Serum levels of Trimethylamine-N-oxide in patients with ischemic stroke

Abstract Objective: Accumulating evidence suggests that Trimethylamine-N-oxide (TMAO), a gut microbial metabolite, is implicated in the pathogenesis of many cardiovascular diseases. The aim of the present study was to investigate the serum levels of TMAO in Chinese patients with ischemic stroke. Method: In the present study, 255 consecutive patients with first-ever acute ischemic stroke and 255 age and gender-matched healthy volunteers were included for testing serum TMAO. Stroke severity was determined by the NIH Stroke Scale (NIHSS). The stroke severity was dichotomized as minor (NIHSS ≤ 5) and moderate-to-high clinical severity (NIHSS > 6). Results: The serum levels of TMAO in stroke ranged from 0.5 to 18.3 μM, with a median value of 5.8 (interquartile range (IQR), 3.3–10.0) μM, which was higher than in those controls (3.9; IQR, 2.6–6.1 μM). The median level of TMAO in those patients was significantly lower than in those moderate-to-high stroke patients (4.1 μM [IQR, 2.8–6.2] vs. 9.1 μM [5.1–11.0]; P<0.001). In univariate and multivariable models, the unadjusted risk of moderate-to-high stroke was increased by 31% (odds ratio (OR) = 1.31 [95% confidence interval (CI): 1.21–1.42], P<0.001) and 22% (OR = 1.22; 95% CI = 1.08–1.32; P<0.001), when TMAO was increased each by 1 μM. Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value of serum level of TMAO as an indicator for screening of moderate-to-high stroke was estimated to be 6.6 μM, which yielded a sensitivity of 69.3 % and a specificity of 79.0%, with the area under the curve at 0.750 (95% CI, 0.687–0.812). Conclusions: Higher TMAO levels were associated with increased risk of first ischemic stroke and worse neurological deficit in Chinese patients.

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Reduced serum BDNF levels are associated with the increased risk for developing MDD: A case-control study with or without antidepressants therapy

10.21203/rs.2.18282/v1 ◽

2019 ◽

Author(s):

Md. Prova Zaman Emon ◽

Rajesh Das ◽

Nuruna Lovely Nishuty ◽

M.M.A. Shalahuddin Qusar ◽

Mohiuddin Ahmed Bhuiyan ◽

...

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Increased Risk ◽

Drug Naïve ◽

Control Study ◽

Serum Bdnf

Abstract Objective We do not have any consistent markers for major depressive disorder (MDD) though various biological factors are involved in the pathophysiology. We aimed to evaluate the serum brain-derived neurotrophic factor (BDNF) levels in MDD patients with or without antidepressant therapy compared to healthy controls (HCs). Results We assessed serum BDNF levels among three groups: drug-naïve MDD patients (n = 41), drug-treated MDD patients (n = 44), and age-and sex-matched HCs (n = 82). Serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. Serum levels of BDNF were detected significantly lower in drug-naïve MDD patients compared to HCs. No significant alterations of serum BDNF levels between drug-treated patients and HCs were identified. Significant negative correlations between serum BDNF levels and Hamilton depression rating (Ham-D) scores were observed in both drug-naïve and drug-treated MDD patients. Receiver operating characteristic (ROC) analysis showed good diagnostic value for serum BDNF levels in drug-naïve MDD patients with the area under the curve at 0.821. The present study suggests that low serum BDNF levels may be involved in the pathophysiology of MDD. The reduced serum BDNF levels might be used as an early risk assessment marker for major depression.

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Reduced serum BDNF levels are associated with the increased risk for developing MDD: A case-control study with or without antidepressants therapy

10.21203/rs.2.23297/v1 ◽

2020 ◽

Author(s):

Md. Prova Zaman Emon ◽

Rajesh Das ◽

Nuruna Lovely Nishuty ◽

M.M.A. Shalahuddin Qusar ◽

Mohiuddin Ahmed Bhuiyan ◽

...

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Increased Risk ◽

Drug Naïve ◽

Control Study ◽

Serum Bdnf

Abstract ObjectiveWe do not have any consistent markers for major depressive disorder (MDD) though various biological factors are involved in the pathophysiology. We aimed to evaluate the serum brain-derived neurotrophic factor (BDNF) levels in MDD patients with or without antidepressant therapy compared to healthy controls (HCs).ResultsWe assessed serum BDNF levels among three groups: drug-naïve MDD patients (n = 41), drug-treated MDD patients (n = 44), and age-and sex-matched HCs (n = 82). Serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. Serum levels of BDNF were detected significantly lower in drug-naïve MDD patients compared to HCs. No significant alterations of serum BDNF levels between drug-treated patients and HCs were identified. Significant negative correlations between serum BDNF levels and Hamilton depression rating (Ham-D) scores were observed in both drug-naïve and drug-treated MDD patients. Receiver operating characteristic (ROC) analysis showed good diagnostic value for serum BDNF levels in drug-naïve MDD patients with the area under the curve at 0.821. The present study suggests that low serum BDNF levels may be involved in the pathophysiology of MDD. The reduced serum BDNF levels might be used as an early risk assessment marker for major depression.

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SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy

Journal of Neurology ◽

10.1007/s00415-021-10620-8 ◽

2021 ◽

Author(s):

Alessandro Pezzini ◽

◽

Mario Grassi ◽

Giorgio Silvestrelli ◽

Martina Locatelli ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Classification Performance ◽

Clinical Severity ◽

Hospital Death ◽

Stroke Severity ◽

Good Recall ◽

Laboratory Parameters ◽

Model Based ◽

Increased Risk

Abstract Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. Results Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17–5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. Conclusions Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

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Dysphagia screening after intracerebral hemorrhage

International Journal of Stroke ◽

10.1177/1747493017729265 ◽

2017 ◽

Vol 13 (5) ◽

pp. 503-510 ◽

Cited By ~ 1

Author(s):

Raed A Joundi ◽

Rosemary Martino ◽

Gustavo Saposnik ◽

Vasily Giannakeas ◽

Jiming Fang ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Stroke ◽

Clinical Severity ◽

Stroke Severity ◽

Stroke Registry ◽

Patients At Risk ◽

Poor Outcomes ◽

Risk Of Aspiration ◽

To Receive

Background Dysphagia screening is recommended after acute stroke to identify patients at risk of aspiration and implement appropriate care. However, little is known about the frequency and outcomes of patients undergoing dysphagia screening after intracerebral hemorrhage (ICH). Methods We used the Ontario Stroke Registry from 1 April 2010 to 31 March 2013 to identify patients hospitalized with acute stroke and to compare dysphagia screening rates in those with ICH and ischemic stroke. In patients with ICH we assessed predictors of receiving dysphagia screening, predictors of failing screening, and outcomes after failing screening. Results Among 1091 eligible patients with ICH, 354 (32.4%) patients did not have documented dysphagia screening. Patients with mild ICH were less likely to receive screening (40.4% of patients were omitted, adjusted odds ratio (aOR) 0.40, 95% confidence interval (CI) 0.26–0.63). Older age, greater stroke severity, speech deficits, lower initial level of consciousness, and admission to intensive care unit were predictive of failing the screening test. Failing screening was associated with poor outcomes, including pneumonia (aOR 5.3, 95% CI 2.36–11.88), severe disability (aOR 4.78, 95% CI 3.08–7.41), and 1-year mortality (adjusted hazard ratio 2.1, 95% CI 1.38–3.17). When compared to patients with ischemic stroke, patients with ICH were less likely to receive dysphagia screening (aOR 0.64, 95% CI 0.54–0.76) and more likely to fail screening (aOR 1.98, 95% 1.62–2.42). Conclusion One-third of patients with ICH did not have documented dysphagia screening, increasing to 40% in patients with mild clinical severity. Failing screening was associated with poor outcomes. Patients with ICH were less like to receive screening and twice as likely to fail compared to patients with ischemic stroke, and thus efforts should be made to include ICH patients in dysphagia screening protocols whenever possible.

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Abstract WP286: Race and Gender Differences Among Patients With First or Recurrent Ischemic Stroke

Stroke ◽

10.1161/str.47.suppl_1.wp286 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Mary G George ◽

Xin Tong

Keyword(s):

Gender Differences ◽

Ischemic Stroke ◽

Recurrent Stroke ◽

Hospital Death ◽

Stroke Severity ◽

Race And Gender ◽

Black Females ◽

White Males ◽

Black Patients ◽

And Gender

Introduction: Little information is known about the race and gender differences in stroke severity of acute ischemic stroke (AIS) among those presenting with and without a recurrent stroke (RS). Methods: The study is limited to white and black patients who were admitted with an AIS in the Paul Coverdell National Acute Stroke Program from 2012-2014. There were 157 967 admissions from 453 hospitals identified. After excluding those with missing NIHSS (33 017), the analysis focused on 124 950 patients. Results: The median age of blacks and females was greater than for whites and males, 74 vs 63 and 75 vs 68, respectively. RS accounted for 21.8% of AIS in white males, 21.2% in white females, 28.3% in black males, and 30.0% in black females. The median NIHSS was higher among females with initial stroke or RS stroke (4.0 vs 3.0 and 5.0 vs 4.0, respectively, p<0.0001) and higher among blacks with initial stroke or RS (4.0 vs 3.0 and 5.0 vs 4.0, respectively, p<0.0001). Overall in-hospital death was greater among whites and females compared to blacks and males (4.1% vs 2.9%, p<0.0001; 4.2% vs 3.5%, p<0.0001, respectively), and this pattern was consistent for initial AIS and RS. Use of tPA was greater among whites and males compared to blacks and females (11.6% vs 10.3%, p<0.0001; 11.5 vs 11.1%, p=0.02, respectively). This pattern was consistent for initial AIS and RS by race and for initial AIS by gender, but not for tPA for RS by gender. Females and blacks were less likely to have a mild stroke (NIHSS score 0-4) than males and whites for both initial and RS (p<0.0001). After adjusting for age, state, hospital, and year, the odds of having an NIHSS ≥5 was 16% lower among males, 36% greater among blacks, and 38% greater for those with a RS (data not shown). Conclusion: Race and gender differences on age, stroke severity, receipt of tPA, and in-hospital death among initial AIS patients persist for RS. Blacks, females, and those with a RS have more severe AIS.

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Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization

Brain Sciences ◽

10.3390/brainsci10110771 ◽

2020 ◽

Vol 10 (11) ◽

pp. 771

Author(s):

Milena Świtońska ◽

Natalia Piekuś-Słomka ◽

Artur Słomka ◽

Paweł Sokal ◽

Ewa Żekanowska ◽

...

Keyword(s):

Ischemic Stroke ◽

Multivariable Analysis ◽

Area Under The Curve ◽

Intravenous Thrombolysis ◽

Hemorrhagic Transformation ◽

Neutrophil To Lymphocyte Ratio ◽

Study Endpoint ◽

Stroke Treatment ◽

Lymphocyte Ratio ◽

Increased Risk

Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.

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Plasma Osteoprotegerin Correlates with Stroke Severity and the Occurrence of Microembolic Signals in Patients with Acute Ischemic Stroke

Disease Markers ◽

10.1155/2019/3090364 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Yanyan Cao ◽

Congxian Cui ◽

Hongqin Zhao ◽

Xudong Pan ◽

Wenjian Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Operating Characteristic ◽

Characteristic Curve ◽

National Institutes Of Health ◽

Atherosclerotic Plaques ◽

Stroke Severity ◽

Large Artery ◽

Unstable Plaque ◽

Cutoff Value ◽

Operating Characteristic Curve

Background. Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs. Methods. Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale. Results. Plasma OPG levels were significantly associated with stroke, MESs, and stroke severity at admission (adjusted OR [95% CI]: 1.002 [1.001–1.003] p<0.001; 1.002 [1.001–1.003] p=0.001; 1.001 [1.000–1.002] p=0.028). When plasma OPG levels were used to determine the stroke severity, the area under the receiver-operating characteristic curve (AUC) was 0.734 (95% CI: 0.625-0.843) based on a cutoff value of 1998.44 pg/ml; the sensitivity and specificity of this test were 80.6% and 65.6%, respectively. Furthermore, when the levels of OPG were used to distinguish the presence of MESs, the AUC was 0.766 (95% CI: 0.672-0.860); the cutoff value was 2107.91 pg/ml. The sensitivity of this cutoff value was 68.8% and the specificity was 73.7%. Conclusions. Plasma OPG levels correlate with stroke severity and the occurrence of MESs.

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Predicting Early Mortality of Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.118.022863 ◽

2019 ◽

Vol 50 (2) ◽

pp. 349-356 ◽

Cited By ~ 11

Author(s):

Thomas Gattringer ◽

Alexandra Posekany ◽

Kurt Niederkorn ◽

Michael Knoflach ◽

Birgit Poltrum ◽

...

Keyword(s):

Ischemic Stroke ◽

Stroke Unit ◽

Functional Disability ◽

Area Under The Curve ◽

Early Mortality ◽

Stroke Severity ◽

Stroke Patients ◽

Derivation Cohort ◽

Temporal Validation

Background and Purpose— Several risk factors are known to increase mid- and long-term mortality of ischemic stroke patients. Information on predictors of early stroke mortality is scarce but often requested in clinical practice. We therefore aimed to develop a rapidly applicable tool for predicting early mortality at the stroke unit. Methods— We used data from the nationwide Austrian Stroke Unit Registry and multivariate regularized logistic regression analysis to identify demographic and clinical variables associated with early (≤7 days poststroke) mortality of patients admitted with ischemic stroke. These variables were then used to develop the Predicting Early Mortality of Ischemic Stroke score that was validated both by bootstrapping and temporal validation. Results— In total, 77 653 ischemic stroke patients were included in the analysis (median age: 74 years, 47% women). The mortality rate at the stroke unit was 2% and median stay of deceased patients was 3 days. Age, stroke severity measured by the National Institutes of Health Stroke Scale, prestroke functional disability (modified Rankin Scale >0), preexisting heart disease, diabetes mellitus, posterior circulation stroke syndrome, and nonlacunar stroke cause were associated with mortality and served to build the Predicting Early Mortality of Ischemic Stroke score ranging from 0 to 12 points. The area under the curve of the score was 0.879 (95% CI, 0.871–0.886) in the derivation cohort and 0.884 (95% CI, 0.863–0.905) in the validation sample. Patients with a score ≥10 had a 35% (95% CI, 28%–43%) risk to die within the first days at the stroke unit. Conclusions— We developed a simple score to estimate early mortality of ischemic stroke patients treated at a stroke unit. This score could help clinicians in short-term prognostication for management decisions and counseling.

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Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke

Stroke ◽

10.1161/strokeaha.118.024232 ◽

2019 ◽

Vol 50 (4) ◽

pp. 1013-1016 ◽

Cited By ~ 8

Author(s):

Hong-Qiu Gu ◽

Zhen-Zhen Rao ◽

Xin Yang ◽

Chun-Juan Wang ◽

Xing-Quan Zhao ◽

...

Keyword(s):

Ischemic Stroke ◽

Emergency Medical Services ◽

Chinese Patients ◽

Tissue Type ◽

Medical Services ◽

Stroke Severity ◽

Emergency Medical ◽

Early Arrival ◽

Timely Treatment ◽

Iv Tpa

Background and Purpose— Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods— We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates’ balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results— Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95–2.20] for onset-to-door time ≤2 hours, 2.32 [2.18–2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88–3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62–1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70–1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions— Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

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Changes in Activated Thrombin-Activatable Fibrinolysis Inhibitor Levels Following Thrombolytic Therapy in Ischemic Stroke Patients Correlate with Clinical Outcome

Cerebrovascular Diseases ◽

10.1159/000447722 ◽

2016 ◽

Vol 42 (5-6) ◽

pp. 404-414 ◽

Cited By ~ 9

Author(s):

Marie-Christine Alessi ◽

Christophe Gaudin ◽

Philippe Grosjean ◽

Valérie Martin ◽

Serge Timsit ◽

...

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Clinical Severity ◽

Tissue Type ◽

Stroke Severity ◽

Thrombin Activatable Fibrinolysis Inhibitor ◽

Nihss Score ◽

Multicenter Observational Study ◽

Fibrinolysis Inhibitor ◽

Prospective Longitudinal

Background and Purpose: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA). Methods: In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0-1) and unfavorable (2-6) outcomes. Results: A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003). Conclusion: These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment.

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