scholarly journals Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
David Malicek ◽  
Ilka Wittig ◽  
Sebastian Luger ◽  
Christian Foerch
Keyword(s):  
Ischemic Stroke ◽  
Pilot Study ◽  
Intracerebral Hemorrhage ◽  
Specific Treatment ◽  
Paraoxonase 1 ◽  
Coagulation Cascade ◽  
Factor Xii ◽  
Blood Biomarker ◽  
Resource Limited ◽  
Significant Difference

Background: A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in patients with stroke. However, in resource-limited settings brain imaging, which is the current diagnostic gold standard for this purpose, is not always available in time. Hence, an easily accessible and broadly applicable blood biomarker-based diagnostic test differing stroke subtypes would be desirable. Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH.Material and Methods: Plasma samples from patients with IS and ICH were drawn during hospitalization and were analyzed by using liquid chromatography/mass spectrometry. Proteins were identified using the human reference proteome database UniProtKB, and label-free quantification (LFQ) data were further analyzed using bioinformatic tools.Results: Plasma specimens of three patients with IS and four patients with ICH with a median National Institute of Health Stroke Scale (NIHSS) of 12 [interquartile range (IQR) 10.5–18.5] as well as serum samples from two healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2 (CPN2), Coagulation factor XII (FXII), Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonic anhydrase 1, Fibulin-1, and Granulins.Discussion: In this exploratory proteomics-based pilot study, nine candidate biomarkers for differentiation of IS and ICH were identified. The proteins belong to the immune system, the coagulation cascade, and the apoptosis system, respectively. Further investigations in larger cohorts of patients with stroke using additional biochemical analysis methods, such as ELISA or Western Blotting are now necessary to validate these markers, and to characterize diagnostic accuracy with regard to the development of a point-of-care-system for use in resource-limited areas.

scholarly journals Next-Generation Antithrombotics in Ischemic Stroke: Preclinical Perspective on ‘Bleeding-Free Antithrombosis’

2012 ◽  
Vol 32 (10) ◽  
pp. 1831-1840 ◽  
Author(s):  
Peter Kraft ◽  
Simon F De Meyer ◽  
Christoph Kleinschnitz
Keyword(s):  
Ischemic Stroke ◽  
Thrombus Formation ◽  
Coagulation Factor ◽  
Coagulation Cascade ◽  
Bleeding Complications ◽  
Factor Xii ◽  
Platelet Inhibitors ◽  
Platelet Surface ◽  
Surface Receptors ◽  
Glycoprotein Vi

The present antithrombotic drugs used to treat or prevent ischemic stroke have significant limitations: either they show only moderate efficacy (platelet inhibitors), or they significantly increase the risk for hemorrhages (thrombolytics, anticoagulants). Although most strokes are caused by thrombotic or embolic vessel occlusions, the pathophysiological role of platelets and coagulation is largely unclear. The introduction of novel transgenic mouse models and specific coagulation inhibitors facilitated a detailed analysis of molecular pathways mediating thrombus formation in models of acute ischemic stroke. Prevention of early platelet adhesion to the damaged vessel wall by blocking platelet surface receptors glycoprotein Ib alpha (GPIb α) or glycoprotein VI (GPVI) protects from stroke without provoking bleeding complications. In addition, downstream signaling of GPIb α and GPVI has a key role in platelet calcium homeostasis and activation. Finally, the intrinsic coagulation cascade, activated by coagulation factor XII (FXII), has only recently been identified as another important mediator of thrombosis in cerebrovascular disease, thereby disproving established concepts. This review summarizes the latest insights into the pathophysiology of thrombus formation in the ischemic brain. Potential clinical merits of novel platelet inhibitors and anticoagulants as powerful and safe tools to combat ischemic stroke are discussed.

scholarly journals A Randomized Controlled Pilot Study of the Triple Stimulation Technique in the Assessment of Electroacupuncture for Motor Function Recovery in Patients with Acute Ischemic Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Feng Tan ◽  
Xuewen Wang ◽  
Hui-qin Li ◽  
Lin Lu ◽  
Ming Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Pilot Study ◽  
Acute Ischemic Stroke ◽  
Motor Function ◽  
Effective Rate ◽  
Function Recovery ◽  
Significant Difference ◽  
Before And After ◽  
Stimulation Technique ◽  
Triple Stimulation Technique

The objective of this pilot study was to objectively assess electroacupuncture for motor function recovery in patients with acute ischemic stroke using the triple-stimulation technique (TST). The patients received either electroacupuncture plus western conventional medication (WCM) (n=32) or single WCM (n=31) for 14 days. The total clinical effective rate was statistically significantly superior in electroacupuncture group to that in WCM group (P<0.01). Fugl-Meyer Assessment Scale (FMA) score, National Institutes of Health Stroke Scale (NIHSS) score, andTSTratiowere statistically more significant in electroacupuncture group than those in WCM group (P<0.01). There was positive correlation betweenTSTratioand NIHS score both before and after treatment (P<0.01) and negative correlation betweenTSTratioand FAM score both before treatment and after treatment (P<0.01). Comparing between the two groups or between pretreatment and posttreatment, adverse events, electrocardiogram, liver function, and kidney function showed no statistically significant difference (P>0.05). In conclusion, electroacupuncture was beneficial for the motor function recovery of patients with acute ischemic stroke and was generally safe. TST can be used for quantitative evaluation of electroacupuncture for motor function recovery in patients with acute ischemic stroke because it can objectively analyze the injury and recovery of corticospinal tract impairments.

scholarly journals Free Fatty Acids in CSF and Neurological Clinical Scores: Prognostic Value for Stroke Severity in ICU

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sayed Gaber ◽  
Sherine Ibrahim ElGazzar ◽  
Mahmoud Qenawi ◽  
Nora Ismail Mohamed Abbas
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Roc Curve ◽  
Stroke Severity ◽  
Factor Xii ◽  
Cutoff Value ◽  
Positive Correlation ◽  
Increased Risk ◽  
Significant Difference ◽  
Infarction Volume

Introduction. Brain ischemia initiated significant increase in FFAs in animal studies. Accumulation of FFA can lead to liberation of inflammatory byproducts that contribute to neuronal death. Increased risk of systemic thromboembolism was seen in animal models after FFA infusion possibly through activation of factor XII by stearic acids. The clinical studies that examined the relation between stroke in humans and CSF biomarkers are infrequent. Aim of Work. We tried to evaluate the potential role of FFAs in CSF in the diagnosis and the prognosis of ICU patients with AIS while comparing the results to traditional neurological scoring systems. Patients and Methods. Our study included 80 patients who were admitted to ICU with acute ischemic stroke (AIS) within 24 hours of the onset of cerebral infarction. CSF samples were obtained at admission. The FFA levels were measured using the sensitive enzyme-based colorimetric method. The NIHSS, GCS, and mRS were evaluated at admission and at 30 days. Univariate and multivariate analysis were used to evaluate the stroke outcome according to FFA levels in CSF. Results. Worsening of the GCS (<7) at 30 days showed a significant correlation with FFA in CSF. The ROC curve showed a cutoff value of 0.27 nmol/µl, sensitivity of 62.9%, and specificity of 72.2%. There was a significant correlation between FFA in CSF and the mRS >2 at 30 days. The ROC curve showed a cutoff value of 0.27 nmol/µl, specificity of 69.2%, and sensitivity of 59.7%. There was a significant correlation between FFA in CSF and the NIHSS ≥ 16 at 30 days. The ROC curve showed a cutoff value of 0.27 nmol/µl, specificity of 72.2%, and sensitivity of 62.9%. Our study subdivided patients according to infarction volume and compared the 2 subgroups with FFA in CSF. We found a significant difference between 2 subgroups. FFA levels showed a positive correlation with infarction volume ≥145 ml. The ROC curve showed a cutoff value of 0.25 nmol/µl, sensitivity of 76.9%, and specificity of 71.4%. Our study showed that FFA in CSF was a significant predictor of all-cause mortality (0.37 + 0.26, P value 0.007). The ROC curve showed a cutoff value of 0.27, specificity of 72.2%, and sensitivity of 62.9%. There was a positive correlation between FFA in CSF and neurological causes of mortality (0.48 + 0.38, P value 0.037). The ROC curve showed a cutoff value of 0.37 nmol/µl, specificity of 76.1%, and sensitivity of 61.5%. Conclusion. FFA in CSF may serve as an independent prognostic biomarker for assessing the prognosis of acute ischemic stroke and the clinical outcome. It might be a useful biomarker for early detection of high-risk patients for poor outcome and hence more aggressive treatment.

scholarly journals Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 2925-2933
Author(s):  
Jianhong Yang ◽  
Yuefei Wu ◽  
Xiang Gao ◽  
Andrew Bivard ◽  
Christopher R. Levi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Propensity Score ◽  
Intracerebral Hemorrhage ◽  
Acute Ischemic Stroke ◽  
Propensity Score Matching ◽  
Death Rate ◽  
Hospital Death ◽  
Endovascular Thrombectomy ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Significant Difference

Background and Purpose: This study aimed to evaluate the treatment effect of intraarterial versus intravenous tirofiban during endovascular thrombectomy in acute ischemic stroke. Methods: This study retrospectively examined 503 patients with acute ischemic stroke with large vessel occlusion who received endovascular thrombectomy within 24 hours of stroke onset. Patients were divided into 3 groups: no tirofiban (n=354), intraarterial tirofiban (n=79), and intravenous tirofiban (n=70). The 3 groups were compared in terms of recanalization rate, symptomatic intracerebral hemorrhage, in-hospital death rate, 3-month death, and 3-month outcomes measured by modified Rankin Scale score (good clinical outcome of 0–2, poor outcome of 5–6). The comparison was statistically assessed by propensity score matching, followed by Freidman rank-sum test and pairwise Wilcoxon signed-rank test with Bonferroni correction. Results: The propensity score matching resulted in 92 matched triplets. Compared with the no-tirofiban group, the intravenous tirofiban group showed significantly increased recanalization (96.7% versus 64.1%, P <0.001), an increased rate of 3-month good outcome (69.5% versus 51.2%, P =0.034), and a lower rate of 3-month poor outcome (12.2% versus 41.4%, P <0.001). There was no significant difference between the tirofiban intravenous and no-tirofiban groups in terms of symptomatic intracerebral hemorrhage (2.2% versus 0%, P =1.000). However, symptomatic intracerebral hemorrhage was significantly increased in the intraarterial-tirofiban group compared with the no-tirofiban group (19.1% versus 0%, P <0.001), with an increased rate of in-hospital death (23.6% versus 0% P <0.001), and increased rate of 3-month death (26.8% versus 11.1%, P =0.021). The intraarterial-tirofiban and no-tirofiban group showed no significant difference in recanalization rate (66.3% versus 64.1%, P =1.000). Conclusions: As an adjunct to endovascular thrombectomy, intravenous tirofiban is associated with high recanalization rate and good outcome, whereas intraarterial tirofiban is associated with high hemorrhagic rate and death rate.

scholarly journals Comparisons of Risk Factors for Intracerebral Hemorrhage versus Ischemic Stroke in Chinese Patients

2017 ◽  
Vol 48 (1-2) ◽  
pp. 72-78 ◽  
Author(s):  
Chung-Fen Tsai ◽  
Jiann-Shing Jeng ◽  
Niall Anderson ◽  
Cathie L.M. Sudlow
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Alcohol Intake ◽  
Stroke Patients ◽  
Stroke Incidence ◽  
Younger Patients ◽  
Significant Difference ◽  
Subgroup Analyses

Background: Chinese populations have a higher stroke incidence, a higher proportion of intracerebral hemorrhage (ICH), and a lower proportion of ischemic stroke (IS) as compared with white populations. The reasons are not fully understood. Methods: To evaluate the differences of major risk factors between ICH and IS in Chinese stroke patients, we analysed acute ICH and IS patients consecutively recruited in National Taiwan University Hospital Stroke Registry from 2006 to 2011. We used multiple logistic regression models to examine the associations of risk factors with ICH vs. IS. Also, we conducted subgroup analyses when a strongly significant interaction was detected. Results: We included a total of 1,373 ICH and 4,953 IS patients. ICH patients were younger than IS patients (mean age 61 vs. 68 years, p < 0.001), but there was no significant difference in gender (males 62 vs. 59%, p = 0.064). A logistic regression model adjusted for age, gender, and other major risk factors showed that both hypertension (OR 2.23, 95% CI 1.74-2.87) and alcohol intake (OR 1.44, 95% CI 1.16-1.77) had significantly stronger associations with ICH than IS, whereas diabetes, atrial fibrillation, ischemic heart disease, hyperlipidemia, smoking, and transient ischemic attack were less associated with ICH than IS. In subgroup analyses, the association of hypertension with ICH vs. IS was more marked in younger patients. Conclusion: Hypertension and alcohol intake are more strongly associated with ICH than IS in Chinese stroke patients, especially in younger patients.

scholarly journals The The Effectiveness of Early Mobilization Time on Balance and Functional Ability after Ischemic Stroke

2019 ◽  
Vol 7 (7) ◽  
pp. 1088-1092
Author(s):  
Umi Budi Rahayu ◽  
Samekto Wibowo ◽  
Ismail Setyopranoto
Keyword(s):  
Randomized Controlled Trial ◽  
Ischemic Stroke ◽  
Functional Ability ◽  
Controlled Trial ◽  
Early Mobilization ◽  
Berg Balance Scale ◽  
Early Mobilisation ◽  
Inclusion Criteria ◽  
Randomized Controlled ◽  
Significant Difference

BACKGROUND: Early mobilisation (EM) after-ischemic stroke is a motor learning intervention aimed to restore nerve cells and to improve balance and functional ability. Unfortunately, the study of when this intervention began has not been widely studied. AIM: On this study was compared the effect of EM started at 24 hours and 48 hours after an ischemic stroke on balance and functional ability. MATERIAL AND METHODS: Randomized controlled trial involving 40 patients on 2 groups meeting predefined inclusion criteria. The levels of balance were measured using the Berg Balance Scale, and the functional ability was measured using the Barthel Index, at 5th and 7th day. RESULTS: A significant difference was observed in both balance (p = 0.038) and functional ability (p = 0.021) obtained on the 7th day of assessment between both groups. A significant difference on the 5th day was observed only in the functional ability (p = 0.002) and not in the balance (p = 0.147), between the groups. CONCLUSION: EM started at 24 hours after the ischemic stroke has been found to have a better impact on balance and functional ability compared to that at 48 hours.

scholarly journals Telemedicine Chronic Viral Hepatitis C Treatment during the Lockdown Period in Romania: A Pilot Study

2021 ◽  
Vol 18 (7) ◽  
pp. 3694
Author(s):  
Irina Paula Doica ◽  
Dan Nicolae Florescu ◽  
Carmen Nicoleta Oancea ◽  
Adina Turcu-Stiolica ◽  
Mihaela-Simona Subtirelu ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Medication Adherence ◽  
Pilot Study ◽  
Multidisciplinary Approach ◽  
Therapy Monitoring ◽  
Antiviral Agents ◽  
Item Score ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Significant Difference

The COVID-19 pandemic is currently delaying the process of chronic hepatitis C (HCV) eradication, since most of the chronic diseases are neglected. Thus, there is a need for alternative programs for HCV therapy implementation and disease monitoring. Our aim was to provide a multidisciplinary approach, so that HCV-infected patients from distant locations may benefit from HCV antivirals during the COVID-19 outbreak and within the lockdown period in Romania. Previously diagnosed HCV patients willing to participate in this telemedicine pilot study were included. Patient characteristics and medical adherence were assessed and compared to the year preceding the pandemic. We proposed a multidisciplinary approach by using a telemedicine program for HCV therapy monitoring. Patients also received a satisfaction questionnaire after delivering the sustained virologic response (SVR) result. A total of 41 patients agreed to participate in this study. The medication adherence was 100% for patients included in the telemedicine group, with a statistically significant difference from the medication adherence of the patients treated in 2019. The satisfaction item score was 4.92 out of 5 and our results (r = −0.94, p < 0.0001) suggested that older patients embraced the telemedicine program less, but with the same success in terms of SVR (100%) and medication adherence (100%). Our pilot study offers the first example of a telemedicine program in Romania for HCV therapeutic management. During the lockdown period, telemedicine has served as a reliable tool and novel alternative for conventional monitoring of patients treated with direct antiviral agents and should be further considered even following the pandemic.

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