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Sex Differences in Prescription Patterns and Medication Adherence to Guideline-Directed Medical Therapy Among Patients With Ischemic Stroke. 缺血性脑卒中患者处方模式和遵医嘱用药的性别差异。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-10-01 DOI: 10.1161/STROKEAHA.124.048058
Hend Mansoor, Daniel Manion, Anna Kucharska-Newton, Chris Delcher, Wei-Hsuan Lo-Ciganic, Gregory A Jicha, Daniela C Moga

Background: Ischemic stroke is a leading cause of death and disability. Society guidelines recommend pharmacotherapies for secondary stroke prevention. However, the role of sex differences in prescription and adherence to guideline-directed medical therapies (GDMT) after ischemic stroke remains understudied. The aim of this study was to examine sex differences in prescription patterns and adherence to GDMT at 1 year after ischemic stroke in a cohort of commercially insured patients.

Methods: Using the Truven Health MarketScan database from 2016 to 2020, we identified patients admitted with ischemic stroke. GDMT was defined as any statin, antihypertensive agents, or oral anticoagulant prescription within 30 days after discharge. Medication adherence was estimated using the proportion of days covered at 1 year. The proportion of days covered <0.80 was used to define nonadherence. A multivariable model adjusting for covariates was performed to identify the factors associated with nonadherence at 1 year. This analysis was restricted to new users of GDMT.

Results: Among 155 220 patients admitted with acute ischemic stroke during the study period, 15 919 met the inclusion criteria. The mean age was 55.7 years, and 8218 (51.7%) were women. Women were less likely to be prescribed statins (58.0% versus 71.8%) and antihypertensive agents (27.7% versus 41.8%). In this subset of patients with atrial flutter/fibrillation, women were also less likely to be prescribed oral anticoagulants (41.2% versus 45.0%). Women were more likely to be nonadherent (ie, proportion of days covered <0.80) to statins (47.3% versus 41.6%; P<0.0001), antihypertensives (33.3% versus 32.2%; P=0.005), and the combination of both (49.6% versus 45.0%; P=0.003). On multivariable analysis, women were likely to be nonadherent to statins and antihypertensive agents at 1 year (odds ratio, 1.23 [95% CI, 1.08-1.41]).

Conclusions: In this real-world analysis of commercially insured patients with ischemic stroke, women were less likely initiated on GDMT within 30 days after discharge. Women were more likely to be nonadherent to statins and antihypertensive agents at 1 year. Future efforts and novel interventions are needed to understand the reasons and minimize these disparities.

背景:缺血性中风是导致死亡和残疾的主要原因。社会指南建议采用药物疗法进行中风二级预防。然而,关于缺血性脑卒中后处方和遵循指南指导的药物疗法(GDMT)的性别差异所起的作用仍未得到充分研究。本研究旨在调查缺血性脑卒中后 1 年时,商业保险患者队列中 GDMT 处方和依从性的性别差异。方法:利用 2016-2020 年的 Truven Health MarketScan 数据库,我们确定了入院的缺血性脑卒中患者。GDMT定义为出院后30天内的任何他汀类药物、降压药和抗凝药处方。用1年的覆盖天数比例(PDC)估算用药依从性。PDC 结果:研究期间收治的 155220 名急性缺血性脑卒中患者中有 15919 人符合纳入标准。平均年龄为 55.7 岁,7701 人(48.3%)为女性。女性较少服用他汀类药物(58.0% 对 71.8%)和降压药(27.7% 对 41.8%)。在这部分心房扑动/心房颤动患者中,女性也较少服用抗凝药(41.2% 对 45.0%)。女性更有可能不依从治疗(即 PDC 结论):在这项针对商业保险缺血性中风患者的真实世界分析中,女性在出院后 30 天内开始接受 GDMT 治疗的可能性较低。女性更有可能在 1 年后不坚持服用他汀类药物和降压药物。今后需要努力采取新的干预措施,以了解这些差异的原因并将其最小化。
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引用次数: 0
High-Risk Embolic Sources on Cardiac Computed Tomography in Patients With Acute Ischemic Stroke: A Case-Control Study. 急性缺血性脑卒中患者心脏计算机断层扫描中的高危栓塞源:病例对照研究。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1161/STROKEAHA.124.048349
Shan Sui Nio, Leon A Rinkel, Joost van Schuppen, Anje M Spijkerboer, Chiel F P Beemsterboer, Valeria Guglielmi, Berto J Bouma, S Matthijs Boekholdt, Nick H J Lobé, Ludo F M Beenen, Henk A Marquering, Charles B L M Majoie, Yvo B W E M Roos, Adrienne van Randen, R Nils Planken, Jonathan M Coutinho

Background: Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS.

Methods: We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020. Cases were patients with a final diagnosis of AIS. Controls were patients with a stroke mimic (SMi). We excluded patients with a transient ischemic attack. Diagnoses were established by an adjudication committee. Cardiac radiologists assessed the presence of structural high-risk sources of cardioembolism according to predefined criteria. We used the Firth penalized likelihood method to perform a logistic regression, adjusted for age, sex, and history of myocardial infarction to determine the association between high-risk embolic sources and AIS. For the primary analysis, we excluded patients with a history of atrial fibrillation. In a secondary analysis, patients with known atrial fibrillation were included.

Results: Of 774 patients, we excluded 167 patients due to no written informed consent or the diagnosis of transient ischemic attack. Of 607 patients, 107 patients had known atrial fibrillation and were excluded from the primary analysis. Of 500 included patients, 375 had AIS (75%, median age 70, 61% male) and 125 SMi (25%, median age 69, 42% male). A high-risk cardioembolic source was found on CT in 32/375 (8.5%) patients with AIS and 0/125 (0%) patients with SMi (adjusted odds ratio, 23.8 [95% CI, 3.3-3032.5]). Cardiac thrombi were the most commonly observed abnormality, present in 23 (6.1%) patients with AIS and 0 (0%) patients with SMi.

Conclusions: A high-risk source of cardioembolism was detected on cardiac CT more frequently in patients with AIS than in patients with SMi. These data substantiate the clinical relevance of cardioembolic sources detected on acute cardiac CT in patients with ischemic stroke.

背景:心脏计算机断层扫描(CT)越来越多地用于寻找急性缺血性卒中(AIS)的心脏栓塞源。我们评估了心脏CT上高危心脏栓塞源与AIS之间的关系。方法:我们使用来自前瞻性队列的数据进行了一项病例对照研究,该队列包括2018年至2020年间在初始卒中成像方案期间接受心脏CT检查的连续疑似卒中成年患者。病例均为最终诊断为AIS的患者。对照组为中风模拟(SMi)患者。我们排除了短暂性脑缺血发作的患者。诊断由一个裁决委员会确定。心脏放射科医生根据预先确定的标准评估心脏栓塞的结构性高危源的存在。我们使用Firth惩罚似然法进行逻辑回归,调整年龄、性别和心肌梗死史,以确定高风险栓塞源与AIS之间的关系。在初步分析中,我们排除了有房颤病史的患者。在二次分析中,已知心房颤动的患者被包括在内。结果:在774例患者中,我们排除了167例患者,因为没有书面知情同意或诊断为短暂性脑缺血发作。在607例患者中,107例患者已知心房颤动,并被排除在初步分析之外。在纳入的500例患者中,375例患有AIS(75%,中位年龄70岁,61%男性),125例重度精神障碍(25%,中位年龄69岁,42%男性)。在32/375 (8.5%)AIS患者和0/125 (0%)SMi患者的CT上发现了高危心脏栓塞源(校正优势比为23.8 [95% CI, 3.3-3032.5])。心脏血栓是最常见的异常,出现在23例(6.1%)AIS患者和0例(0%)SMi患者中。结论:AIS患者在心脏CT上发现心脏栓塞高危源的频率高于重度精神分裂症患者。这些数据证实了在缺血性脑卒中患者的急性心脏CT上检测到心脏栓塞源的临床相关性。
{"title":"High-Risk Embolic Sources on Cardiac Computed Tomography in Patients With Acute Ischemic Stroke: A Case-Control Study.","authors":"Shan Sui Nio, Leon A Rinkel, Joost van Schuppen, Anje M Spijkerboer, Chiel F P Beemsterboer, Valeria Guglielmi, Berto J Bouma, S Matthijs Boekholdt, Nick H J Lobé, Ludo F M Beenen, Henk A Marquering, Charles B L M Majoie, Yvo B W E M Roos, Adrienne van Randen, R Nils Planken, Jonathan M Coutinho","doi":"10.1161/STROKEAHA.124.048349","DOIUrl":"10.1161/STROKEAHA.124.048349","url":null,"abstract":"<p><strong>Background: </strong>Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS.</p><p><strong>Methods: </strong>We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020. Cases were patients with a final diagnosis of AIS. Controls were patients with a stroke mimic (SMi). We excluded patients with a transient ischemic attack. Diagnoses were established by an adjudication committee. Cardiac radiologists assessed the presence of structural high-risk sources of cardioembolism according to predefined criteria. We used the Firth penalized likelihood method to perform a logistic regression, adjusted for age, sex, and history of myocardial infarction to determine the association between high-risk embolic sources and AIS. For the primary analysis, we excluded patients with a history of atrial fibrillation. In a secondary analysis, patients with known atrial fibrillation were included.</p><p><strong>Results: </strong>Of 774 patients, we excluded 167 patients due to no written informed consent or the diagnosis of transient ischemic attack. Of 607 patients, 107 patients had known atrial fibrillation and were excluded from the primary analysis. Of 500 included patients, 375 had AIS (75%, median age 70, 61% male) and 125 SMi (25%, median age 69, 42% male). A high-risk cardioembolic source was found on CT in 32/375 (8.5%) patients with AIS and 0/125 (0%) patients with SMi (adjusted odds ratio, 23.8 [95% CI, 3.3-3032.5]). Cardiac thrombi were the most commonly observed abnormality, present in 23 (6.1%) patients with AIS and 0 (0%) patients with SMi.</p><p><strong>Conclusions: </strong>A high-risk source of cardioembolism was detected on cardiac CT more frequently in patients with AIS than in patients with SMi. These data substantiate the clinical relevance of cardioembolic sources detected on acute cardiac CT in patients with ischemic stroke.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"420-426"},"PeriodicalIF":7.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spontaneous Spinal Cord Infarction in a Young Patient: An Overview of Clinical Features and Management. 一名年轻患者的自发性脊髓梗死:临床特征和治疗综述。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-09 DOI: 10.1161/STROKEAHA.124.049502
Christopher Chornay, Hamza Ahmed, Alexandra Kvernland, Erez Nossek, Sean Michael Kelly
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引用次数: 0
Can a Sniff Help Stratify Your Risk of Stroke?: Predicting Stroke Risk Using Noninvasive, Sensorimotor Biomarkers.
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-27 DOI: 10.1161/STROKEAHA.124.050068
Monica Goss, Sudha Seshadri
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引用次数: 0
Transient Ischemic Attack in Women: Real-World Hospitalization Incidence, Outcomes, and Risk of Hemorrhage and Stroke.
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-27 DOI: 10.1161/STROKEAHA.124.049278
Huanwen Chen, Mihir Khunte, Marco Colasurdo, Shyam Majmundar, Seyedmehdi Payabvash, Seemant Chaturvedi, Ajay Malhotra, Dheeraj Gandhi

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States. Adult patients hospitalized for TIA were included. Annual incidences of TIA hospitalizations for men and women were calculated using the US Census Bureau data. Primary end points were 90-day readmission for ischemic stroke or hemorrhage and compared between men and women. Demographics and comorbidities were captured and used to adjust for confounders using propensity score matching and logistic regression models.

Results: A total of 588 499 patients were identified; 326 794 (55.5%) were women. The estimated annual incidence of TIA hospitalizations was 42.4 (95% CI, 26.0-58.9) per 100 000 women and 36.2 (95% CI, 23.5-48.9) per 100 000 men (relative risk, 1.17 [95% CI, 1.13-1.21]; P<0.001). Overall, women were older, had higher rates of headache and psychiatric comorbidities, and had lower rates of vascular risk factors compared with men. Women were significantly less likely to be readmitted for ischemic stroke (hazard ratio, 0.86 [95% CI, 0.79-0.93]; P<0.001) and more likely to be readmitted for hemorrhage (hazard ratio, 1.12 [95% CI, 1.04-1.20]; P<0.001), with similar rates of antithrombotic use at the time of readmissions (P>0.05). Compared with ischemic stroke, hemorrhage readmissions were significantly associated with lower odds of home discharge (odds ratio, 0.83 [95% CI, 0.76-0.91]; P<0.001) and higher odds of death (odds ratio, 3.01 [95% CI, 2.35-3.87]; P<0.001).

Conclusions: Women have a higher incidence of TIA hospitalizations than men, which may be due to higher rates of nonischemic causes of transient neurological symptoms as evidenced by differences in baseline characteristics and lower rates of subsequent ischemic stroke. Future studies are needed to better characterize transient neurological symptoms in women to avoid excess hospitalizations and unnecessary treatments that may increase hemorrhage risk.

{"title":"Transient Ischemic Attack in Women: Real-World Hospitalization Incidence, Outcomes, and Risk of Hemorrhage and Stroke.","authors":"Huanwen Chen, Mihir Khunte, Marco Colasurdo, Shyam Majmundar, Seyedmehdi Payabvash, Seemant Chaturvedi, Ajay Malhotra, Dheeraj Gandhi","doi":"10.1161/STROKEAHA.124.049278","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049278","url":null,"abstract":"<p><strong>Background: </strong>Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.</p><p><strong>Methods: </strong>This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States. Adult patients hospitalized for TIA were included. Annual incidences of TIA hospitalizations for men and women were calculated using the US Census Bureau data. Primary end points were 90-day readmission for ischemic stroke or hemorrhage and compared between men and women. Demographics and comorbidities were captured and used to adjust for confounders using propensity score matching and logistic regression models.</p><p><strong>Results: </strong>A total of 588 499 patients were identified; 326 794 (55.5%) were women. The estimated annual incidence of TIA hospitalizations was 42.4 (95% CI, 26.0-58.9) per 100 000 women and 36.2 (95% CI, 23.5-48.9) per 100 000 men (relative risk, 1.17 [95% CI, 1.13-1.21]; <i>P</i><0.001). Overall, women were older, had higher rates of headache and psychiatric comorbidities, and had lower rates of vascular risk factors compared with men. Women were significantly less likely to be readmitted for ischemic stroke (hazard ratio, 0.86 [95% CI, 0.79-0.93]; <i>P</i><0.001) and more likely to be readmitted for hemorrhage (hazard ratio, 1.12 [95% CI, 1.04-1.20]; <i>P</i><0.001), with similar rates of antithrombotic use at the time of readmissions (<i>P</i>>0.05). Compared with ischemic stroke, hemorrhage readmissions were significantly associated with lower odds of home discharge (odds ratio, 0.83 [95% CI, 0.76-0.91]; <i>P</i><0.001) and higher odds of death (odds ratio, 3.01 [95% CI, 2.35-3.87]; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>Women have a higher incidence of TIA hospitalizations than men, which may be due to higher rates of nonischemic causes of transient neurological symptoms as evidenced by differences in baseline characteristics and lower rates of subsequent ischemic stroke. Future studies are needed to better characterize transient neurological symptoms in women to avoid excess hospitalizations and unnecessary treatments that may increase hemorrhage risk.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"56 2","pages":"285-293"},"PeriodicalIF":7.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device.
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-27 DOI: 10.1161/STR.0000000000000488
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引用次数: 0
Sex Differences in the Pre- and In-Hospital Setting of Patients With Stroke Are Driven by Higher Age and Stroke Severity. 年龄越大、中风严重程度越高,中风患者住院前和住院期间的性别差异越大。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-10-31 DOI: 10.1161/STROKEAHA.124.048303
Laura P Westphal, Lilian Rüttener, Tim Gasser, Andreas R Luft, Ulrike Held, Susanne Wegener

Background: Sex critically determines stroke pathophysiology and recovery. To reveal potential gaps in stroke care, we analyzed sex-specific differences in the stroke patient hospital admission and treatment process.

Methods: In this single-center retrospective analysis, we screened all patients referred to our stroke center between 2014 and 2020 with suspicion of stroke (n=7112). Patients with different cerebrovascular events and stroke mimics were included. We collected demographic hospitalization and 90-day follow-up data and stratified results according to sex. In a logistic regression analysis for 90-day functional outcome, we estimated the effect of sex corrected for the clinically most relevant confounders.

Results: Of 7102 patients, 56.7% were male and 43.3% female. Women were older (median, 76.3 years; interquartile range (IQR), 64-84, versus 70.7; IQR, 59-79; P<0.001), and lived more often in nursing homes before the event (10.5% versus 3.8%; P<0.001). Among patients with acute ischemic stroke (n=4515), women had more often a large vessel occlusion (38.6% versus 34.8%; P=0.015), a higher stroke severity (National Institutes of Health Stroke Scale score, 4; IQR, 1-12 versus 3; IQR, 1-8; P<0.001), and were treated more often with endovascular treatment (21.4% versus 17.3%; P=0.001). Onset-to-door, onset-to-treatment, and door-to-treatment times were significantly longer in women. A favorable 90-day functional outcome (modified Rankin Scale score 0-2) occurred more often in men (73.9% versus 64.9%; P<0.001). When correcting for confounders in a multivariable logistic regression, age, admission National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale remained highly (P<0.001), large vessel occlusion and arterial hypertension moderately significant predictors for 90-day functional outcome (P<0.05), whereas female sex was not. This could be confirmed when analyzing different patient age groups separately in multivariable logistic regression subgroup analyses. An interaction-term analysis revealed no additional association between age and female sex (OR, 0.99; P=0.815).

Conclusions: Although treatment and outcome parameters seem to be in favor of men, most can be explained by older age, poorer prestroke independence, higher stroke severity, and more large vessel occlusion in women. Sex was not independently associated with worse 90-day functional outcome in women.

背景:性别对中风的病理生理学和康复起着至关重要的作用。为了揭示卒中治疗中的潜在差距,我们分析了卒中患者入院和治疗过程中的性别差异:在这项单中心回顾性分析中,我们筛查了 2014 年至 2020 年期间转诊至卒中中心的所有疑似卒中患者(n=7112)。其中包括不同脑血管事件和卒中模拟患者。我们收集了住院和 90 天随访的人口统计学数据,并根据性别对结果进行了分层。在针对 90 天功能结果的逻辑回归分析中,我们估计了性别对临床上最相关的混杂因素的影响:7102名患者中,56.7%为男性,43.3%为女性。女性年龄更大(中位数为 76.3 岁;四分位间距(IQR)为 64-84 岁;女性为 70.7 岁;IQR 为 59-79 岁;PPP=0.015),中风严重程度更高(美国国立卫生研究院中风量表评分为 4 分;IQR 为 1-12 分;女性为 3 分;IQR 为 1-8 分;PP=0.001)。女性患者从发病到入院、从发病到接受治疗以及从入院到接受治疗的时间明显更长。男性获得良好的90天功能结果(改良Rankin量表评分0-2)的比例更高(73.9%对64.9%;PPPP=0.815):尽管治疗和结果参数似乎对男性更有利,但大部分原因是女性年龄更大、卒中前独立性更差、卒中严重程度更高以及大血管闭塞更多。性别与女性较差的 90 天功能预后无关。
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引用次数: 0
Large-Core Ischemic Stroke Endovascular Treatment: A Science Advisory From the American Heart Association. 大核缺血性卒中血管内治疗:美国心脏协会的科学建议。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-17 DOI: 10.1161/STR.0000000000000481
Nestor R Gonzalez, Pooja Khatri, Gregory W Albers, Oana M Dumitrascu, Mayank Goyal, Anne Leonard, Michael H Lev, Renee Martin, Chi-Hong Tseng

Several trials of endovascular treatment for patients with large-core acute ischemic stroke have been completed. Whereas future stroke clinical guidelines will provide specific recommendations, this advisory aims to summarize the results of these trials, analyze the commonalities and differences among the studies, and discuss the clinical implications of these new results.

针对大核心急性缺血性卒中患者的多项血管内治疗试验已经完成。未来的卒中临床指南将提供具体建议,本咨询旨在总结这些试验的结果,分析研究的共性和差异,并讨论这些新结果的临床意义。
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引用次数: 0
Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial. 机械取栓后辅助动脉内Tenecteplase的安全性:ALLY试点试验。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-08 DOI: 10.1161/STROKEAHA.124.048846
Syed F Zaidi, Alicia C Castonguay, Osama O Zaidat, Ashutosh P Jadhav, Sunil A Sheth, Diogo C Haussen, Thanh N Nguyen, Richard E Burgess, Hisham S Alhajala, Khaled Gharaibeh, Hisham Salahuddin, Rahul Rao, Marion J Oliver, Mouhammad A Jumaa

Background: Recent studies suggest that the use of adjunctive intraarterial alteplase after mechanical thrombectomy (MT) may improve outcomes; however, there are limited data on the use of intraarterial tenecteplase, a newer-generation lytic, in this acute ischemic stroke patient population. Here, we evaluate the use of intraarterial tenecteplase in the ALLY pilot study (Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy).

Methods: ALLY was a prospective, single-center, nonrandomized pilot study assessing the feasibility and safety of intraarterial tenecteplase up to 4.5 mg in acute ischemic stroke-large vessel occlusion MT patients with incomplete recanalization. The primary safety end point was any intracranial hemorrhage and neurological worsening by ≥4 points on the National Institutes of Health Stroke Scale within 24 hours of treatment with intraarterial tenecteplase. A post hoc analysis was performed with a control cohort of MT patients (ALLY MT) not receiving intraarterial tenecteplase.

Results: From April 2022 to July 2023, 218 MTs were performed at ProMedica Hospital (Toledo, OH), of which 20 patients were enrolled in ALLY. The mean age was 66.1±13.8 years, with 35% women. Median baseline National Institutes of Health Stroke Scale scores and Alberta Stroke Program Early CT Scores were 13 (interquartile range, 9-18.8) and 10 (interquartile range, 9-10), respectively. IV thrombolysis was administered in 55%. Most patients presented with middle cerebral artery occlusion (90%). Post-MT modified Treatment in Cerebral Ischemia grade was 2b and 2c in 11 and 9 patients, respectively. Final modified Treatment in Cerebral Ischemia 2b, 2c, and 3 was achieved in 55% (11/20), 35% (7/20), and 10% (2/20), respectively. Any intracranial hemorrhage was observed in 11 patients; however, only 1 patient had symptomatic intracranial hemorrhage. A favorable functional outcome (modified Rankin Scale score, 0-2) at 90 days was achieved in 50%. No difference in intracranial hemorrhage rates was observed between the ALLY and ALLY MT cohorts.

Conclusions: The use of adjunctive intraarterial tenecteplase up to 4.5 mg in patients with acute ischemic stroke with incomplete reperfusion post-MT is feasible and was not associated with increased rates of hemorrhage. Larger, randomized studies are needed to assess the safety and efficacy of intraarterial tenecteplase in this population.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05172934.

背景:最近的研究表明,机械取栓(MT)后使用辅助动脉内阿替普酶可能改善预后;然而,在急性缺血性卒中患者群体中,动脉内使用新一代溶栓剂tenecteplase的数据有限。在此,我们评估了动脉内注射tenecteplase在ALLY试点研究中的应用(机械取栓后辅助动脉内注射tenecteplase)。方法:ALLY是一项前瞻性、单中心、非随机的试点研究,评估4.5 mg动脉内注射tenecteplase治疗急性缺血性卒中-大血管闭塞MT患者不完全再通的可行性和安全性。主要安全性终点是在动脉注射tenecteplase治疗24小时内出现颅内出血和美国国立卫生研究院卒中评分≥4分的神经系统恶化。对一组未接受动脉内注射替尼替普酶的MT患者(ALLY MT)进行了事后分析。结果:2022年4月至2023年7月,在ProMedica医院(托莱多,OH)进行了218例MTs,其中20例患者入组ALLY。平均年龄66.1±13.8岁,女性占35%。美国国立卫生研究院卒中量表评分和阿尔伯塔卒中项目早期CT评分的中位基线分别为13(四分位数范围9-18.8)和10(四分位数范围9-10)。静脉溶栓55%。大多数患者表现为大脑中动脉闭塞(90%)。mt改良治疗后脑缺血分级分别为2b和2c,分别为11例和9例。脑缺血2b、2c和3期的最终改良治疗分别为55%(11/20)、35%(7/20)和10%(2/20)。11例患者颅内出血;但仅有1例患者出现症状性颅内出血。50%的患者在90天获得了良好的功能预后(改进的Rankin量表评分,0-2)。颅内出血发生率在ALLY组和ALLY MT组之间没有观察到差异。结论:在急性缺血性卒中mt后不完全再灌注患者中使用高达4.5 mg的辅助动脉内tenecteplase是可行的,并且与出血发生率增加无关。需要更大规模的随机研究来评估动脉内注射tenecteplase在这一人群中的安全性和有效性。注册:网址:https://www.clinicaltrials.gov;唯一标识符:NCT05172934。
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引用次数: 0
Enhancing Neuron Activity Promotes Functional Recovery by Inhibiting Microglia-Mediated Synapse Elimination After Stroke. 增强神经元活动通过抑制脑卒中后小胶质细胞介导的突触消除促进功能恢复。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-08 DOI: 10.1161/STROKEAHA.124.049265
Hao Sun, Heng Wang, Chaoran Wu, Gang Liu, Meijun He, Hao Zhang, Fengsheng Hou, Hong Liao

Background: Activating glutamatergic neurons in the ipsilesional motor cortex can promote functional recovery after stroke. However, the underlying molecular mechanisms remain unclear. Clarifying key molecular mechanisms involved in recovery could help understand the development of neuromodulation strategies after stroke.

Methods: Adeno-associated virus 2/9-CamKIIa-hM3Dq-mCherry was injected into ipsilesional motor cortex by stereotaxic in the photothrombotic stroke model. Starting from the third day after the stroke, male mice were injected intraperitoneally with clozapine-N-oxide every day to activate excitatory neurons. C1q-blocking antibody and annexin V were used to inhibit C1q and exposed phosphatidylserine (EPS), respectively. The cylinder test and grid-walking test were performed to evaluate functional recovery. The potential molecular mechanisms of excitatory neuronal activation on microglia-mediated synaptic pruning after stroke by immunofluorescence, real-time polymerase chain reaction, Western blotting, and RNA sequencing.

Results: Activating excitatory neurons significantly promoted functional recovery and inhibited microglia-mediated synaptic pruning after stroke. Furthermore, it decreased EPS and C1q levels in synapses. On the contrary, inhibiting excitatory neurons aggravated functional defects, promoted microglia-mediated synaptic pruning, and increased EPS and C1q levels in synapses. Selective blocking of EPS repressed C1q tagging of synapses and microglia-mediated synaptic pruning and improved functional recovery. Meanwhile, blocking EPS markedly rescued synaptic density, and motor function deteriorated by chemogenetic inhibition. In addition, C1q-blocking antibody prevented phosphatidylserine engulfment by microglia.

Conclusions: Together, these data provide mechanistic insight into microglia-mediated synapse pruning after neuronal activation after stroke and identify the role of C1q binding to EPS in stroke treatment during the repair phase.

背景:激活同侧运动皮层的谷氨酸能神经元可以促进脑卒中后的功能恢复。然而,潜在的分子机制尚不清楚。阐明参与恢复的关键分子机制有助于理解脑卒中后神经调节策略的发展。方法:采用立体定向法将腺相关病毒2/9-CamKIIa-hM3Dq-mCherry注射到光血栓性脑卒中模型的同侧运动皮层。从中风后第三天开始,每天向雄性小鼠腹腔注射氯氮平n -氧化物以激活兴奋性神经元。C1q阻断抗体和膜联蛋白V分别抑制C1q和暴露的磷脂酰丝氨酸(EPS)。采用柱体试验和网格行走试验评价功能恢复情况。通过免疫荧光、实时聚合酶链反应、Western blotting和RNA测序研究脑卒中后兴奋性神经元激活对小胶质细胞介导的突触剪枝的潜在分子机制。结果:激活兴奋性神经元可显著促进脑卒中后功能恢复,抑制小胶质细胞介导的突触剪枝。此外,它还能降低突触中EPS和C1q的水平。相反,抑制兴奋性神经元会加重功能缺陷,促进小胶质细胞介导的突触修剪,增加突触中EPS和C1q的水平。选择性阻断EPS可抑制突触的C1q标记和小胶质细胞介导的突触修剪,并改善功能恢复。同时,阻断EPS可明显挽救突触密度,运动功能因化学发生抑制而恶化。此外,c1q阻断抗体可阻止小胶质细胞吞噬磷脂酰丝氨酸。综上所述,这些数据为脑卒中后神经元激活后小胶质细胞介导的突触修剪提供了机制见解,并确定了C1q结合EPS在脑卒中修复期治疗中的作用。
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引用次数: 0
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