
Poor Outcomes

The results on the role of systolic blood pressure (SBP) variability in the functional outcome for patients with intracerebral hemorrhage (ICH) have been inconsistent. Hence, this meta-analysis of prospective studies was conducted to assess the association between SBP variability and poor outcomes in patients with acute or subacute ICH. PubMed, Embase, and the Cochrane Library were electronically searched for eligible studies from their inception to July 2020. The role of SBP variability assessed using standard deviation (SD), coefficient of variation (CV), successive variation (SV), average real variability (ARV), and residual standard deviation (RSD) in the risk of poor functional outcomes were assessed using odds ratio (OR) with 95% confidence interval (CI) through the random-effects model. Seven prospective studies involving 5,201 patients with ICH were selected for the final meta-analysis. Increased SBP variability was associated with an increased risk of poor functional outcomes, regardless of its assessment using SD (OR: 1.38; 95% CI: 1.14–1.68; P = 0.001), CV (OR: 1.98; 95% CI: 1.13–3.47; P = 0.017), SV (OR: 1.30; 95% CI: 1.08–1.58; P = 0.006), ARV (OR: 1.13; 95% CI: 1.03–1.24; P = 0.010), or RSD (OR: 1.22; 95% CI: 1.00–1.50; P = 0.049). Moreover, the role of SBP variability in the risk of poor functional outcomes for patients with ICH was affected by country, study design, mean age, stroke type, outcome definition, and study quality. This study indicated that SBP variability was a predictor of poor outcomes for patients with ICH.

scholarly journals Association of Natriuretic Peptide With Adverse Outcomes and Disease Severity After Intracerebral Hemorrhage: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Wang ◽  
Jingxuan Wang ◽  
Zhouping Tang ◽  
Ping Zhang
Keyword(s):  
Clinical Outcome ◽  
Intracerebral Hemorrhage ◽  
Disease Severity ◽  
Natriuretic Peptide ◽  
Functional Outcomes ◽  
Cardiac Events ◽  
Poor Functional Outcome ◽  
Increased Risk ◽  
Adverse Cardiac Events ◽  
All Cause Mortality

Background: Over the past decade, many studies have reported the association of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with clinical outcome of intracerebral hemorrhage (ICH). However, a broad consensus has not been reached.Objective: To evaluate the role of BNP/NT-proBNP levels in prognosis and disease severity assessment in patients with ICH.Methods: A systematic literature search was conducted utilizing PubMed, Embase, Web of Science and the Cochrane Library databases up to July 23, 2021. Studies that explored the association between BNP/NT-proBNP level and clinical outcome or disease severity in ICH patients were eligible. Outcome measures were all-cause mortality, poor functional outcome, adverse cardiac events and markers of disease severity.Results: Ten studies, involving 1,373 patients with ICH, met the inclusion criteria. Nine studies focused on clinical outcomes (five all-cause mortality, five functional outcomes, and one adverse cardiac event) and seven on disease severity. In terms of prognosis, all five studies showed an association between elevated BNP/NT-proBNP level and increased risk of all-cause mortality in ICH patients. Four of the five studies reported poor functional outcomes in patients with higher BNP/NT-proBNP levels and one study associated higher BNP/NT-proBNP levels with increased risk of adverse cardiac events. Moreover, two studies identified an additional predictive ability of BNP/NT-proBNP level beyond that of pre-existing prognostic variables. In terms of disease severity, five studies (71%) reported that BNP/NT-proBNP level correlated positively with hematoma volume in addition to ICH and GCS scores.Conclusion: Elevated BNP/NT-proBNP level is associated with increased risk of all-cause mortality, poor functional outcome, adverse cardiac events and disease severity in patients with ICH. Thus, BNP/NT-proBNP level is a promising prognostic indicator for ICH and also an effective marker of disease severity. Current evidence remains limited by the small number and high heterogeneity of included studies. Further appropriately designed, large-scale studies are required to confirm the current findings.

scholarly journals Does Apolipoprotein E Genotype Influence the Risk of Ischemic Stroke, Intracerebral Hemorrhage, or Subarachnoid Hemorrhage?

Stroke ◽  
2006 ◽  
Vol 37 (2) ◽  
pp. 364-370 ◽  
Author(s):  
Cathie Sudlow ◽  
Nahara Ananí Martínez González ◽  
Jennifer Kim ◽  
Catriona Clark
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Intracerebral Hemorrhage ◽  
Apolipoprotein E ◽  
Apolipoprotein E Genotype

scholarly journals Differences in risk factors for 3 types of stroke

Neurology ◽  
2018 ◽  
Vol 90 (4) ◽  
pp. e298-e306 ◽  
Author(s):  
Alison J. Price ◽  
F. Lucy Wright ◽  
Jane Green ◽  
Angela Balkwill ◽  
Sau Wan Kan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Intracerebral Hemorrhage ◽  
Cox Regression ◽  
Related Factors ◽  
Stroke Incidence ◽  
Relative Risks ◽  
Increased Risk ◽  
Meta Analyses

ObjectiveTo compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke.MethodsA total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999–2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies.ResultsAfter 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84–2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04–1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26–0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30–1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12–5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94–2.72] or ischemic stroke [RR 2.50, 95% CI 2.29–2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke.ConclusionClassic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

scholarly journals Obesity Is Associated with Severe Disease and Mortality in Patients with Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Zixin Cai ◽  
Yan Yang ◽  
Jingjing Zhang
Keyword(s):  
Fixed Effects ◽  
Web Of Science ◽  
Meta Analysis ◽  
Severe Disease ◽  
Cochrane Library ◽  
Obese Patients ◽  
Risk Of Infection ◽  
Fixed Effects Models ◽  
Increased Risk ◽  
Nonobese Patients

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has led to global research with the aim of predicting which people are at greatest risk of developing severe disease and dying. The aim of this meta-analysis was to determine the associations between obesity and the severity of and mortality due to COVID-19. Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies evaluating the associations of obesity with COVID-19 . Odd risks (ORs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Results: Thirty-eight studies involving 621502 patients were included. Compared with nonobese patients, obese patients had a significantly increased risk of infection (OR 3.19, 95% CI 1.45-7.03; I2 = 98.3%), hospitalization (OR 1.77, 95% CI 1.61-1.95; I2 = 43.8%), clinically severe disease (OR 2.88, 95% CI 1.99-4.16; I2 = 49.9%), mechanical ventilation (OR 1.66, 95% CI1.42-1.94; I2 = 41.3%), intensive care unit (ICU) (OR 2.06, 95% CI1.49-2.85; I2 = 71.4%), and mortality (OR 1.48, 95% CI 1.18-1.85; I2 = 80.8%). Conclusion: Patients with obesity may have a greater risk of developing severe COVID-19 and dying. Therefore, it is important to increase awareness of these associations with obesity in COVID-19 patients.

scholarly journals Triglyceride-glucose index and the risk of stroke and its subtypes in the general population: an 11-year follow-up

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Anxin Wang ◽  
Guangyao Wang ◽  
Qian Liu ◽  
Yingting Zuo ◽  
Shuohua Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
General Population ◽  
Intracerebral Hemorrhage ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Tyg Index ◽  
Increased Risk

Abstract Background Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort. Methods A total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006–2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression. Results During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12–1.33, and adjusted HR 1.32, 95% CI 1.21–1.44, respectively, P for trend < 0.001). We also found a linear association between baseline TyG index with stroke. Similar results were found for ischemic stroke. However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage. Parallel results were observed for the associations of updated cumulative average TyG index with outcomes. Conclusions Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.

scholarly journals The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zonglei Zhou ◽  
Ruzhen Zhou ◽  
Kunpeng Li ◽  
Wen Wei ◽  
Zengqiao Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Sensitivity Analysis ◽  
Parkinson's Disease ◽  
Toxoplasma Gondii ◽  
Publication Bias ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Fixed Effects Models ◽  
Increased Risk

Background. Several studies have investigated the association between Toxoplasma gondii (T. gondii) infection and risk of Parkinson’s disease (PD) with inconsistent results. Clarifying this relation might be useful for better understanding of the risk factors and the relevant mechanisms of PD, thus a meta-analysis was conducted to explore whether exposure to T. gondii is associated with an increased risk of PD. Methods. We conducted this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A rigorous literature selection was performed by using the databases of PubMed, Embase, Web of Science, Cochrane Library, and ScienceDirect. Odds ratio (OR) and corresponding 95% confidential interval (CI) were pooled by using fixed-effects models. Sensitivity analysis, publication bias test, and methodological quality assessment of studies were also performed. Results. Seven studies involving 1086 subjects were included in this meta-analysis. Pooled data by using fixed-effects models suggested both latent infection (OR, 1.17; 95% CI, 0.86 to 1.58; P=0.314) and acute infection (OR, 1.13; 95% CI, 0.30 to 4.35; P=0.855) were not associated with PD risk. Stable and robust estimates were confirmed by sensitivity analysis. No publication bias was found by visual inspection of the funnel plot, Begg’s, and Egger’s test. Conclusions. This meta-analysis does not support any possible association between T. gondii infection and risk of PD. Researches are still warranted to further explore the underlying mechanisms of T. gondii in the pathogenesis of PD and their causal relationship.

scholarly journals Sleep-disordered breathing-related symptoms and risk of stroke: cohort study and Mendelian randomization analysis

2021 ◽  
Author(s):  
Olga E. Titova ◽  
Shuai Yuan ◽  
John A. Baron ◽  
Eva Lindberg ◽  
Karl Michaëlsson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Sleep Apnea ◽  
Confidence Interval ◽  
Intracerebral Hemorrhage ◽  
Sleep Disordered Breathing ◽  
Mendelian Randomization ◽  
Genome Wide ◽  
Increased Risk

Abstract Background Sleep-disordered breathing (SDB) may contribute to development of stroke. However, findings are inconclusive. We investigated whether SDB-related symptoms are associated with incidence of stroke and its types in a general community sample of adult men and women as well as to perform Mendelian randomization (MR) analysis. Methods We used data from a cohort of 41,742 Swedish adults (56–94 years of age) who completed questionnaires regarding snoring, cessation of breathing, lifestyle and health characteristics. Participants were followed up for incident stroke and death over 8 years through linkage to the Swedish Registers. Hazard ratios, adjusted for potential confounders, were estimated by Cox proportional hazards regression. MR analyses were performed using single-nucleotide polymorphisms associated with sleep apnea at the genome-wide significance level and summary-level data for stroke and its subtypes from consortia and a meta-analysis of Genome-Wide Association Studies. Results In the cohort study, symptoms of disturbing snoring and/or cessation of breathing were associated with increased risk of total stroke (hazard ratio 1.12, 95% confidence interval 1.02–1.24) and intracerebral hemorrhage (hazard ratio 1.59, 95% confidence interval 1.23–2.05) but not with ischemic stroke or subarachnoid hemorrhage. MR analyses showed no association of genetic liability to sleep apnea with the risk of overall stroke or any specific types of stroke or ischemic stroke subtypes. Conclusions SDB-related symptoms were associated with increased risk of total stroke, specifically intracerebral hemorrhage, in the observational analyses but not in the MR analyses. There was limited evidence of an association of SDB with ischemic stroke and subarachnoid hemorrhage.

Sign in / Sign up

Export Citation Format

Share Document