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Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes for these patients by considering organizational differences and patient-related factors that influence adherence to target times at the emergency department level. With this in mind, we evaluate the effect of achieving ED time targets from standard protocol and patient-related risk factors on the intravenous (IV) thrombolysis rate in patients with AIS in the therapeutic window. Materials and Methods: For our research, we enrolled people who arrived at the ED with signs of recent AIS with an onset of less than 4.5 h. Initially, 355 patients were included in the study, but through careful screening, only 258 were considered eligible to participate. Of the final group of 258 patients, only 46 received intravenous thrombolysis treatment. Results: In our study, when we are analyzing ED times in patients admitted with stroke symptoms in the therapeutic window, we found statistically significantly decreased ED times for patients that performed IV thrombolysis compared to patients not performing as follows: a median of 100 min in onset-to-ED door time (p < 0.001), a door-to-physician time (ED doctor) of 4 min (p = 0.009), door-to-blood-samples of 5 min (p = 0.026), a door-to-CT time of 15.5 min (p = 0.009), and door-to-CT results of 37 min (p < 0.001). In addition, patients who received intravenous thrombolysis were found to be significantly older (p < 0.001), with lower height and weight (p < 0.001 for both) and lower Glasgow Coma Scale (GCS) scores (9 ± 4.94 vs. 13.85 ± 2.41, p < 0.001). The logistic regression analysis indicated that the onset-to-ED time (p < 0.001) and the door-to-physician time (p = 0.014) for emergency medicine physicians are significant predictors of the likelihood of administering thrombolysis. By analyzing the impact of comorbidities, we observed that dyslipidemia, chronic arterial hypertension, and diabetes mellitus are significant predictive factors for performing IV thrombolysis (the presence of dyslipidemia and diabetes mellitus are predictive factors for performing IV thrombolysis, while the presence of arterial hypertension is not). Conclusions: The ED time targets that significantly influenced IV thrombolysis in our study were the onset-to-ED door time and the time it takes for the ED doctor to assess the AIS patient (door-to-physician time). The IV thrombolysis rate for these patients was 17.83%, lower than expected despite achieving most ED time targets, with the presence of chronic arterial hypertension as a significant predictive patient-related factor for not performing it. Even though our reported hospital's thrombolysis rate is favorable compared to international reports, there is always room for improvement. Based on our study results, it is necessary that new protocols to customized standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Based on our study results, it is necessary that new protocols customize standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. [ABSTRACT FROM AUTHOR]

Nan Chen, Jiadi Gao, Hanshu Zhao, Sihan Liu, Yubing Zhou, Yushuang Liu, Zhongling Zhang, Shanshan Yang Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of ChinaCorrespondence: Shanshan Yang; Zhongling Zhang, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Stree, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China, Tel +86-451-85553681 ; + 86-451-85555918, Fax +86-451-85555918, Email yangshanshan81@163.com; zhangzhongling7@126.comObjective: Stroke is a leading cause of disability and mortality worldwide, posing a significant public health challenge. While treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA) is effective but increases the risk of hemorrhagic transformation (HT). This study aimed to explore the determinants of HT in AIS patients treated with rt-PA and investigate the association between blood glucose levels and HT risk.Methods: We conducted a prospective cohort study at the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2021. Patients with AIS and who received rt-PA within 4.5 hours of symptom onset were included. Demographic, clinical, laboratory, and imaging data were collected.Results: Of the 426 patients, 15% experienced HT post-rt-PA, occurred more frequently in patients with a history of cardiac embolism, higher prethrombolysis NIHSS scores, and elevated fasting blood glucose (FBG) levels. The frequency of HT was higher in non-diabetic patients with FBG levels ≥ 7.0 mmol/L compared to diabetic patients. Elevated blood glucose levels were significantly associated with HT, regardless of diabetes history.Conclusion: The findings suggest importance of precise glycemic control during AIS management to improve patient outcomes, particularly in non-diabetic patients. Future protocols for AIS treatment should incorporate these findings to reduce HT risks. Further large-scale studies are needed to confirm these associations and guide clinical practices.Keywords: Acute ischemic stroke, thrombolytic therapy, rt-PA, hemorrhagic transformation, blood glucose, outcomes

Background and objectives: To minimize stroke-related deaths and maximize the likelihood of cerebral reperfusion, medical professionals developed the "code stroke" emergency protocol, which allows for the prompt evaluation of patients with acute ischemic stroke symptoms in pre-hospital care and the emergency department (ED). This research will outline our experience in implementing the stroke code protocol for acute ischemic stroke patients and its impact on door-to-needle time (DTN) in the ED. Methods: Our study included patients with a "code stroke alert" upon arrival at the emergency department. The final sample of this study consisted of 258 patients eligible for intravenous (IV) thrombolysis with an onset-to-door time < 4.5 h. ED admissions were categorized into two distinct groups: "day shift" (from 8 a.m. to 8 p.m.) (n = 178) and "night shift" (from 8 p.m. to 8 a.m.) (n = 80) groups. Results: An analysis of ED time targets showed an increased median during the day shift for onset-to-ED door time of 310 min (IQR, 190–340 min), for door-to-physician (emergency medicine doctor) time of 5 min (IQR, 3–9 min), for door-to-physician (emergency medicine doctor) time of 5 min (IQR, 3–9 min), and for door-to-physician (neurologist) time of 7 min (IQR, 5–10 min), also during the day shift. During the night shift, an increased median was found for door-to-CT time of 21 min (IQR, 16.75–23 min), for door-to-CT results of 40 min (IQR, 38–43 min), and for door-to-needle time of 57.5 min (IQR, 46.25–60 min). Astonishingly, only 17.83% (n = 46) of these patients received intravenous thrombolysis, and the proportion of patients with thrombolysis was significantly higher during the night shift (p = 0.044). A logistic regression analysis considering the door-to-needle time (minutes) as the dependent variable demonstrated that onset-to-ED time (p < 0.001) and door-to-physician (emergency medicine physicians) time (p = 0.021) are predictors for performing thrombolysis in our study. Conclusions: This study identified higher door-to-CT and door-to-emergency medicine physician times associated with an increased DTN, highlighting further opportunities to improve acute stroke care in the emergency department. Further, door-to-CT and door-to-CT results showed statistically significant increases during the night shift. [ABSTRACT FROM AUTHOR]

Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to the delayed presentation of patients to the emergency department (ED) or the lack of a stroke team/unit in most of the hospitals. Thus, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors influence the administration of rt-PA, we split the general sample (n = 202) into two groups: group No rt-PA (n = 137) and group rt-PA (n = 65). This is based on the performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all samples, we found that the median onset-to-ED door time was 180 min (IQR, 120–217.5 min), door-to-physician time was 4 min (IQR, 3–7 min), door-to-CT time was 52 min (IQR, 48–55 min), and door-in-door-out time was 61 min (IQR, 59–65 min). ED time targets such as door-to-physician time (p = 0.245), door-to-CT time (p = 0.219), door-in-door-out time (p = 0.24), NIHSS at admission to the Neurology department (p = 0.405), or NIHSS after 24 h (p = 0.9) did not have a statistically significant effect on the administration or no rt-PA treatment in patients included in our study. Only the highest door-to-CT time was statistically significantly correlated with the death outcome. Conclusion: In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found. [ABSTRACT FROM AUTHOR]

• Hemorrhagic strokes pose higher risk for seizure at onset than ischemic strokes. • Seizures at stroke onset rare but associated with severe strokes. • Seizures at onset don't affect mortality in patients with iv thrombolysis or thrombectomy. Seizures occurring at the immediate onset of a stroke, abbreviated "seizures at onset" (SaO), pose a diagnostic and therapeutic challenge for physicians. In this study, we report on the current clinical practice in managing stroke patients with SaO from a large tertiary stroke center in Germany. We selected all patients with SaO and acute ischemic or hemorrhagic stroke admitted to the Department of Neurology at the University Hospital of Cologne between 2019 and 01–01 and 2020–12–31. SaO patients were then compared to patients with acute ischemic or hemorrhagic stroke without SaO from the local stroke registry. Further, we compared SaO patients who received intravenous recombinant tissue-type plasminogen activator (rt-PA) and/or mechanical thrombectomy with matched controls. Overall, 54 out of 2312 stroke patients (2.3 %) in the examined period presented with SaO. The most prevalent SaO semiology was focal to bilateral tonic-clonic (42.6 %). SaO was associated with hemorrhagic strokes and higher in-hospital mortality in all stroke patients. The rate of acute stroke therapy was not influenced by the occurrence of SaO. In patients that received acute stroke therapy, patients with SaO had higher scores on the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) at admission, and longer door-to-needle times for the administration of rt-PA, while none of the examined outcome parameters revealed a difference between patients with and without SaO after adjusting for potential confounders. Data show that SaO is rare in stroke patients but associated with more extensive strokes. [ABSTRACT FROM AUTHOR]

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P

目的 评估我国2016—2022年发病6 h内急性缺血性卒中患者静脉溶栓的变化趋势，并比较rt-PA与尿激酶静脉溶栓的院内临床结局差异。 方法 纳入中国卒中中心联盟（Chinese Stroke Center Alliance，CSCA）2016年1月—2022年12月登记的发病6 h内到院的急性缺血性卒中患者555 991例，计算各年份rt-PA静脉溶栓和尿激酶静脉溶栓的比例变化。采用多因素logistic回归法，以rt-PA溶栓为对照，分析尿激酶溶栓对院内脑梗死出血转化、院内死亡及出院时良好神经功能结局（mRS评分0～1分）的影响。 结果 分别有113 521例和30 950例患者进行了rt-PA和尿激酶静脉溶栓，溶栓率分别为20.42%和5.57%。从2016年至2022年，rt-PA静脉溶栓率从11.26%逐年递增至30.19%，而尿激酶静脉溶栓率则始终波动在较低水平。多因素logistic回归分析显示，与rt-PA静脉溶栓相比，尿激酶静脉溶栓患者发生脑梗死后出血转化（OR 0.740，95%CI 0.662～0.827，P＜0.01）和院内死亡的风险较低（OR 0.820，95%CI 0.764～0.881，P＜0.01），但两组患者出院时良好功能结局率无显著差异（OR 0.989，95%CI 0.951～1.028，P=0.57）。 结论 2016—2022年期间，我国发病6 h内到院的急性缺血性卒中患者rt-PA静脉溶栓率呈逐年增长趋势；尿激酶溶栓后发生脑梗死出血转化风险及院内死亡风险可能低于rt-PA静脉溶栓。 Abstract: Objective To investigate the temporal trend of intravenous thrombolysis in patients with acute ischemic stroke (AIS) who arrived within 6 hours after onset from 2016 to 2022 in China, and compare the risks of in-hospital outcomes between rt-PA and urokinase thrombolysis. Methods A total of 555 991 AIS patients who arrived within 6 hours after onset were enrolled in the Chinese Stroke Center Alliance (CSCA) from January 2016 to December 2022. The rates of rt-PA and urokinase intravenous thrombolysis in AIS patients within 6 hours after onset were calculated respectively of each year. Multivariate logistic regression was used to analyze the risks of hemorrhagic transformation, in-hospital death and good functional outcome at discharge (mRS score 0-1) of urokinase thrombolysis group compared with rt-PA group. Results 113 521 and 30 950 patients were treated with rt-PA and urokinase intravenous thrombolytic therapy respectively. The thrombolysis rates of rt-PA and urokinase were 20.42% and 5.57% respectively. From 2016 to 2022, the rt-PA intravenous thrombolysis rate increased from 11.26% to 30.19%, while the urokinase thrombolysis rate fluctuated at a low level. Multivariate logistic regression analysis showed that compared with rt-PA intravenous thrombolytic therapy, patients with urokinase intravenous thrombolytic therapy had a lower risk of hemorrhagic transformation (OR 0.740, 95%CI 0.662-0.827, P

Abstract Background The primary treatment for acute ischemic stroke (AIS) patients is intravenous recombinant tissue plasminogen activator (IV rt-PA). A link between vitamin D insufficiency and worse post-stroke outcomes and more severe strokes was suggested. The present study aimed to assess the prognostic significance of baseline vitamin D levels in AIS patients treated with rt-PA. The present prospective study was conducted 66 patients with acute ischemic stroke within the therapeutic window and treated with rt-PA. Vitamin D levels were assessed using commercial double antibody sandwich enzyme linked immunosorbent assay. The primary study outcome is patient disability of any degree as assessed by the modified Rankin scale (mRS). Results The present study included 66 ischemic stroke patients treated with rt-PA. At baseline, there were 37 patients (56.1%) with low vitamin D levels. Comparison between patients with normal and low vitamin D levels regarding baseline data revealed that the former group were significantly younger and had significantly smaller infarct size patients with normal vitamin D had significantly lower NIHSS at day 2 and day 7. Interestingly, patients with low vitamin D levels had significantly higher frequency of rt-PA related hemorrhage, higher frequency of chest infection, longer hospital stay and higher mRS at 90 days. Multivariate logistic regression analysis identified vitamin D level as significant predictor of functional outcome at 90 days. Conclusions Baseline vitamin D levels is considered a significant predictor of functional outcome in AIS patients treated with rt-PA. It’s also related to infarct size and treatment complications.

Introduction: Stroke is the second leading cause of mortality worldwide. Five percent of all the disability-adjusted life years (DALYs) lost around the world are attributed to stroke. This study aimed to assess the economic burden of acute ischemic stroke (AIS) in Egypt and reveal the benefits of alteplase treatment by measuring the resource use and costs associated with this treatment compared to the standard of care and extrapolate the overall budget impact of alteplase to the local Egyptian setting over a 5-year time horizon from a societal perspective. Methods: A budget impactmodel was developed to estimate the impact of adding alteplase to the current treatment of AIS patients within the Egyptian healthcare setting. The efficacy data for both arms of the model were sourced from a systematic review of the literature. Resource use and cost data were sourced from a retrospective study. Proportions of patients potentially eligible for treatment and the treatment time distributions were estimated from an analysis of the results of this retrospective data collection. A univariate sensitivity analysis was conducted to assess the robustness of the model results. The input parameters varied between plausible extremes based on a review of available evidence. Results: The total annual costs with alteplase treatment [i.e., drug, symptomatic intracerebral hemorrhage (ICH) management, acute hospitalization, and post- hospitalization costs] for the targeted patients from a societal perspective were estimated to be less than the total annual costs without alteplase. This resulted in savings of approximately EGP 37.2 million ($ 1.2 million), EGP 14.2 million ($ 458.06), EGP -33.0 million ($ -1.06 million), EGP -54.0 million ($ -1.74 million), and EGP -89.8 million ($ -2.89 million) for each of the 5 years, respectively. In year 1, more than 2,787 patients (+30.1%) achieved an excellent outcome and <1,204 patients (-22.3%) had a poor outcome when treated with alteplase. The savings in acute hospitalization and post-hospitalization costs o [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

目的 基于机器学习算法对急性缺血性卒中（acute ischemic stroke，AIS）或TIA患者行rt-PA静脉溶栓治疗住院期间脑出血的发生情况进行预测，并探索影响rt-PA溶栓治疗后脑出血发生的危险因素。 方法 纳入中国卒中中心联盟（Chinese Stroke Center Alliance，CSCA）2016年1月—2020年12月登记的被初步诊断为AIS或TIA且接受rt-PA静脉溶栓治疗的患者74 654例，平均年龄为（65.55±12.14）岁，其中，男性患者48 493例（64.96%），住院期间发生脑出血患者2038例（2.73%）。将数据按年份划分为训练集和测试集，即2016—2019年登记患者划分为训练集，2020年登记患者划分为测试集，采用原型选择下采样技术对训练集数据正负样本进行77∶100平衡处理，构建了逻辑回归、极致梯度提升（extreme gradient boosting，XGBoost）、随机森林、梯度提升决策树（gradient boosting decision tree，GBDT）和分类梯度提升（categorical boosting，CatBoost）共5个模型对脑出血结局进行预测，并使用AUC、灵敏度、特异度、Brier评分等指标对模型预测效果进行评价和比较，采用SHAP图对机器学习模型筛选出的特征进行可解释性分析。 结果 XGBoost、GBDT、CatBoost、逻辑回归和随机森林模型的AUC值分别为0.770（95%CI 0.745～0.774）、0.766（95%CI 0.753～0.786）、0.765（95%CI 0.752～0.766）、0.758（95%CI 0.747～0.761）和0.757（95%CI 0.739～0.759），灵敏度分别为0.624（95%CI 0.574～0.672）、0.606（95%CI 0.555～0.655）、0.570（95%CI 0.519～0.620）、0.557（95%CI 0.506～0.607）和0.585（95%CI 0.534～0.635），特异度分别为0.780（95%CI 0.773～0.786）、0.785（95%CI 0.778～0.791）、0.790（95%CI 0.783～0.796）、0.805（95%CI 0.799～0.811）和0.769（95%CI 0.762～0.776），Brier评分分别为0.157、0.154、0.156、0.160和0.161分。通过SHAP图解释结果发现，住院NIHSS评分高、年龄大、空腹血糖水平高、既往心房颤动病史、血小板计数低、发病距溶栓治疗时间窗长、BMI低、就诊时NIHSS评分高等特征为rt-PA溶栓治疗住院期间发生脑出血的危险因素。 结论 基于机器学习构建的预测模型对行rt-PA静脉溶栓治疗的AIS患者住院期间脑出血的发生具有一定预测效果，本研究对未来机器学习技术在脑出血预测领域的应用有一定探索价值。 Abstract: Objective To predict the incidence of cerebral hemorrhage in patients with acute ischemic stroke (AIS) or TIA undergoing intravenous thrombolytic therapy with rt-PA based on machine learning algorithm, and explore the risk factors affecting the incidence of cerebral hemorrhage after rt-PA thrombolytic therapy. Methods A total of 74 654 patients who were initially diagnosed as AIS or TIA and received rt-PA intravenous thrombolytic therapy were enrolled in the Chinese Stroke Center Alliance (CSCA) from January 2016 to December 2020, with an average age of (65.55±12.14) years. Among them, 48 493 were male patients, accounting for 64.96%, and 2038 were cerebral hemorrhage patients during hospitalization, accounting for 2.73%. The data is divided into training sets and test sets by year, that is, the registered patients in 2016—2019 are divided into training sets, and the registered patients in 2020 are divided into test sets. The positive and negative samples of the training set data are 77∶100 balanced using the prototype selection down-sampling technology, and the logistic regression, extreme gradient boosting (XGBoost), random forest, gradient boosting decision tree (GBDT) and categorical boosting (CatBoost) are five models to predict the outcome of intracerebral hemorrhage, and use AUC, sensitivity, specificity, Brier score and other indicators to evaluate and compare the prediction effect of the model, and use SHAP chart to analyze the interpretability of the features screened by the machine learning model. Results The AUC values of XGBoost, GBDT, CatBoost, logistic regression and random forest were 0.770 (95%CI 0.745-0.774), 0.766 (95%CI 0.753-0.786), 0.765 (95%CI 0.752-0.766), 0.758 (95%CI 0.747-0.761) and 0.757 (95%CI 0.739-0.759) respectively, the sensitivity was 0.624 (95%CI 0.574-0.672), 0.606 (95%CI 0.555-0.655), 0.570 (95%CI 0.519-0.620), 0.557 (95%CI 0.506-0.607) and 0.585 (95%CI 0.534-0.635) respectively, the specificity was 0.780 (95%CI 0.773-0.786), 0.785 (95%CI 0.778-0.791), 0.790 (95%CI 0.783-0.796), 0.805 (95%CI 0.799-0.811) and 0.769 (95%CI 0.762-0.776) respectively, and the Brier score was 0.157, 0.154, 0.156, 0.160 and 0.161 respectively. Through the SHAP diagram, we found that the characteristics of high NIHSS score, old age, high fasting blood glucose level, history of atrial fibrillation, low platelet count, long time window between onset and thrombolytic therapy, low BMI, and high NIHSS score at the time of visit were risk factors affecting the incidence of cerebral hemorrhage during the hospitalization of rt-PA thrombolytic therapy. Conclusions The prediction model based on machine learning can predict the occurrence of intracerebral hemorrhage in AIS patients undergoing rt-PA thrombolytic therapy during hospitalization. This study has certain exploration value for the application of machine learning technology in the field of intracerebral hemorrhage prediction in the future.

IntroductionStroke is the second leading cause of mortality worldwide. Five percent of all the disability-adjusted life years (DALYs) lost around the world are attributed to stroke. This study aimed to assess the economic burden of acute ischemic stroke (AIS) in Egypt and reveal the benefits of alteplase treatment by measuring the resource use and costs associated with this treatment compared to the standard of care and extrapolate the overall budget impact of alteplase to the local Egyptian setting over a 5-year time horizon from a societal perspective.MethodsA budget impact model was developed to estimate the impact of adding alteplase to the current treatment of AIS patients within the Egyptian healthcare setting. The efficacy data for both arms of the model were sourced from a systematic review of the literature. Resource use and cost data were sourced from a retrospective study. Proportions of patients potentially eligible for treatment and the treatment time distributions were estimated from an analysis of the results of this retrospective data collection. A univariate sensitivity analysis was conducted to assess the robustness of the model results. The input parameters varied between plausible extremes based on a review of available evidence.ResultsThe total annual costs with alteplase treatment [i.e., drug, symptomatic intracerebral hemorrhage (ICH) management, acute hospitalization, and post-hospitalization costs] for the targeted patients from a societal perspective were estimated to be less than the total annual costs without alteplase. This resulted in savings of approximately EGP 37.2 million ($ 1.2 million), EGP 14.2 million ($ 458.06), EGP −33.0 million ($ −1.06 million), EGP −54.0 million ($ −1.74 million), and EGP −89.8 million ($ −2.89 million) for each of the 5 years, respectively. In year 1, more than 2,787 patients (+30.1%) achieved an excellent outcome and

Background: The primary treatment for acute ischemic stroke (AIS) patients is intravenous recombinant tissue plasminogen activator (IV rt-PA). A link between vitamin D insufficiency and worse post-stroke outcomes and more severe strokes was suggested. The present study aimed to assess the prognostic significance of baseline vitamin D levels in AIS patients treated with rt-PA. The present prospective study was conducted 66 patients with acute ischemic stroke within the therapeutic window and treated with rt-PA. Vitamin D levels were assessed using commercial double antibody sandwich enzyme linked immunosorbent assay. The primary study outcome is patient disability of any degree as assessed by the modified Rankin scale (mRS). Results: The present study included 66 ischemic stroke patients treated with rt-PA. At baseline, there were 37 patients (56.1%) with low vitamin D levels. Comparison between patients with normal and low vitamin D levels regarding baseline data revealed that the former group were significantly younger and had significantly smaller infarct size patients with normal vitamin D had significantly lower NIHSS at day 2 and day 7. Interestingly, patients with low vitamin D levels had significantly higher frequency of rt-PA related hemorrhage, higher frequency of chest infection, longer hospital stay and higher mRS at 90 days. Multivariate logistic regression analysis identified vitamin D level as significant predictor of functional outcome at 90 days. Conclusions: Baseline vitamin D levels is considered a significant predictor of functional outcome in AIS patients treated with rt-PA. It's also related to infarct size and treatment complications. [ABSTRACT FROM AUTHOR]

Several studies highlighted a significant role of specific miRNA as diagnostic and prognostic biomarkers for acute ischemic stroke. The aim of this work was to study micro-RNA 125b-5p level in patients with acute ischemic stroke in relation to stroke etiology, risk factors, severity and outcome. This case–control study was conducted on 40 patients with acute ischemic stroke eligible for receiving rt-PA and 40 age and sex matched healthy controls, Patients were submitted to neurological and radiological assessment. Functional outcome after 3 months was assessed using the modified Rankin Scale (mRS). Plasma micro-RNA 125b-5p levels were measured for both patients and control groups by quantitative real time PCR. MiRNA-125b-5p was extracted from the plasma samples then Real-time quantitative reversed transcription PCR (RT-qPCR) analysis was done. To analyze miRNA-125b-5p expression in plasma, the ∆Cq value of miRNA-125b-5p was calculated by subtracting Cq of miRNA-125b-5p from the average Cq of MiRNA RNU6B. Stroke patients had significantly higher circulating micro-RNA 125b-5p levels in comparison to healthy controls (P value = 0.01). The circulating levels of micro-RNA 125b-5p were positively correlated with stroke severity assessed by National Institutes of Health Stroke Scale (NIHSS) and infarction size. Stroke patients with poor outcome had significantly higher circulating levels of micro-RNA 125b-5p in comparison to those with good outcome (P value ≤ 0.001). The circulating levels of micro-RNA 125b-5p were significantly higher in patients who developed complications after receiving rt-PA (P value ≤ 0.001). Logistic regression model revealed that each unit increase in micro-RNA125b-5p decreased the odds of good outcome by 0.095 (95% CI 0.016–0.58, P value = 0.011). Plasma micro-RNA 125b-5p is significantly elevated is ischemic stroke patients. It is positively correlated with stroke severity and strongly associated with poor outcome and complications after thrombolytic therapy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Spontaneous extensive spinal epidural haematoma poses a unique challenge for the neurosurgeon. Performing extensive laminectomies to remove all of the compressive haematoma can destabilise the patient's spinal column, which may require fixation. This is further complicated in patients with significant coagulopathy. We present a novel use of recombinant tissue plasminogen activator (rt-PA) in a patient with therapeutic coagulopathy, presenting with myelopathy secondary to an acute extensive spinal epidural haematoma. To the best of our knowledge, this is the first case of acute multilevel spinal epidural haematoma that has been successfully evacuated via single level laminectomy and topically applied rt-PA. [ABSTRACT FROM AUTHOR]

Background We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH. Methods We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone. Results In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%. Conclusion Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Stroke is the property of Chinese Journal of Stroke Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundAcute stroke codes may be activated for anisocoria, but how often these codes lead to a final stroke diagnosis or alteplase treatment is unknown. The purpose of this study was to assess the frequency of anisocoria in stroke codes that ultimately resulted in alteplase administration.MethodsWe retrospectively assessed consecutive alteplase-treated patients from a prospectively-collected stroke registry between February 2015 and July 2018. Based on the stroke code exam, patients were categorized as having isolated anisocoria [A+(only)], anisocoria with other findings [A+(other)], or no anisocoria [A-]. Baseline demographics, stroke severity, alteplase time metrics, and outcomes were also collected.ResultsNinety-six patients received alteplase during the study period. Of the 94 who met inclusion criteria, there were 0 cases of A+(only). There were 9 cases of A+(other) (9.6%). A+(other) exhibited higher baseline National Institutes of Health (NIH) Stroke Scale scores compared to A- (17 versus 7; P = .0003), and no additional differences in demographics or alteplase time metrics. Final stroke diagnosis and other outcome measures were no different between A+(other) and A-. Of the A+ patients without pre-existing anisocoria, 5 of 6 (83%) had posterior circulation events or diffuse subarachnoid hemorrhage.ConclusionsIn this exploratory analysis, zero patients with isolated anisocoria received alteplase treatment. Anisocoria as a part of the neurologic presentation occurred in 10% of alteplase patients, and was strongly associated with a posterior circulation event. Therefore, we conclude that anisocoria has a higher likelihood of leading to alteplase treatment when identified in the presence of other neurologic deficits.

Abstract Background C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. Aims We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. Methods The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. Results hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). Conclusions hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients.

Purpose: Thrombus permeability has been related to clot composition and treatment outcomes in stroke patients undergoing reperfusion therapies. The aim of this study was to evaluate whether thrombus perviousness, evaluated by multiphase computed tomography angiography (mCTA), is associated with distal embolization risk. Methods: We interrogated our dataset of acute ischemic stroke (AIS) patients involving the M1 segment of the middle cerebral artery (MCA) who had undergone mechanical thrombectomy, and we calculated thrombus average attenuation measurement (dHU) on non-contrast CT (NCCT) and clot perviousness on mCTA. dHU was calculated as the difference between the thrombus HU average value (tHU) and the HU average value on the contralateral side (cHU), while perviousness was calculated as the difference in mean clot density on mCTA and NCCT both in arterial (Perviousness pre-post-1) and delayed (Perviousness pre-post 2) phases. Results: A total of 100 patients (53 females (53%), mean age 72.74 [± 2.31]) with M1 occlusion were available for analysis. Perviousness, calculated between baseline and arterial phase of mCTA (Perviousness pre-post1), was lower in patients with distal embolization (p = 0.05), revealing an association between reduced perviousness and distal embolization risk. Logistic regression showed that thrombus perviousness calculated on the arterial phase of mCTA (OR, 0.66; 95% CI, 0.44–0.99] (p = 0.04)) and the contact aspiration technique (OR, 0.39; 95% CI, 0.15–1.02] (p = 0.05)) were protecting factors against distal embolization. Conclusion: Our study showed an association between reduced perviousness and distal embolization, suggesting that perviousness evaluation may be a useful neuroimaging biomarker in predicting distal embolization risk during mechanical thrombectomy. [ABSTRACT FROM AUTHOR]

As brain stroke is one of the leading causes of death worldwide, in the current research neuroprotection and performance improvement have been investigated in the Middle cerebral artery occlusion/reperfusion (MCAO/R) animal model treated with exosomes combined with recombinant tissue plasminogen activator (rt-PA). MCAO/R was induced in 25 adult male Wistar rats. Rats received rt-PA (10 mg/kg, i.v.) or exosomes (100 µg/kg) derived from bone marrow mesenchymal stem cells (MSCs). Following the administration of rt-PA alone or in combination with exosomes, a significant increased score of the EBST test was recorded. Also, a decrease in error level of beam test was observed in the treated groups. Cresyl violet staining revealed that the population of dark cells was significantly reduced in all treated groups. The amount of catalase enzyme was significantly increased in all treated groups, especially in the combination therapy group (P<0.05). A considerable increase in superoxide dismutase (SOD) enzyme was observed in the combination therapy group compared to the MCAO/R group (P=0.001). Our conclusion was approved by the Nlrp1 and Nlrp3 downregulation during combination therapy in the MCAO/R model by a reduction in cell death rate. The density of GFAP-positive cells showed a significant decrease in the exosome with or without rt-PA-treated groups compared to the MCAO/R group (P<0.05). Our observation indicated that exosomes, in combination with rt-PA resulted in a noticeable functional recovery, neuronal regeneration, and reduction of neuronal cell death after a 7-day period of the MCAO/R induction. This novel therapeutic strategy probably can provide a promising treatment for patients who suffered from a stroke. [ABSTRACT FROM AUTHOR]

The 2019 year guidelines (American Heart Association / American Stroke Association – AHA/ASA) do not recommend treating recurrent acute ischemic stroke with alteplase in patients who had previous stroke in last 3 months (1,9). According to the European Stroke Organisation`s (ESO) guidelines (year 2021), there is no clear consensus. The risk of reocclusion occurs in 14-34% of patients in whom recanalisation with alteplase has been achieved (1). In this paper we present the case of our 70-year old patient with early stroke recurrence and repeated thrombolytic therapy 9 hours after the first dose of alteplase. [ABSTRACT FROM AUTHOR]

Early neurological deterioration after intravenous thrombolysis (IAT) leads to increased mortality and morbidity in patients with acute ischemic stroke (AIS). This study investigated the correlation between serum Cav-1 and NGB levels and END after IAT and explored their predictive values for poor prognosis of AIS. Totally 210 patients with AIS who underwent IAT within 4.5 h of onset were included and assigned into END group (n = 90) and Non-END group (n = 120). ELISA was used to detect serum Cav-1 and NGB levels before IAT in AIS patients. The prognosis of END patients after 3 months of treatment was evaluated using the modified Rankin Scale. Logistic mul-tifactorial regression was used to analyze independent riskfactors for END and poor prognosis after IAT. ROC curve was used to analyze the predictive effect of Cav-1 and NGB on END and poor prognosis after IAT. The area under the ROC curve was analyzed by MedCalc comparison. Compared with the Non-END group, serum Cav-1 was lower and NGB was higher in the END group. Cav-1 and NGB were independent risk factors for END after IAT. Cav-1 + NGB better predicted END after IAT than Cav-1 or NGB alone. Cav-1 and NGB were independent risk factors for END poor prognosis after IAT. Cav-1 combined with NGB better predicted poor prognosis of END after IAT than Cav-1 or NGB alone. Serum Cav-1 combined with NGB may assist in predicting the risk of END occurrence and poor prognosis after IAT in patients with AIS. [ABSTRACT FROM AUTHOR]

In previous studies, prothrombin time (PT), systemic inflammation response index (SIRI) and systemic immune inflammation Index (SII) levels might be the prognostic factors for patients with ischemic stroke. However, the association between these coagulation and inflammation biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) remains unclear and needs further study. Thus, this study aimed to investigate the relationship between these biomarkers and clinical prognosis after IVT in AIS patients. We included patients at the Hebei general hospital diagnosed with AIS who received standard-dose IVT with rt-PA from September 2017 to August 2022. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included short-term outcome at 24 h and functional outcome at 3 months. We enrolled 281 patients in this study. In total, 16 patients had END within 24 h, and 106 patients had an unfavorable outcome at the 3-month visit. In the multivariate analysis, PT level (OR = 1.833; 95% CI: 1.161-2.893; P = 0.009), SIRI level (OR = 2.166; 95% CI: 1.014-4.629; P = 0.046) and SII level (OR = 1.002; 95% CI: 1.000-1.003; P = 0.021) were independently associated with 3-month poor outcome in AIS patients with IVT. In conclusion, the higher PT, SIRI and SII levels were independently associated with poor prognosis in AIS patients after IVT. Additionally, PT, SIRI and SII all can be novel short-term prognostic biomarkers for AIS patients treated with IVT. [ABSTRACT FROM AUTHOR]

Abstract Introduction Based on demographical trends and the expected worldwide increase in the number of individuals with atrial fibrillation, the rate of patients who are on oral anticoagulation therapy for secondary prevention of stroke rises continuously. Despite correct drug intake and good adherence to the respective medication, recurrent ischemic stroke still occurs in ~ 3% of patients. The question how to deal with such patients with regard to intravenous thrombolysis with rt-PA within the 4.5 h time window is of great relevance for daily clinical routine. However, international guidelines can be considered heterogenous or do even lack recommendations on this topic especially in light of available reversal agents. Therefore, we provide this SOP. Comments Beyond the identification of acute stroke patients on oral anticoagulation therapy, the type of medication, time since last intake, renal function and laboratory exams as well as the availability of reversal agents have to be considered before rt-PA application and potential endovascular therapy. Treatment on a Stroke Unit or Neuro-ICU is certainly recommended in any of those patients. Conclusions This standardized operating procedure was designed to guide stroke physicians through questions on eligibility for rt-PA treatment in patients with acute ischemic stroke who are on approved oral anticoagulation therapy thereby increasing the number of patients benefitting from thrombolysis and minimizing door-to-needle times.

Abstract Background Coronavirus disease 2019 (COVID-19) not only caused a large surge of respiratory infections, it also had a potential association with and increases the risk of stroke. The pandemic has certainly provided new challenges and opportunities in the management of acute ischemic stroke (AIS); however, data regarding outcomes of intravenous tissue plasminogen activator (IV TPA) administration in stroke patients with COVID-19 remains limited. Case presentation Three AIS patients with confirmed COVID-19 treated using IV tPA. One case had excellent outcome, while the other cases showed unfavorable results. The risk–benefit ratio of IV TPA in COVID-19 remains unclear. Conclusion In this article, we discuss the possible explanation behind these different outcomes. Although IV tPA could not cure COVID-19, we suggest that its administration should not be delayed in AIS patients with COVID-19.

Background: The relationship between blood pressure variability and hemorrhagic transformation after recombinant tissue plasminogen activator thrombolysis in patients with acute ischemic stroke is uncertain due to inconsistent methodologies across studies. This study aimed to elucidate the association between 24-h systolic blood pressure extremes post-admission and hemorrhagic transformation while considering the possibility of hemorrhagic transformation occurring beyond the initial monitoring period., Methods: We enrolled patients admitted to The First Affiliated Hospital of Harbin Medical University for ischemic stroke who were treated with intravenous recombinant tissue plasminogen activator within 4.5 h of symptom onset between January 2020 and December 2022. We analyzed the relationships among admission blood pressure, 24-h post-admission recombinant tissue plasminogen activator (mean, maximum, minimum, extreme difference, standard deviation, and coefficient of variation), immediate and 1-h post-thrombolysis blood pressure, and hemorrhagic transformation occurrence within 36 h post-thrombolysis. The potential for delayed hemorrhagic transformation was also considered during the interpretation of the results., Results: Among the 138 patients, 39.1% experienced post-thrombolytic hemorrhagic transformation. Multivariate analysis revealed that hemorrhagic transformation was significantly associated with coronary artery disease, cerebral leukoaraiosis, large cerebral infarction, elevated random glucose levels, and 24-h systolic blood pressure extremes at admission. Specifically, 24-h systolic blood pressure extremes showed a significant positive correlation with hemorrhagic transformation (OR = 1. 042; 95% CI: 1.000-1.086, p  < 0.05)., Conclusion: These findings underscore the importance of establishing robust protocols for continuous blood pressure monitoring and intervention strategies tailored to individual risk profiles. Given that hemorrhagic transformation can occur beyond the initial 36 h, clinicians should maintain vigilance for delayed hemorrhagic transformation, particularly in patients with high recombinant tissue plasminogen activator. Strict control of blood pressure, especially minimizing extremes in systolic blood pressure, is essential to ensure the safety of patients undergoing thrombolysis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: We aimed to examine the prognostic value of syndecan-1 as a marker of glycocalyx injury in patients with acute ischemic stroke (AIS) receiving rt-PA intravenous thrombolysis. Methods: The study included 108 patients with AIS treated with rt-PA intravenous thrombolysis and 47 healthy controls. Patients were divided into unfavorable and favorable prognosis groups based on modified Rankin Scale scores. Univariate and multivariate logistic regression analyses were used to determine risk factors affecting prognosis. Risk prediction models presented as nomograms. The predictive accuracy and clinical value of the new model were also evaluated. Results: Plasma levels of syndecan-1 were significantly higher in patients with AIS than in controls (p < 0.05). Univariate analysis indicated that higher levels of syndecan-1 were more frequent in patients with poor prognosis than in those with good prognosis (t = −4.273, p < 0.001). Syndecan-1 alone and in combination with other factors predicted patient outcomes. After adjusting for confounding factors, syndecan-1 levels remained associated with poor prognosis [odds ratio, 1.024; 95% confidence interval (CI), 1.010–1.038]. The risk model exhibited a good fit, with an area under the receiver operating characteristic curve of 0.935 (95% CI, 0.888–0.981). The categorical net reclassification index (NRI) and continuous NRI values were >0. The integrated discrimination improvement value was 0.111 (95% CI, 0.049–0.174, p < 0.001). Decision curve analysis indicated that the model incorporating syndecan-1 levels was more clinically valuable than the conventional model. Conclusion: Plasma syndecan-1 levels represent a potential marker of prognosis of AIS following intravenous thrombolysis. Adding syndecan-1 to the conventional model may improve risk stratification. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. Aims: We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. Methods: The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. Results: hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). Conclusions: hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Currently, acute ischemic stroke (AIS) is one of the most common and serious diseases in the world and is associated with very high mortality and morbidity even after thrombolysis therapy. This study aims to research the relationship between lactic dehydrogenase (LDH) and prognosis in AIS patients treated with intravenous rtPA. Method: This study (a Multicenter Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke, TRAIS) included 527 AIS patients in 5 cooperative medical institutions in China from January 2018 to February 2021. The primary outcome was major disability and death within 3 months (mRS score of 3–6), and the secondary outcomes were early neurological improvement (ENI), early neurological deterioration (END), moderate-severe cerebral edema (CE), and symptomatic intracranial hemorrhage (sICH). Results: The mean age of the 527 patients was 65.6 ± 11.7 years, and the median baseline NIHSS score was 4 (interquartile range, 2–7). The median serum LDH level was 184 U/L (interquartile range, 163–212 U/L). In total, 287 (54.5%) patients acquired ENI, 68 (13.0%) patients suffered END, 53 (12.1%) patients were observed with moderate-severe CE, and 28 (6.2%) patients showed sICH. Within 3 months, 127 (25.15%) patients experienced the primary outcome and 42 (8.3%) patients died. Serum LDH levels before thrombolysis showed an independent association with the risk of primary outcome [adjusted odds ratio, 3.787; (95% CI, 1.525–9.404); P = 0.014]. When log-transformed LDH increased each standard deviation, the risk of primary outcome was raised by 80.1% (95% CI, 28.9–251.7%). A positive linear dependence between the risk of primary outcome and serum LDH levels (P of linearity = 0.0248, P of non-linearity = 0.8284) was shown in multivariable-adjusted spline regression models. Pre-thrombolysis LDH quartile also provided a conventional risk model and significant improvement of the prediction for clinical outcomes, with a net reclassification improvement index (NRI) = 41.86% (P < 0.001) and integrated discrimination improvement (IDI) = 4.68% (P < 0.001). Conclusions: Elevated serum LDH levels predicted unfavorable clinical outcomes after intravenous thrombolysis in AIS patients. [ABSTRACT FROM AUTHOR]

Ischemic stroke accounts for over 80% of all strokes and is one of the leading causes of mortality and permanent disability worldwide. Intravenous administration of recombinant tissue plasminogen activator (rt-PA) is an approved treatment strategy for acute ischemic stroke of large arteries within 4.5 h of onset, and mechanical thrombectomy can be used for large arteries occlusion up to 24 h after onset. Improving diagnostic work up for acute treatment, reducing onset-to-needle time and urgent radiological access angiographic CT images (angioCT) and Magnetic Resonance Imaging (MRI) are real problems for many healthcare systems, which limits the number of patients with good prognosis in real world compared to the results of randomized controlled trials. The applied endovascular procedures demonstrated high efficacy, but some cellular mechanisms, following reperfusion, are still unknown. Changes in the morphology and function of mitochondria associated with reperfusion and ischemia-reperfusion neuronal death are still understudied research fields. Moreover, future research is needed to elucidate the relationship between continuously refined imaging techniques and the variable structure or physical properties of the clot along with vascular permeability and the pleiotropism of ischemic reperfusion lesions in the penumbra, in order to define targeted preventive procedures promoting long-term health benefits. [ABSTRACT FROM AUTHOR]

Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is a mainstay of acute ischemic stroke treatment but is associated with bleeding complications, especially after prolonged large vessel occlusion. Recently, inhibition of the NLRP3 inflammasome led to preserved blood–brain barrier (BBB) integrity in experimental stroke in vivo. To further address the potential of NLRP3 inflammasome inhibition as adjunct stroke treatment we used immortalized brain derived endothelial cells (bEnd5) as an in vitro model of the BBB. We treated bEnd5 with rt-PA in combination with the NLRP3 specific inhibitor MCC950 or vehicle under normoxic as well as ischemic (OGD) conditions. We found that rt-PA exerted a cytotoxic effect on bEnd5 cells under OGD confirming that rt-PA is harmful to the BBB. This detrimental effect could be significantly reduced by MCC950 treatment. Moreover, under ischemic conditions, the Cell Index—a sensible indicator for a patent BBB—and the protein expression of Zonula occludens 1 stabilized after MCC950 treatment. At the same time, the extent of endothelial cell death and NLRP3 expression decreased. In conclusion, NLRP3 inhibition can protect the BBB from rt-PA-induced damage and thereby potentially increase the narrow time window for safe thrombolysis in stroke. [ABSTRACT FROM AUTHOR]

Background and PurposeCurrently, acute ischemic stroke (AIS) is one of the most common and serious diseases in the world and is associated with very high mortality and morbidity even after thrombolysis therapy. This study aims to research the relationship between lactic dehydrogenase (LDH) and prognosis in AIS patients treated with intravenous rtPA.MethodThis study (a Multicenter Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke, TRAIS) included 527 AIS patients in 5 cooperative medical institutions in China from January 2018 to February 2021. The primary outcome was major disability and death within 3 months (mRS score of 3–6), and the secondary outcomes were early neurological improvement (ENI), early neurological deterioration (END), moderate-severe cerebral edema (CE), and symptomatic intracranial hemorrhage (sICH).ResultsThe mean age of the 527 patients was 65.6 ± 11.7 years, and the median baseline NIHSS score was 4 (interquartile range, 2–7). The median serum LDH level was 184 U/L (interquartile range, 163–212 U/L). In total, 287 (54.5%) patients acquired ENI, 68 (13.0%) patients suffered END, 53 (12.1%) patients were observed with moderate-severe CE, and 28 (6.2%) patients showed sICH. Within 3 months, 127 (25.15%) patients experienced the primary outcome and 42 (8.3%) patients died. Serum LDH levels before thrombolysis showed an independent association with the risk of primary outcome [adjusted odds ratio, 3.787; (95% CI, 1.525–9.404); P = 0.014]. When log-transformed LDH increased each standard deviation, the risk of primary outcome was raised by 80.1% (95% CI, 28.9–251.7%). A positive linear dependence between the risk of primary outcome and serum LDH levels (P of linearity = 0.0248, P of non-linearity = 0.8284) was shown in multivariable-adjusted spline regression models. Pre-thrombolysis LDH quartile also provided a conventional risk model and significant improvement of the prediction for clinical outcomes, with a net reclassification improvement index (NRI) = 41.86% (P < 0.001) and integrated discrimination improvement (IDI) = 4.68% (P < 0.001).ConclusionsElevated serum LDH levels predicted unfavorable clinical outcomes after intravenous thrombolysis in AIS patients.

Introduction: Based on demographical trends and the expected worldwide increase in the number of individuals with atrial fibrillation, the rate of patients who are on oral anticoagulation therapy for secondary prevention of stroke rises continuously. Despite correct drug intake and good adherence to the respective medication, recurrent ischemic stroke still occurs in ~ 3% of patients. The question how to deal with such patients with regard to intravenous thrombolysis with rt-PA within the 4.5 h time window is of great relevance for daily clinical routine. However, international guidelines can be considered heterogenous or do even lack recommendations on this topic especially in light of available reversal agents. Therefore, we provide this SOP. Comments: Beyond the identification of acute stroke patients on oral anticoagulation therapy, the type of medication, time since last intake, renal function and laboratory exams as well as the availability of reversal agents have to be considered before rt-PA application and potential endovascular therapy. Treatment on a Stroke Unit or Neuro-ICU is certainly recommended in any of those patients. Conclusions: This standardized operating procedure was designed to guide stroke physicians through questions on eligibility for rt-PA treatment in patients with acute ischemic stroke who are on approved oral anticoagulation therapy thereby increasing the number of patients benefitting from thrombolysis and minimizing door-to-needle times. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of intravenous alteplase administered 34. 5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown. Patients and Methods: The current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 34.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion. Results: Overall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27–1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80–1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21–2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase. Conclusion: In the 34.5-h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) is the pharmacological treatment of choice in acute thrombotic events. However, a narrow therapeutic window and bleeding complications limit its use. We describe the role of carboxypeptidase inhibitor from potato tuber (PTCI), an inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa), on Glu-plasminogen accumulation and microthrombus dynamics in vivo and demonstrate its influence on rt-PA-mediated thrombolysis. In conjunction with real-time intravital two-photon excitation fluorescence microscopy, we produced and imaged laser-induced microthrombi in the mesenteric venules of Green Fluorescent Protein (GFP)-expressing mice. We examined microthrombus dynamics and thrombolysis patterns in vivo by measuring the changes in the fluorescence intensity of labeled Glu-plasminogen following administration of epsilon aminocaproic acid (EACA), PTCI, and rt-PA. PTCI enhanced Glu-plasminogen accumulation at the core of the thrombus by inhibiting TAFIa, while EACA inhibited this process. Exogenous rt-PA effectively triggered Glu-plasminogen activation within the thrombus and promoted thrombolysis. Administration of PTCI and rt-PA together showed no significant benefit on thrombolysis compared to rt-PA administration alone. However, early-phase systemic administration of PTCI before thrombolytic therapy by rt-PA expedited clot lysis as evidenced by significantly faster time to reach peak Glu-plasminogen fluorescence intensity and shorter time to achieve near-complete clot lysis (P = 0.014 and P = 0.003, respectively). PTCI potentiates rt-PA-mediated thrombolysis when administered early in acute thrombotic events. Further studies are warranted to explore the potential of TAFI inhibitors as adjunct agents in thrombolysis or thromboprophylaxis. [Display omitted] • The TAFIa inhibitor PTCI enhances Glu-plasminogen accumulation within the thrombus. • PTCI is ineffective as a single agent in thrombolysis. • Inhibition of TAFIa by pre-injection of PTCI enhances rt-PA-induced thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) not only caused a large surge of respiratory infections, it also had a potential association with and increases the risk of stroke. The pandemic has certainly provided new challenges and opportunities in the management of acute ischemic stroke (AIS); however, data regarding outcomes of intravenous tissue plasminogen activator (IV TPA) administration in stroke patients with COVID-19 remains limited. Case presentation: Three AIS patients with confirmed COVID-19 treated using IV tPA. One case had excellent outcome, while the other cases showed unfavorable results. The risk–benefit ratio of IV TPA in COVID-19 remains unclear. Conclusion: In this article, we discuss the possible explanation behind these different outcomes. Although IV tPA could not cure COVID-19, we suggest that its administration should not be delayed in AIS patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) is one of the major causes of disability and death worldwide. Currently, intravenous administration of recombinant tissue plasminogen activator (rt-PA), initiated within 4.5 hours after symptom onset, is the standard therapy for AIS. We aimed to predict the 30-day functional outcome of AIS patients who received alteplase in comparison with non- thrombolyzed patients and to evaluate the predictors of the unfavorable outcome after 30 days. Methods: All the data of 80 AIS patients who received rt-PA during the period from 2019 to 2021 were prospectively collected and analyzed. For comparison, 80 patients who received regular treatment, rather than rt-PA within the first 24 h, were selected to match the alteplase group as regards the baseline data and included in the study as a control group. The functional outcome of the thrombolyzed patients after 30 days was evaluated in comparison with controls by using a modified ranking scale. Results: After a 30-day follow-up period, the mortality rate was slightly higher among the rt-PA group (12.5%) in comparison with the control group (10%), however, this difference was not significant. Intracranial hemorrhage (ICH) was significantly higher in the alteplase group than in non- thrombolyzed patients (13.8% vs 3.8%). More patients had a favorable outcome (mRS = 0--2) in the rt-PA group than in the control group (28.7% vs 15%). Age, high baseline blood glucose level, systolic blood pressure, NIHSS score on admission and after 24h, body mass index (BMI) (≥ 30), AF, cardioembolic stroke and occurrence of ICH stroke were significant predictors of functional outcome after IV thrombolysis. Gender, hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, smoking, Ischemic heart disease, previous stroke or transient ischemic attack (TIA) and timing of initiation of thrombolytic therapy had a non-significant effect. Conclusion: After 30-day follow-up period, rt-PA had a significant more increase of favorable functional outcome with increased risk of ICH. Older age, baseline hyperglycemia, high SPB, high NIHSS (either on admission or after 24h), obesity, cardioembolic stroke subtype, history of AF and occurrence of ICH were significant predictors of unfavorable functional outcome after thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Myxoma may cause systemic embolization and frequently presents as ischemic stroke. Case Presentation: There have been debates about whether it is safe to use recombinant tissue plasminogen activator (rt-PA) in patients with cardiac myxoma who referred with ischemic stroke to the hospitalchr('39')s emergency. Results: The patient was a young case of atrial myxoma with initial presentation of acute cerebral infarction symptoms who was treated with intravenous rt-PA with no complications. Conclusion: The case provides an evidence of the efficacy and safety of intravenous rt-PA in cases of cardiac myxoma. However, we cannot always expect thrombolytic therapy to be effective, especially in tumor emboli.

Abstract Background One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial. Methods WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase. Results Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p

Abstract Background The administration of recombinant tissue plasminogen activator (rt-PA) has increased the focus on acute ischemic stroke (AIS) as an emergency condition. The emergency physicians have to rapidly recognize the patients who are candidates for rt-PA and refer them to the specialized stroke team within the proper time window. The knowledge of the emergency physicians about the benefit and the drawbacks of this therapy is crucial and it affects their attitudes towards its use. Objective To apply a survey on the Egyptian emergency physicians aiming to investigate their knowledge about the use rt-PA therapy in AIS. Methodology A self-administered questionnaire was sent to the emergency physicians who are working in three Egyptian governorates. Results Out of 120 emergency physicians, the total knowledge of the study group was good with a score of 7 ± 1.8/11. Most of the participants mentioned the correct answers (over 50%) for all items except for one question regarding the blood glucose control before the use of rt-PA. Significant positive correlation was noted between the knowledge score and the age. Conclusions The surveyed emergency physicians had a good knowledge about the use of rt-PA in AIS, yet, this knowledge is mainly theoretical. Therefore, tutorials, clinical training, and active engagement in the stroke care team are warranted to improve their clinical practice.

BackgroundThe efficacy and safety of intravenous alteplase administered 3–4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown.Patients and MethodsThe current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3–4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion.ResultsOverall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27–1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80–1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21–2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase.ConclusionIn the 3–4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5 h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value˂ 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value = 0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level. [ABSTRACT FROM AUTHOR]

Background: To determine whether it is possible to predict intravenous thrombolytic therapy (IVT) outcome after 3 months in acute ischemic stroke patients who are candidate to receive recombinant tissue plasminogen activator (rt-PA), before rt-PA administration based on their risk factors and some available laboratory results. Methods: We enrolled 118 ischemic stroke patients who were treated with standard dose of Alteplase in our hospital. Baseline characteristics, door-to-needle time (DTN), onset-to-treatment time (OTT), the National Institute Health Stroke Scale (NIHSS), systolic and diastolic blood pressure on admission, history of diabetes, hypertension, dyslipidemia, coronary artery disease (CAD), previous ischemic stroke, atrial fibrillation (AF), laboratory results were retrospectively collected. The modified Rankin Scale (mRS) was recorded after 3 months of admission and patients were divided into good (mRS£ 2) and poor (mRS>2) outcome groups. Chi-square test and t-test were used for categorical and continuous variables, respectively. Predictors for outcome after 3 months were studied by multivariable logistic regression. Results: Good outcome was seen in 60 (51%) patients and poor outcome was seen in 58 (49%) patients. Significant predictors for outcome at 3 months according to multivariable regression analysis were NIHSS score (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.498-0.750; p

Jacek Staszewski,1 Aleksandra Pogoda,1 Kamila Data,1 Klaudia Walczak,1 Maciej Nowocień,2 Emilia Frankowska,2 Adam Stępień1 1Clinic of Neurology, Military Institute of Medicine, Warsaw, Poland; 2Department of Radiology, Military Institute of Medicine, Warsaw, Poland Purpose: The role of biomarkers in the prediction of acute ischemic stroke (AIS) outcome or response to thrombolytic therapy (with recombinant tissue plasminogen activator [rt-PA]) remains limited. The aim of this study was to evaluate whether mean platelet volume (MPV) could predict short-term functional outcome in patients with AIS following rt-PA treatment.Patients and methods: This was a retrospective analysis of 237 AIS patients (mean age 71.04±0.8 years, 50.6% women) consecutively admitted to a tertiary care center between 2011 and 2015.Results: The mean MPV in the cohort was 9.8±0.35 fL (lowest tertile 8.8 fL). Patients in the lowest tertile compared to median and highest tertiles were less often dependent (modified Rankin scale [mRS] ≥3) at admission (87.2% vs 96.1% and 96.1%, respectively, P=0.04) and less often had a poor stroke outcome (mRS 4–6) at discharge (28.2% vs 55.3% and 44.7%, P

Background: Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated.Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio (n = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume.Discussions: This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS.Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR2000038727.