Journal of Investigative Medicine最新文献

{"title":"Gut Microbiome and Stroke: a Bidirectional Mendelian Randomisation Study in East Asian and European Populations.","authors":"Shiyao Cheng, Hao Zheng, Yuandan Wei, Xingchen Lin, Yuqin Gu, Xinxin Guo, Zhe Fan, Hao Li, Si Cheng, Siyang Liu","doi":"10.1136/svn-2023-002717","DOIUrl":"10.1136/svn-2023-002717","url":null,"abstract":"<p><strong>Background and aims: </strong>Observational studies have implicated the involvement of gut microbiome in stroke development. Conversely, stroke may disrupt the gut microbiome balance, potentially causing systemic infections exacerbated brain infarction. However, the causal relationship remains controversial or unknown. To investigate bidirectional causality and potential ethnic differences, we conducted a bidirectional two-sample Mendelian randomisation (MR) study in both East Asian (EAS) and European (EU) populations.</p><p><strong>Methods: </strong>Leveraging the hitherto largest genome-wide association study (GWAS) summary data from the MiBioGen Consortium (n=18 340, EU) and BGI (n=2524, EAS) for the gut microbiome, stroke GWAS data from the GIGASTROKE Consortium(264 655 EAS and 1 308 460 EU), we conducted bidirectional MR and sensitivity analyses separately for the EAS and EU population.</p><p><strong>Results: </strong>We identified nominally significant associations between 85 gut microbiomes taxa in EAS and 64 gut microbiomes taxa in EU with stroke or its subtypes. Following multiple testing, we observed that genetically determined 1 SD increase in the relative abundance of species <i>Bacteroides pectinophilus</i> decreased the risk of cardioembolic stroke onset by 28% (OR 0.72 (95% CI 0.62 to 0.84); p=4.22e-5), and that genetically determined 1 SD increase in class <i>Negativicutes</i> resulted in a 0.76% risk increase in small vessel stroke in EAS. No significant causal association was identified in the EU population and the reverse MR analysis.</p><p><strong>Conclusion: </strong>Our study revealed subtype-specific and population-specific causal associations between gut microbiome and stroke risk among EAS and EU populations. The identified causality holds promise for developing a new stroke prevention strategy, warrants further mechanistic validation and necessitates clinical trial studies.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"623-630"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724602","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":"Isolated anterior cerebral artery occlusion: an atypical form of moyamoya disease.","authors":"Si-Meng Liu, Gan Gao, Fang-Bin Hao, Shi-Tong Liu, Ri-Miao Yang, Hou-di Zhang, Min-Jie Wang, Zheng-Xing Zou, Dan Yu, Qian Zhang, Qing-Bao Guo, Xiao-Peng Wang, He-Guan Fu, Jing-Jie Li, Cong Han, Lian Duan","doi":"10.1136/svn-2023-002992","DOIUrl":"10.1136/svn-2023-002992","url":null,"abstract":"<p><strong>Background: </strong>The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD.</p><p><strong>Methods: </strong>We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. <i>RNF213</i> p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression.</p><p><strong>Results: </strong>The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent <i>RNF213</i> gene mutation analysis, 90 patients (77.6%) carried the <i>RNF213</i> p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), <i>RNF213</i> p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD.</p><p><strong>Conclusions: </strong>Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with <i>RNF213</i> p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"660-670"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068825","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":"CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II): rationale and design.","authors":"Xin Cheng, Lan Hong, Longting Lin, Leonid Churilov, Yifeng Ling, Yiran Zhang, Lumeng Yang, Mark Parsons, Qiang Dong","doi":"10.1136/svn-2023-002890","DOIUrl":"10.1136/svn-2023-002890","url":null,"abstract":"<p><strong>Background and purpose: </strong>Tenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore the efficacy and safety of TNK in Chinese patients who had an acute ischaemic stroke with large/medium vessel occlusion in an extended time window.</p><p><strong>Methods and design: </strong>Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II) is a multicentre, prospective, block-randomised, open-label, blinded-endpoint, phase IIb study. Eligible patients are 1:1 randomised into two groups: 0.25 mg/kg TNK versus best medical management (excluding TNK). The safety and efficacy of 0.25 mg/kg TNK are assessed through reperfusion status and presence of symptomatic intracranial haemorrhage (sICH).</p><p><strong>Study outcomes: </strong>The primary outcome is major reperfusion without sICH at 24-48 hours after randomisation. Major reperfusion is defined as restoration of blood flow to greater than 50% of the involved ischaemic territory assessed by catheter angiography or repeated perfusion imaging. Secondary outcomes include post-thrombolytic recanalisation, neurological improvements, change in the National Institutes of Health Stroke Scale score, haemorrhagic transformation at 24-48 hours, systematic bleeding at discharge, modified Rankin Scale (mRS) 0-1, mRS 0-2, mRS 5-6, mRS distribution and Barthel index at 90 days.</p><p><strong>Discussion: </strong>CHABLIS-T II will provide important evidence of intravenous thrombolysis with TNK for patients who had an acute stroke in an extended time window.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"708-714"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673374","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":"Rationale and design of ProUrokinase in Mild IsChemic strokE (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial.","authors":"Yunyun Xiong, Manjun Hao, Yuesong Pan, Chunmiao Duan, Xueyan Feng, Hao Li, Na Wu, Liyuan Wang, Xia Meng, Xingquan Zhao, Yongjun Wang","doi":"10.1136/svn-2023-002673","DOIUrl":"10.1136/svn-2023-002673","url":null,"abstract":"<p><strong>Background and purpose: </strong>Recombinant human prourokinase (rhPro-UK) is a new generation of specific plasminogen activator, that is non-inferior to alteplase in acute ischemic stroke. We aimed to investigate the efficacy and safety of rhPro-UK compared with standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset.</p><p><strong>Methods and design: </strong>Prourokinase in mild ischemic stroke is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Patients who had an acute ischemic stroke within 4.5 hours from symptom onset and with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 will be recruited. Patients will be randomly assigned (1:1) to receive intravenous rhPro-UK (35 mg) or standard medical treatment. The follow-up duration will be 90 days. The calculated sample size is 1446.</p><p><strong>Study outcomes: </strong>Primary efficacy outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score ≤ 1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, mRS score ≤ 2 at 90 days, early neurological improvement at 24 hours (a decrease of NIHSS score ≥ 4 points compared with baseline or NIHSS score ≤ 1 point), Barthel index of 75-100 points at 90 days, quality of life at 90 days, and activities of daily living at 90 days. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours, mortality at 90 days, moderate and severe systematic bleeding at 90 days, and adverse events/serious adverse events within 90 days.</p><p><strong>Discussion: </strong>This large phase III randomised clinical trial will answer the question of whether thrombolysis is beneficial for acute mild ischemic stroke, and may provide evidence for rhPro-UK in patients had an acute mild ischemic stroke within 4.5 hours of symptom onset.</p><p><strong>Trial registration number: </strong>NCT05507645.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"715-722"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724605","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":"Recurrent intracerebral haemorrhages as main manifestations in cerebral amyloid angiopathy-related inflammation.","authors":"Ya Su, Yi Dong, Xin Cheng","doi":"10.1136/svn-2024-003100","DOIUrl":"10.1136/svn-2024-003100","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a relatively rare and treatable subtype of CAA. We have herein reported a case of CAA-ri with repeated recurrent lobar haemorrhages within a short time as the main manifestations and effectively treated with immunosuppressive therapy. Our case expanded the clinical spectrum of CAA-ri and indicated that leptomeningeal inflammation might be a trigger and bleeding source for recurrent haemorrhage in CAA.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"738-740"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327292","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":"Development of a deep learning method to identify acute ischaemic stroke lesions on brain CT.","authors":"Alessandro Fontanella, Wenwen Li, Grant Mair, Antreas Antoniou, Eleanor Platt, Paul Armitage, Emanuele Trucco, Joanna M Wardlaw, Amos Storkey","doi":"10.1136/svn-2024-003372","DOIUrl":"10.1136/svn-2024-003372","url":null,"abstract":"<p><strong>Background: </strong>CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed. Machine learning techniques can provide rapid automated CT assessment but are usually developed from annotated images which necessarily limits the size and representation of development data sets. We aimed to develop a deep learning (DL) method using CT brain scans that were labelled but not annotated for the presence of ischaemic lesions.</p><p><strong>Methods: </strong>We designed a convolutional neural network-based DL algorithm to detect ischaemic lesions on CT. Our algorithm was trained using routinely acquired CT brain scans collected for a large multicentre international trial. These scans had previously been labelled by experts for acute and chronic appearances. We explored the impact of ischaemic lesion features, background brain appearances and timing of CT (baseline or 24-48 hour follow-up) on DL performance.</p><p><strong>Results: </strong>From 5772 CT scans of 2347 patients (median age 82), 54% had visible ischaemic lesions according to experts. Our DL method achieved 72% accuracy in detecting ischaemic lesions. Detection was better for larger (80% accuracy) or multiple (87% accuracy for two, 100% for three or more) lesions and with follow-up scans (76% accuracy vs 67% at baseline). Chronic brain conditions reduced accuracy, particularly non-stroke lesions and old stroke lesions (32% and 31% error rates, respectively).</p><p><strong>Conclusion: </strong>DL methods can be designed for ischaemic lesion detection on CT using the vast quantities of routinely collected brain scans without the need for lesion annotation. Ultimately, this should lead to more robust and widely applicable methods.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689301","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":"Dual antiplatelet versus alteplase in anterior and posterior circulation minor stroke.","authors":"Yu Cui, Hui-Sheng Chen","doi":"10.1136/svn-2024-003705","DOIUrl":"10.1136/svn-2024-003705","url":null,"abstract":"<p><strong>Objective: </strong>The Antiplatelet versus R-tPA for Acute Mild Ischaemic Stroke trial has demonstrated the non-inferiority of dual antiplatelet therapy (DAPT) to alteplase in minor non-disabling stroke. This prespecified secondary analysis aimed to investigate whether the treatment effects were similar across stroke territories.</p><p><strong>Methods: </strong>Participants were divided according to stroke territory, which were subdivided into DAPT and alteplase. An excellent functional outcome at 90 days defined as modified Rankin Scale scoring 0-1 was primary outcome. National Institutes of Health Stroke Scale (NIHSS) score change and early neurological improvement measured by a 2-point decline in NIHSS score at 24 hours were secondary outcomes. Symptomatic intracerebral haemorrhage (sICH) and bleeding events were safety outcomes. Primary analyses adjusted unbalanced baseline characteristics between treatments by multivariate logistic regression.</p><p><strong>Results: </strong>A total of 719 patients were included: 566 in anterior circulation stroke (ACS) and 153 in posterior circulation stroke (PCS). Primary outcome was 94.1% in DAPT and 91.7% in alteplase among ACS patients (adjusted risk difference (RD) and 95% CI, 1.5% (-1.5% to 4.6%), p=0.32), while 91.2% in DAPT and 91.8% in alteplase among PCS patients (adjusted RD and 95% CI, -2.1% (-8.5% to 4.4%), p=0.53). Compared with alteplase, DAPT was associated with lower risk of sICH (p=0.03) and bleeding events (p<0.001) in ACS, but only lower risk of bleeding events (p=0.007) in PCS. Additionally, among ACS patients, the alteplase was superior to DAPT in terms of decrease in NIHSS score at 24 hours compared with admission (adjusted geometric mean ratio and 95% CI, -0.09 (-0.16 to -0.03), p=0.005) and early neurological improvement (adjusted RD and 95% CI, -7.2% (-11.6% to -2.7%), p=0.001).</p><p><strong>Conclusion: </strong>Among ischaemic stroke with minor non-disabling symptoms, DAPT was similar with intravenous alteplase regarding long-term functional outcome and better safety regardless of ACS or PCS. The potential benefit of intravenous alteplase regarding early neurological improvement in patients with ACS warrants further investigation.</p><p><strong>Trial registration number: </strong>NCT03661411.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814606","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":"Baseline systolic blood pressure and efficacy of dual antiplatelet in acute ischaemic stroke.","authors":"Yu Cui, Yue Wang, Hui-Sheng Chen","doi":"10.1136/svn-2024-003615","DOIUrl":"10.1136/svn-2024-003615","url":null,"abstract":"<p><strong>Objective: </strong>Systolic blood pressure (SBP) affects the risk of early neurological deterioration (END). This subgroup analysis of Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial aimed to explore whether SBP at admission affected the efficacy of different antiplatelet therapies in preventing END.</p><p><strong>Methods: </strong>Based on the modified intention-to-treat analysis set of the ATAMIS trial, patients were divided into two subgroups according to whether SBP at admission was equal to or higher than 140 mm Hg, which were further subdivided into clopidogrel plus aspirin and aspirin alone treatments according to the randomised assignment. We conducted multivariable regression analyses to detect relationship between SBP at admission and END, as well as efficacy of different antiplatelet therapies in each SBP subgroup. Primary endpoint was END defined as ≥2-point increase in 7-day National Institutes of Health Stroke Scale score. Safety endpoints included intracranial haemorrhage and bleeding events during the trial.</p><p><strong>Results: </strong>This study included 2915 patients. Risk of END raised by 16% as SBP at admission increased by every 10 mm Hg (p<0.001). Clopidogrel plus aspirin resulted in significantly lower risk of END than aspirin alone in patients with SBP≥140 mm Hg (5.5% vs 7.9%; adjusted risk difference (RD) and 95% CI -2.5% (-4.1% to -1.0%)), but not in those with SBP<140 mm Hg (3.4% vs 4.2%; adjusted RD and 95% CI -0.8% (-3.2% to 1.7%)). Efficacy of different antiplatelet therapies and SBP did not show significant interaction (p=0.50). Safety endpoints were similar between treatments in SBP subgroups.</p><p><strong>Conclusion: </strong>The risk of END increases with elevated SBP at admission among patients with acute mild-to-moderate ischaemic stroke who are not suitable for reperfusion treatments. Fewer END occurred following clopidogrel plus aspirin compared with aspirin alone across different SBP levels. The finding should be interpreted cautiously.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796574","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":"Association of <i>APOE</i> genotype with CT markers of cerebral amyloid angiopathy in spontaneous intracerebral haemorrhage.","authors":"Qiong Yang, Xiangzhu Zeng, Lu Tang, Xiaolu Liu, Kailin Xia, Feng Gao, Xu Huang, Nan Li, Dongsheng Fan","doi":"10.1136/svn-2024-003477","DOIUrl":"10.1136/svn-2024-003477","url":null,"abstract":"<p><strong>Background and objective: </strong>We investigated the association of <i>APOE</i> alleles with CT-based cerebral amyloid angiopathy (CAA) markers including subarachnoid extension (SAE) and finger-like projection (FLP).</p><p><strong>Methods: </strong>We included patients with acute primary supratentorial intracerebral haemorrhage (ICH) from a multicentre cohort in China. First, the association of <i>APOE</i> with ICH location (lobar vs non-lobar) was evaluated. Next, the relationships of <i>APOE</i> with SAE, FLP, and the coexistence of the two (SAE+FLP) were evaluated.</p><p><strong>Results: </strong>533 patients with supratentorial ICH were enrolled. Among them were 138 patients with lobar ICH and 395 with non-lobar ICH. Compared with the non-lobar group, <i>APOE</i> ε4 (OR 1.894, 95% CI 1.138 to 3.154, p=0.014) and ε2/ε4 (OR 6.098, 95% CI 1.414 to 26.293, p=0.015) were associated with lobar ICH. With regard to CAA markers, <i>APOE</i> ε2 was associated with SAE (OR 2.109, 95% CI 1.167 to 3.810, p=0.013), ε4 was associated with FLP and SAE+FLP (OR 3.026, 95% CI 1.353 to 6.767, p=0.007; OR 3.514, 95% CI 1.485 to 8.316, p=0.004, respectively) and ε2/ε4 was associated with all three factors (SAH: OR 7.599, 95% CI 1.764 to 32.734, p=0.006; FLP: OR 20.333, 95% CI 3.278 to 126.137, p=0.001; SAE+FLP: OR 30.568, 95% CI 4.460 to 209.503, p<0.001) after adjusting for age, and remained significant after adjusting for age and ICH volume.</p><p><strong>Conclusion: </strong>In patients with spontaneous supratentorial ICH, <i>APOE</i> ε2 and ε4 alleles were associated with SAE and FLP, respectively, suggesting <i>APOE</i> allele-specific effects on CT markers of CAA and their potential mechanisms.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796573","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":"IRIS, a randomised, double-blind, placebo-controlled trial of interleukin-6 receptor inhibition undergoing endovascular treatment in acute anterior circulation ischaemic stroke: study rationale and design.","authors":"Xuehong Chu, Zhengfei Ma, Yifeng Liu, Jun Sun, Ning Wang, Chaoqun Li, Xiangyang Feng, Jianqiao Li, Benxiao Wang, Chen Zhou, Chuanhui Li, Wenbo Zhao, Xunming Ji, Chuanjie Wu","doi":"10.1136/svn-2024-003574","DOIUrl":"https://doi.org/10.1136/svn-2024-003574","url":null,"abstract":"<p><strong>Rationale: </strong>Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke (AIS). Preclinical research indicates that tocilizumab, an interleukin-6 receptor antagonist, can attenuate ischaemia-reperfusion damage by exerting anti-inflammatory and neuroprotective effects.</p><p><strong>Aim: </strong>To determine tocilizumab's efficacy and safety when combined with endovascular thrombectomy (EVT) in patients with acute anterior circulation large vessel occlusion (LVO).</p><p><strong>Sample size estimates: </strong>To determine a 30% decrease in average infarct core volume comparing the intervention and historical control groups (mean increase of 18.7 mL (SD=9.7 mL) post-thrombectomy) via a two-sided test (alpha=0.05, power=80%), accounting for a 10% drop-out rate, we plan to recruit 108 participants.</p><p><strong>Methods and design: </strong>This trial is designed as a randomised, multicentre, double-blind, placebo-controlled trial. Patients will be randomly and evenly allocated to the tocilizumab or placebo groups.</p><p><strong>Study outcomes: </strong>The primary endpoint is the change in infarct core volume between baseline and 72 hours post-treatment. Secondary outcomes include the 90-day modified Rankin scale score (0-2, indicating functional independence). The key safety endpoints include 90-day mortality and symptomatic intracerebral haemorrhage within 72 hours after EVT.</p><p><strong>Discussion: </strong>Administering tocilizumab within 24 hours of stroke as an adjunct to EVT may effectively reduce the infarct core volume for patients experiencing AIS with anterior circulation LVO, potentially improving functional outcomes in these patients.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751872","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}