Journal of Investigative Medicine最新文献

{"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}

{"title":"Improved functional outcome for stroke patients with low ASPECTS score large core infarctions: 1-year follow-up of three randomised trials.","authors":"Yang Zhang, David Wang, Yi Sui","doi":"10.1136/svn-2024-003868","DOIUrl":"https://doi.org/10.1136/svn-2024-003868","url":null,"abstract":"","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":"142755629","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":"Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial.","authors":"Xiaochuan Huo, Gang Luo, Dapeng Sun, Thanh Nguyen, Mohamad Abdalkader, Wenhuo Chen, Xiaoxi Yao, Guangxiong Yuan, Tingyu Yi, Hongxin Han, Yuesong Pan, Tudor G Jovin, David S Liebeskind, Liping Liu, Xingquan Zhao, Zeguang Ren, Yilong Wang, Yongjun Wang, Bernard Yan, Zhongrong Miao","doi":"10.1136/svn-2024-003318","DOIUrl":"10.1136/svn-2024-003318","url":null,"abstract":"<p><strong>Background: </strong>Despite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3.</p><p><strong>Methods: </strong>ANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio.</p><p><strong>Results: </strong>The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0-1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0-2, mRS 0-3, all-cause mortality and any intracranial haemorrhage.</p><p><strong>Conclusion: </strong>In patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes.</p><p><strong>Trial registration number: </strong>NCT05624190.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367097","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":"Clinical outcomes of endovascular interventions for cerebral venous thrombosis in Japan: a nationwide retrospective study.","authors":"Atsushi Senda, Hiroshi Suginaka, Koji Morishita, Kiyohide Fushimi","doi":"10.1136/svn-2024-003639","DOIUrl":"https://doi.org/10.1136/svn-2024-003639","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebral venous thrombosis (CVT) is a rare but serious disease. Despite anticoagulation being the cornerstone therapy, some patients experience worsening disease, necessitating alternative treatment. Endovascular treatment is an anticipated option with an uncertain clinical relevance. The aim of this study was to assess the clinical effects and efficacy of endovascular therapy and identify patient populations that may benefit from treatment.</p><p><strong>Patients and methods: </strong>This retrospective study examined patient data from April 2014 to March 2022 that were extracted from a nationwide Japanese Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes included modified Rankin Scale (mRS) scores and post-hospitalisation complications of cerebral infarction and intracranial haemorrhage. Severity was adjusted using a generalised linear mixed model, and propensity-score matching was employed to compare outcomes between treatment groups.</p><p><strong>Results: </strong>The study included 2901 patients; 240 patients in the endovascular treatment group were matched with 240 patients in the standard treatment group. After adjusting for background factors, endovascular treatment did not improve in-hospital mortality (adjusted OR 1.45; 95% CI 0.74 to 2.16) or the mRS score (adjusted OR 0.89, 95% CI 0.56 to 1.23). No subpopulations that could benefit from endovascular treatment were identified. Post-hospitalisation cerebral infarction and intracranial haemorrhage did not increase with endovascular treatment (0.8% in the endovascular treatment group vs 1.2% in the standard treatment group).</p><p><strong>Conclusion: </strong>Endovascular treatment showed no significant benefit for patients with CVT, indicating that treatment guidelines need to be refined. Our findings can guide clinical decisions and suggest the necessity of further research on potential benefits in specific subpopulations.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689299","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":"0.23-Tesla MRI to differentiate between ischaemic and haemorrhagic strokes within 24 hours of onset: a combined experimental-clinical study.","authors":"Xuewei Xie, Qianmei Jiang, Yue Suo, Chong Han, Zhaobin Wang, Zhe Zhang, Ning Wang, Yihuai Wang, Chunguang Zhang, Bingshan Xue, Tao Liu, David Wang, Jing Jing, Yongjun Wang","doi":"10.1136/svn-2024-003592","DOIUrl":"https://doi.org/10.1136/svn-2024-003592","url":null,"abstract":"<p><strong>Background and purpose: </strong>The low-field MRI is a promising tool to accurately diagnose strokes. We here report our study on the accuracy of a 0.23-Tesla (0.23-T) MRI using the haematoma enhanced inversion recovery (HEIR) sequence to detect acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) within 24 hours of symptom onset.</p><p><strong>Methods: </strong>A novel HEIR sequence based on fluid-attenuated inversion recovery T1-weighted, with a scanning time of 1 min and 17 s, was developed using an ICH and AIS pig model on a 0.23-T MRI. Images of the pig model were obtained hourly for 24 hours in order to monitor value changes on T1/T2 and verify the differential diagnosis of AIS and ICH. Then, 30 patients with AIS and 30 patients with ICH with confirmed diagnoses by 3T-MRI/CT were included. Diagnostic criteria on a 0.23-T MRI for ICH was the hyperintensity signal on both the diffusion-weighted imaging (DWI) and HEIR sequence, while for AIS was the hyperintensity on DWI and isointensity on the HEIR sequence. Two blinded raters independently assessed the images obtained by the 0.23-T MRI for the presence of ICH/AIS.</p><p><strong>Results: </strong>In the pig model, setting the inversion time to 800 ms enabled clear differentiation of ICH from brain parenchymal tissue and AIS. In real patients, a correct 0.23-T MRI diagnosis of either an AIS or ICH was made in all 60 patients within 24 hours of symptom onset (100% overall accuracy). No adverse events occurred.</p><p><strong>Conclusions: </strong>The 0.23-T MRI may have the potential to differentiate cerebral haemorrhage from cerebral infarction with both speed and accuracy, making brain MRI scans easier, faster and cheaper. It might be possible to improve the screening imaging process for strokes in the emergency room. Further multicentre studies are needed to validate our findings.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689297","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":"Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study.","authors":"Ye Liu, Guozhi Lu, Dan Li, Guang Wu, Xiaoyu Zhou, Rongbo Qu, Yongren Fang, ZhiJiao He, Anqi Zhang, Lan Hong, Kun Fang, Xin Cheng, Qiang Dong","doi":"10.1136/svn-2024-003381","DOIUrl":"https://doi.org/10.1136/svn-2024-003381","url":null,"abstract":"<p><strong>Background and aims: </strong>Tenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and effectiveness in China.</p><p><strong>Methods: </strong>We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke (AIS) within 4.5 hours of onset between 1 March 2019 and 1 October 2023, from 18 stroke centres in China. Using propensity score matching (PSM), TNK-treated patients were matched 1:1 with alteplase-treated patients. The primary outcome was the rate of symptomatic intracranial haemorrhage (sICH) within 72 hours post-thrombolysis. Secondary outcomes comprised the rate of parenchymal haemorrhage type 2, any intracranial haemorrhage, any systematic bleeding and mortality at 90 days, as well as 24-hour National Institutes of Health Stroke Scale (NIHSS), early neurological improvement at 24 hours, modified Rankin Scale (mRS) shift, percentage of mRS 0-1 and mRS 0-2 at 90 days.</p><p><strong>Results: </strong>We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase. Following PSM, 1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase. No significant differences were observed in rates of sICH (1.8% vs 1.98%, p=0.864) or other safety outcomes. Moreover, TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage (OR: 0.51, 95% CI: 0.31 to 0.86, p=0.012). A higher proportion of patients achieving early neurological improvement at 24 hours (OR: 1.76, 95% CI: 1.48 to 2.09, p=0.000), better 90-day mRS (OR: 0.67, 95% CI: 0.57 to 0.79, p=0.000) as well as higher percentages of 90-day mRS 0-1 (OR: 1.27, 95% CI: 1.05 to 1.54, p=0.012) and mRS 0-2 (OR: 1.41, 95% CI: 1.14 to 1.75, p=0.001) compared with alteplase.</p><p><strong>Conclusions: </strong>Thrombolysis with TNK is not associated with an increased risk of sICH, and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631194","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":"Correlation of enlarged perivascular spaces in basal ganglion and cancer-associated stroke: a case-control study in China.","authors":"Jielong Wu, Ganji Hong, Liangcheng Zheng, Jiedong Zhao, Lu Yu, Chuya Jing, Qiuhong Zhang, Chen Wang, Xiaodong Yuan, Qing Lin, Zhanxiang Wang, Qilin Ma, Jie Fang","doi":"10.1136/svn-2024-003287","DOIUrl":"https://doi.org/10.1136/svn-2024-003287","url":null,"abstract":"<p><strong>Introduction: </strong>The incidence of cancer-associated ischaemic stroke (IS) is increasingly prevalent. This study aimed to assess the levels of enlarged perivascular spaces in basal ganglion (BG-EPVS) in cancer-associated patients who had a stroke compared with the control group, and to investigate the diagnostic utility of BG-EPVS in the context of cancer-associated stroke.</p><p><strong>Method: </strong>A matched case-control study was conducted in Xiamen, China. A total of 184 IS patients (cancer vs control=1:1) were recruited. The severity of BG-EPVS was graded using high-resolution MRI. Patients' gender, age, clinical risk factors, other imaging changes and laboratory findings information at admission were collected. Logistic regression models were constructed and subgroup analysis by cancer treatment.</p><p><strong>Result: </strong>Overall, 65.22% of the 184 subjects were male, with a mean (SD) age of 68.83±10.52 years. BG-EPVS had a significant influence on cancer-associated stroke (OR=1.85 (95% CI 1.29, 2.71), p=0.001) after adjusting for gender, age, clinical risk factors, other imaging changes and laboratory findings. The area under the curve of the diagnosis model that combined BG-EPVS and other factors was 0.848 (95% CI 0.787, 0.896), significantly higher than the other three models. Subgroup analysis suggested a heightened association between BG-EPVS and cancer-associated stroke within the cancer treatment group.</p><p><strong>Conclusion: </strong>In conclusion, this is the first study to assess the diagnosis values of BG-EPVS on cancer-associated stroke and helps us understand the pathogenesis of cancer-associated stroke. Our findings demonstrate the effectiveness of BG-EPVS in diagnosing IS patients who may carry underlying cancer.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631190","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":"CSA declaration of next-generation reperfusion therapy for ischaemic stroke.","authors":"","doi":"10.1136/svn-2024-003110","DOIUrl":"10.1136/svn-2024-003110","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"459-460"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486523","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":"Thrombolysis for ischaemic stroke despite direct oral anticoagulation.","authors":"Jan C Purrucker, Thomas R Meinel, Duncan Wilson, Ying Xian, Teddy Y Wu, David J Seiffge","doi":"10.1136/svn-2023-002727","DOIUrl":"10.1136/svn-2023-002727","url":null,"abstract":"<p><p>Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"464-466"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724555","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}