Stroke最新文献

{"title":"Intracranial and Peripheral Inflammatory Biomarkers Predict Futile Recanalization after Endovascular Treatment.","authors":"Adrien Ter Schiphorst, Cyril Dargazanli, Julien Labreuche, Francesca Rapido, Marine Blaquière, Christian Jorgensen, Farida Djouad, Emmanuelle Le Bars, Marinette Moynier, Christophe Hirtz, Gregory Gascou, Pierre-Henri Lefevre, Federico Cagnazzo, Thomas Checkouri, François-Louis Collemiche, Quentin Varnier, Lucas Corti, Isabelle Mourand, Thibaut Roux, Xavier Ayrignac, Maarten G Lansberg, Jeremy J Heit, Pierre Seners, Caroline Arquizan, Jean-Claude Baron, Gregory W Albers, Jean-Marc Olivot, Nicola Marchi, Vincent Costalat","doi":"10.1161/STROKEAHA.125.054549","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.054549","url":null,"abstract":"<p><strong>Background: </strong>Futile recanalization (absence of functional independence despite successful endovascular treatment [EVT]) remains a limitation in the treatment of large vessel occlusion stroke. Inflammation has emerged as a key contributor to brain reperfusion injury. Leveraging EVT, we quantified a large panel of immunologic biomarkers in the intracranial and peri-procedural peripheral blood samples and probed their association with futile recanalization.</p><p><strong>Methods: </strong>We conducted a prospective single-center cohort study of patients with anterior-circulation large vessel occlusion, successful EVT (modified Thrombolysis in Cerebral Infarction ≥2b), and no reocclusion. We sampled intracranial blood distal to the thrombus before recanalization and collected peripheral blood immediately before and after EVT, and at 24 hours post-EVT. We measured 37 immune-vascular biomarkers selected a priori, using immunoassays, and tested their associations with futile recanalization (90-day modified Rankin Scale score, 3-6) using rank-based tests with false discovery rate control. Biomarkers meeting a prespecified effect-size threshold (≥0.5) entered multivariable logistic regression models adjusted for age, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, intravenous thrombolysis use, and time from last known well to groin puncture.</p><p><strong>Results: </strong>Among 177 enrolled patients, 139 patients were included (median age, 77 years; 41% women), and 64 (46%) had futile recanalization. Six biomarkers showed at least a medium effect size at ≥1 timepoints: IL (interleukin)-6 (pre-EVT, intracranial, and 24-hour post-EVT), IL-10 (pre-EVT and intracranial), IL-15 (pre-EVT), VEGFR1 (vascular endothelial growth factor receptor 1; pre-EVT and 24-hour post-EVT), VCAM-1 (vascular cell adhesion molecule-1; intracranial and post-EVT), and SAA (serum amyloid A; post-EVT). In adjusted multivariable analyses, futile recanalization remained associated with VCAM-1 intracranially (adjusted odds ratio [aOR], 1.84 [95% CI, 1.11-3.05]) and post-EVT (aOR, 2.08 [95% CI, 1.03-4.19]), IL-10 pre-EVT (aOR, 3.87 [95% CI, 1.58-9.43]) and intracranially (aOR, 4.84 [95% CI, 1.68-13.90]), IL-15 pre-EVT (aOR, 1.60 [95% CI, 1.00-2.53]), and SAA post-EVT (aOR, 7.08 [95% CI, 1.95-25.59]).</p><p><strong>Conclusions: </strong>A core set of immune-vascular mediators measured in blood, both intracranially and peripherally, after EVT predicted futile recanalization. These findings support biomarker-guided risk stratification and motivate trials targeting microvascular inflammation.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843094","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}

{"title":"Expression of Concern for: Ethanol and Normobaric Oxygen Novel Approach in Modulating Pyruvate Dehydrogenase Complex After Severe Transient and Permanent Ischemic Stroke.","authors":"Xiaokun Geng, Omar Elmadhoun, Changya Peng, Xunming Ji, Adam Hafeez, Zongjian Liu, Huishan Du, Jose A Rafols, Yuchuan Ding","doi":"10.1161/STR.0000000000000527","DOIUrl":"https://doi.org/10.1161/STR.0000000000000527","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843114","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}

{"title":"Peripheral Electrical Nerve Stimulation Rescues Spatial Memory Deficits in Vascular Cognitive Impairment Rats by Engaging a Central Cholinergic Circuit.","authors":"Lu Wang, Jing-Wen Yang, Qing-Yong Wang, Yan Cao, Na-Na Yang, Yi-Chun Chai, Cun-Zhi Liu","doi":"10.1161/STROKEAHA.125.053383","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.053383","url":null,"abstract":"<p><strong>Background: </strong>Vascular cognitive impairment (VCI) is a prevalent and heterogeneous condition, both clinically and pathophysiologically, that still lacks approved treatment. Peripheral electrical nerve stimulation (PENS) shows promise for VCI management, yet its underlying neurobiological mechanisms are not well understood.</p><p><strong>Methods: </strong>VCI was induced in rats via permanent bilateral common carotid artery occlusion. Cognitive function was assessed using the Morris water maze, Y-maze, and novel object recognition. Synaptic plasticity was evaluated through long-term potentiation recordings and Golgi staining. The nucleus tractus solitarius (NTS)-medial septum-hippocampus circuit was dissected using fiber photometry recording, immunofluorescence multiplex labeling, in vivo multichannel recordings, anterograde/retrograde tracing, and chemogenetic manipulation.</p><p><strong>Results: </strong>We found that PENS at Zusanli (ST36) acupoint significantly elevated hippocampal acetylcholine levels, enhanced synaptic plasticity, and rescued spatial and nonspatial memory deficits in VCI rats. Chemogenetic activation of cholinergic neurons in the NTS enhanced the cognitive function of VCI rats, whereas chemogenetic inhibition of these neurons counteracted the cognitive benefits of PENS. The NTS sends cholinergic projections to the hippocampal CA1 region through the medial septum. Specific inhibition of NTS^ChAT-medial septum^ChAT-CA1 circuit reversed the enhancement of spatial memory observed in VCI rats treated with PENS, while leaving the nonspatial memory unaffected.</p><p><strong>Conclusions: </strong>Our findings identify the NTS-medial septum-CA1 cholinergic circuit as a critical mechanism mediating PENS-induced reversal of spatial memory deficits in VCI, revealing a novel and spatially selective therapeutic target for VCI.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843119","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}

{"title":"Characteristics of Unsuccessful Recanalization Following Endovascular Thrombectomy: Cohort Study (EVATRISP Collaboration).","authors":"Yoel Schwartzmann, Mirjam R Heldner, Hamza Jubran, Marcel Arnold, Lorenz Grunder, Fatma Shalabi, Tamer Jubeh, Issa Metanis, Annika Nordanstig, Katarina Jood, Alexandros Rentzos, Paul J Nederkoorn, Nabila Wali, Anne van der Meij, Susanne Wegener, Lukas Bastian Otto, Hannah Lea Handelsmann, Patrik Michel, Davide Strambo, Alexander Salerno, Gian Marco De Marchis, Tolga D Dittrich, Sami Curtze, Nicolas Martinez-Majander, Henrik Gensicke, Stefan T Engelter, Valerian Laurin Altersberger, Simon Trüssel, Christian H Nolte, Christoph Riegler, Andrea Zini, Federica Naldi, Guido Bigliardi, Livio Picchetto, João Pedro Marto, José Pedro Costa, Jeremy Molad, Hen Hallevi, Carlo W Cereda, Alessandro Pezzini, Mauro Magoni, Visnja Padjen, Ronen R Leker","doi":"10.1161/STROKEAHA.125.055002","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.055002","url":null,"abstract":"<p><strong>Background: </strong>Successful target vessel recanalization in patients with large vessel occlusion stroke is associated with favorable clinical outcomes. Conversely, unsuccessful recanalization (UR) is associated with higher chances of poor outcomes. UR occurs in up to 30% of endovascular thrombectomy (EVT) procedures, and there are significant knowledge gaps in identifying factors associated with UR.</p><p><strong>Methods: </strong>Prospectively enrolled EVT-treated patients from the EVATRISP registry, which included patients from 18 academic medical centers across Europe between the years 2015 and 2024, were retrospectively studied. Patients had to have data on prestroke and 3-month functional status and recanalization status at the end of EVT. UR was defined as a modified Thrombolysis in Cerebral Infarction score <2b and compared with successful recanalization (modified Thrombolysis in Cerebral Infarction ≥2b). Regression analyses were performed to identify predictors of UR, and a predictive tool was subsequently constructed.</p><p><strong>Results: </strong>Of the 15 549 patients enrolled in EVATRIPS, 10 942 fulfilled entry criteria and were included in the current analysis. Overall, 8000 (73%) achieved successful recanalization, while 2942 (27%) had UR. In multivariate analysis, factors independently associated with higher odds of UR included older age, higher prestroke mRS, wake-up stroke, interhospital transfer for EVT, higher National Institutes of Health Stroke Scale score at presentation, tPA (tissue-type plasminogen activator) administration, and occlusion of the M2 segment of the middle cerebral artery or proximal anterior or posterior cerebral arteries. Dyslipidemia and occlusion of the M1 middle cerebral artery or basilar artery were associated with successful recanalization. UR was associated with poor clinical outcomes, and higher mortality rates. A predictive tool derived from these variables demonstrated limited discriminatory ability (area under the curve, 0.579 [95% CI, 0.567-0.591]; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>UR is frequent among patients undergoing EVT and is associated with poor clinical outcomes. Although several pre-EVT factors were independently associated with UR, accurately predicting which patients will experience UR remains highly challenging. Our findings suggest that all eligible patients should undergo EVT.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843074","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}

{"title":"Improving Readability of Stroke Clinical Trial Consent Forms Using Artificial Intelligence.","authors":"Rohan Arora, Lesli E Skolarus, Robert M Miller, Gaurav Sudhir, Emma L Jacobs, Bijay Mukesh Jeswani, Devin L Brown","doi":"10.1161/STROKEAHA.126.055985","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.055985","url":null,"abstract":"<p><strong>Background: </strong>Informed consent forms (ICFs) for clinical trials are often written above the recommended eighth-grade level. We aimed to compare the readability of original ICFs used for National Institutes of Health-funded stroke-related clinical trials with ICFs edited for readability using artificial intelligence.</p><p><strong>Methods: </strong>Publicly available ICFs associated with National Institutes of Health-funded stroke-related clinical trials were accessed through ClinicalTrials.gov (search period: inception to August 12, 2025). Using ChatGPT-4o, we created a customized Generative Pre-Trained Transformer (GPT) designed to lower the reading level to eighth grade or below while maintaining ICF content. We processed each ICF using this GPT to create edited ICFs. Standard readability metrics, including the Flesch-Kincaid grade level (primary outcome), were compared between original and edited ICFs using paired <i>t</i> tests or the McNemar test (cross-sectional design). We also assessed semantic similarity using the MPNet language model, which produced continuous scores from 0 (no similarity) to 1 (perfect similarity).</p><p><strong>Results: </strong>ICFs were available for 46 stroke trials, including behavioral (n=21), device (n=15), drug (n=5), and other (n=5) intervention types. Mean reading levels were 11.52 for the original and 9.47 for the GPT-edited ICFs using the Flesch-Kincaid grade level (<i>P</i><0.001). Only 1 (2%) of the original ICFs and 18 (39%) of the GPT-edited ICFs had a Flesch-Kincaid reading level at or below eighth grade (<i>P</i><0.001). Both the Simple Measure of Gobbledygook and Gunning Fog Index favored the GPT-edited ICFs by 1 to 2 grade levels. The Flesch Reading Ease score favored the GPT-edited ICFs by about 8 points. The mean similarity score was 0.85 (SD=0.04).</p><p><strong>Conclusions: </strong>GPT-edited ICFs achieved a readability reduction of approximately 2 grade levels compared with the original ICFs while preserving high semantic similarity. Customized GPTs may be a useful tool to improve the readability of clinical trial ICFs.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843132","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}

{"title":"Time-Dependent Efficacy of Thrombolysis Before Thrombectomy: Registry of Stroke Care Quality (RES-Q).","authors":"Robert Mikulik, Geraldo Maranhao Neto, Rupal Sedani, Sandra Thalerová, Natan M Bornstein, Zuzana Gdovinova, Michael D Hill, Adam Kobayashi, Pablo M Lavados, Sheila O Martins, Sandy Middleton, Evija Miglane, Thang Huy Nguyen, Sung-Il Sohn, Nijasri C Suwanwela, P N Sylaja, Georgios Tsivgoulis","doi":"10.1161/STROKEAHA.126.055656","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.055656","url":null,"abstract":"<p><p><b>Background:</b> Randomized evidence suggests that the association of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) may be time-dependent. We evaluated whether treatment timing modifies the association of IVT+EVT versus EVT alone with short-term in-hospital outcomes. <b>Methods:</b> We conducted a multinational observational registry cohort study using RES-Q data (2022-2024) from 38 countries. Among 3,132 eligible anterior-circulation large-vessel occlusion patients treated with EVT, 3,009 comprised the analytic cohort (IVT+EVT or EVT alone). Primary outcome was ordinal modified Rankin Scale (mRS) at discharge; secondary outcomes were mRS 0-2 at discharge and in-hospital survival. Time strata were ≤100, >100-150, >150-255, and >255 minutes. Confounding was addressed with stabilized inverse probability of treatment weighting (IPTW; weights truncated at 10) using a propensity score including arrival mode, admission location/department, vascular risk factors (hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, smoking), imaging type, and baseline NIHSS. For EVT-only patients, onset-to-needle time was predicted only to assign time strata. <b>Results:</b> The mean age was 69.2 years (SD 13.2) and 45.6% were female. Treatment-by-time interaction was significant for ordinal discharge mRS (p=0.002) and mRS 0-2 at discharge (p=0.02). IVT+EVT was associated with better outcomes in the earliest treatment windows: at ≤100 minutes, ordinal mRS odds ratio (OR) 1.99 (95% CI, 1.49-2.63), in-hospital survival OR 1.81 (1.13-2.92), and mRS 0-2 OR 1.76 (1.24-2.51); at >100-150 minutes, ordinal mRS OR 1.58 (1.21-2.06) and mRS 0-2 OR 1.64 (1.16-2.31). Associations were attenuated beyond 150 minutes. <b>Conclusions:</b> In routine practice, early IVT before EVT was most consistently associated with improved discharge outcomes.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842723","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}

{"title":"Core Blood-Brain Barrier Disruption in Patients With Large Vessel Occlusion.","authors":"Richard Leigh, Nefeli Valyraki, Nae-Yuh Wang, Manar Abomulay, Adrien Ter Schiphorst, Adrián Valls Carbó, María Hernández-Pérez, Frédérique Charbonneau, Caroline Arquizan, Anne Wacongne, Denis Sablot, Vincent Costalat, Canan Ozsancak, Clara Cohen, Marco Pasi, Grégoire Boulouis, Nicole Yuen, Jean-Philippe Desilles, Gregory W Albers, Jean Marc Olivot, Pierre Seners","doi":"10.1161/STROKEAHA.126.055955","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.055955","url":null,"abstract":"<p><strong>Background: </strong>Multimodal imaging has expanded treatment for patients with acute ischemic stroke with large vessel occlusion. Blood-brain barrier (BBB) disruption measured in the ischemic core is associated with hemorrhagic transformation. However, the associations between core BBB disruption (cBBBD) and baseline clinical/imaging variables, as well as 3-month outcome, have not been explored.</p><p><strong>Methods: </strong>This is a retrospective multicenter analysis of consecutive anterior circulation patients with acute ischemic stroke with large vessel occlusion, presenting over a 4-year time period, who were transferred from a primary to a comprehensive stroke center for possible endovascular therapy, with magnetic resonance imaging that included perfusion-weighted imaging before transfer. Magnetic resonance imaging scans were processed using RAPID software to generate penumbral imaging variables. Perfusion-weighted images were processed to detect and quantify contrast leakage; cBBBD was calculated as the average of all leaky voxels in the ischemic core. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 3 months. Linear regression was used except for the outcome, which used logistic regression, controlling for age, stroke severity, and baseline functional status.</p><p><strong>Results: </strong>Out of 411 patients transferred for endovascular therapy, 291 were included in this analysis with a median age of 74 years; 49% were female patients. The median National Institutes of Health Stroke Scale score was 13, the mean core volume was 32.3 mL, and the mean cBBBD was 2.1%. 71% of patients underwent endovascular therapy. Admission National Institutes of Health Stroke Scale score (<i>P</i><0.001) and glucose level (<i>P</i>=0.033) were independently correlated with cBBBD. All imaging variables correlated strongly with cBBBD (<i>P</i><0.001). The strongest correlation was 0.50, observed between cBBBD and mismatch ratio (<i>r</i>²=0.254). Increasing cBBBD was independently associated with poor functional outcome (adjusted odds ratio, 1.16 [CI, 1.03-1.32]; <i>P</i>=0.019; n=279), indicating that for every 1% increase in cBBBD, the odds of having a poor functional outcome increase by 16%.</p><p><strong>Conclusions: </strong>In acute ischemic stroke with large vessel occlusion, disruption of the BBB in the core lesion is independently associated with clinical outcome. cBBBD represents a new imaging profile for acute stroke that may help guide treatments.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home-Based Supervised Cardiorespiratory Interval Training Decreases Poststroke Fatigue and Improves Cardiorespiratory Fitness: A Randomized Controlled Trial.","authors":"Anna Bråndal, Maria Svedjebrant, Ylva Nilsagård, Per Wester","doi":"10.1161/STROKEAHA.125.054501","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.054501","url":null,"abstract":"<p><strong>Background: </strong>Poststroke fatigue (PSF) affects nearly half of all stroke survivors and significantly hinders rehabilitation and daily functioning. There is no established treatment. Low cardiorespiratory fitness may contribute to PSF, suggesting aerobic training as a potential intervention.</p><p><strong>Methods: </strong>In this 2-center, randomized, open-label, blinded end point trial, we evaluated a home-based, supervised cardiorespiratory interval training program (HS-CITP) in individuals with PSF (Swedish Fatigue Assessment Scale score ≥28) 1 to 7 months poststroke. Participants were randomized (1:1) to either HS-CITP or usual care with self-directed activity after early supported discharge. The intervention consisted of 35-minute cycling sessions performed 3 times per week at 70% to 80% of maximum heart rate for 8 weeks. The study was powered to detect a 9-point between-group difference on the Swedish Fatigue Assessment Scale. The primary outcome was self-reported fatigue (Swedish Fatigue Assessment Scale score) at 8 weeks (postintervention), and the secondary outcome was peak oxygen uptake (mL/kg per minute) at 8 weeks. Analyses were performed according to the intention-to-treat principle using adjusted between-group comparisons.</p><p><strong>Results: </strong>Forty-five participants were randomized; the mean age was 64 years, and 56% were women. Forty-three participants completed the postintervention assessment (HS-CITP: n=22; control: n=21). Adherence to HS-CITP was 92%, and no adverse events were reported. In adjusted analyses, compared with the control group, HS-CITP significantly reduced fatigue (between-group mean difference -5.35 Swedish Fatigue Assessment Scale score points [95% CI -9.03 to -3.67]; <i>P</i><0.001) and improved cardiorespiratory fitness (+4.48 mL/kg per minute [95% CI, 3.41-5.54]; <i>P</i><0.001). No significant group-by sex interaction was observed.</p><p><strong>Conclusions: </strong>Supervised home-based interval training significantly reduced PSF and improved cardiorespiratory fitness, with good adherence and no safety concerns. These findings support integrating structured aerobic exercise into stroke rehabilitation. Larger, longer-term trials are needed to confirm durability, determine the optimal timing poststroke, and evaluate other exercise modalities.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03458884.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843064","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}

{"title":"Prevalence and Association of Atherosclerosis to Ischemic Stroke in Patients With Atrial Fibrillation on Anticoagulation.","authors":"Alexander W Veltkamp, David Kinzler, Birte Hellwig, Adrian Heeger, Anika Hüsing, Peter U Heuschmann, Jan C Purrucker, Roland Veltkamp","doi":"10.1161/STROKEAHA.126.055284","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.055284","url":null,"abstract":"<p><strong>Background: </strong>Approximately, 20% of ischemic strokes in patients with atrial fibrillation occur despite anticoagulation. These breakthrough strokes are associated with a high risk of recurrence, but underlying mechanisms remain incompletely understood. In particular, the association between carotid atherosclerosis and breakthrough strokes has not been sufficiently assessed.</p><p><strong>Methods: </strong>We analyzed data from the prospective, multicenter, RASUNOA-Prime cohort study (Registry of Acute Stroke Under Novel Oral Anticoagulants-Prime), conducted at 46 German stroke centers between 2015 and 2020. Eligible patients had atrial fibrillation and an ischemic stroke within 24 hours before admission. Of 2737 patients, computed tomography angiography was available for 1464 (53.5%). Patients were grouped according to prestroke anticoagulation with direct oral anticoagulants, vitamin K antagonists, or no oral anticoagulation. Carotid atherosclerosis, including stenosis or occlusion and nonstenosing vulnerable plaques, was assessed by core laboratory computed tomography angiography readings. Carotid arteries served as observational units, with presence of atherosclerosis as binary outcome and laterality of carotid-territory ischemia as explanatory variable in generalized linear mixed models. Laterality of atherosclerosis was assessed as ipsilateral if present on the side of carotid-territory ischemia.</p><p><strong>Results: </strong>Any carotid atherosclerosis was identified in 81% of 1464 patients with available computed tomography angiography. Extracranial carotid stenosis ≥50% or occlusion was present in 17%. Among 792 patients with unilateral carotid-territory ischemia and no stenosis, ipsilateral vulnerable carotid plaques were detected in 34% (no oral anticoagulation 28%, direct oral anticoagulants 38%, vitamin K antagonists 38%), including patients with bilateral plaques, whereas 5% had contralateral vulnerable plaques only. In direct oral anticoagulant-treated patients, odds of ipsilateral vulnerable plaque were significantly higher than in nonanticoagulated patients (odds ratio, 4.4 [95% CI, 1.6-11.8]; <i>P</i>=0.004).</p><p><strong>Conclusions: </strong>Stenosing and nonstenosing carotid atherosclerosis represents a frequent comorbidity in patients with breakthrough strokes, which may contribute to their high risk of recurrence. Longitudinal studies including advanced vascular imaging are needed to clarify the impact of atherosclerosis on stroke recurrence after breakthrough strokes in patients with atrial fibrillation.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02533960.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843234","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}

{"title":"Integrative GWAS and snRNA-seq Reveal a Mesenchymal-Like Endothelial Signature in Moyamoya Disease.","authors":"Yudai Hirano, Satoru Miyawaki, Kyuto Sonehara, Shinichi Namba, Hirotaka Inoue, Yuya Shirai, Hideaki Imai, Hiroki Hongo, Masahiro Shimizu, Hideaki Ono, Yumie Mizoro, Koichi Matsuda, Shotaro Ogawa, Seiei Torazawa, Yu Sakai, Daisuke Sato, Takahiro Tsuchiya, So Hirata, Satoshi Koizumi, Shogo Dofuku, Yuki Shinya, Satoshi Kiyofuji, Daisuke Komura, Akira Teraoka, Hirofumi Nakatomi, Shumpei Ishikawa, Yukinori Okada, Nobuhito Saito","doi":"10.1161/STROKEAHA.125.053747","DOIUrl":"10.1161/STROKEAHA.125.053747","url":null,"abstract":"<p><strong>Background: </strong>Moyamoya disease (MMD) has a strong genetic basis, with the rare <i>RNF213</i> p.Arg4810Lys variant (rs112735431) representing a major risk factor, while the broader genetic architecture and disease-relevant vascular cell types remain incompletely understood.</p><p><strong>Methods: </strong>We conducted a genome-wide association study in Japanese individuals (n=47 656; 401 MMD cases and 47 255 controls). Population-level features at MMD risk loci were examined by regional allele frequency and haplotype analyses. We performed single-nucleus RNA-seq of superficial temporal arteries from patients with MMD (n=3). Cell type-specific enrichment of genome-wide association study signals was assessed using the Single-Cell Disease Relevance Score. Endothelial signatures were validated by integration with publicly available single-cell data sets from controls (n=5) and immunohistochemistry for candidate markers (n=1).</p><p><strong>Results: </strong>Beyond rs112735431, we identified a genome-wide significant signal in the <i>HDAC9-TWIST1</i> region (rs12530920; <i>P</i>=3.3×10^-14; odds ratio, 1.77). Conditional analysis on rs112735431 revealed a protective <i>RNF213</i> missense variant, p.Asp1331Gly (rs8074015; <i>P</i>=3.7×10^-⁹; odds ratio, 0.53), whose minor allele was mutually exclusive with rs112735431-A on haplotypes. Population analysis revealed geographic variation and extended haplotype structure of the rs112735431-A allele in Japan. Single-nucleus RNA-seq identified a mesenchymal-like endothelial cell (MEC) population with selective <i>FN1</i> expression. Genome-wide association study-prioritized disease genes were strongly enriched in MECs. MECs showed mesenchymal pathway activation with a regulatory program distinct from canonical endothelial states. The proportion of MECs was markedly increased in MMD (72% versus 28% in controls), and fibronectin 1 (FN1) expression in endothelial regions was confirmed by immunohistochemistry.</p><p><strong>Conclusions: </strong>Our findings identify a protective <i>RNF213</i> p.Asp1331Gly variant (rs8074015) that is mutually exclusive with the known rs112735431-A allele. Genetic risk converges on an MEC state markedly expanded in MMD.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"1336-1348"},"PeriodicalIF":8.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327012","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}