Journal of Investigative Medicine最新文献

{"title":"Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion.","authors":"Zhixin Cao, David Wang, Xueyan Feng, Pengfei Yang, Hao Wang, Ziqi Xu, Yahui Hao, Wanxing Ye, Fengwei Chen, Liyuan Wang, Manjun Hao, Na Wu, Kai-Xuan Yang, Yunyun Xiong, Yongjun Wang","doi":"10.1136/svn-2023-002964","DOIUrl":"https://doi.org/10.1136/svn-2023-002964","url":null,"abstract":"<p><strong>Introduction: </strong>To compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT).</p><p><strong>Methods: </strong>Data on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman's rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes.</p><p><strong>Results: </strong>Among 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth.</p><p><strong>Conclusion: </strong>The automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319585","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":"Application of bedside HINTS, ABCD² score and truncal ataxia to differentiate cerebellar-brainstem stroke from vestibular neuritis in the emergency room.","authors":"Xinmin Liu, Zhaoxia Li, Yi Ju, Xingquan Zhao","doi":"10.1136/svn-2023-002779","DOIUrl":"https://doi.org/10.1136/svn-2023-002779","url":null,"abstract":"<p><strong>Background and purpose: </strong>Acute vestibular syndrome (AVS) typically manifests as isolated dizziness or vertigo with no apparent neurological impairments. However, distinguishing life-threatening stroke from innocuous peripheral vestibular lesions in the emergency room (ER) remains challenging. This study aimed to explore the ability of the head impulse-nystagmus-test of skew (HINTS) combined with truncal ataxia or ABCD² score to differentiate stroke from peripheral vestibular disease in patients with AVS in the ER.</p><p><strong>Methods: </strong>We prospectively recruited 121 patients with AVS from December 2022 to June 2023, 69 of whom presented with vestibular neuritis (VN) and the remaining with posterior circulation stroke (PCS). We analysed the HINTS results, truncal ataxia and ABCD² score and compared the sensitivity and specificity among HINTS, truncal ataxia, ABCD² score and their combinations using the McNemar test for paired samples.</p><p><strong>Results: </strong>HINTS combined with grade 2-3 truncal ataxia achieved significantly higher sensitivity than that of isolated HINTS in differentiating PCS from VN (100% vs 88.5%, p=0.031). The specificity of HINTS plus grade 2-3 truncal ataxia did not significantly differ from that of isolated HINTS (p=0.125); however, the combination of ABCD² score and HINTS did not improve the diagnostic accuracy. The sensitivity of ABCD² score ≥4 plus grade 2-3 truncal ataxia was significantly higher than those of isolated ABCD² score ≥4 or isolated grade 2-3 truncal ataxia (p=0.016 and p<0.001, respectively) and not significantly lower than that of isolated HINTS (p=0.508).</p><p><strong>Conclusion: </strong>Compared with the ABCD² score, the truncal ataxia is of more valuable assistance to HINTS in differentiating PCS. Although the combination of ABCD² score and truncal ataxia has a significant implication, it is not a replacement for HINTS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295032","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":"TIMP1 protects against blood-brain barrier disruption after subarachnoid haemorrhage by inhibiting ubiquitination of astrocytic β1-integrin.","authors":"Tianchi Tang, Huaijun Chen, Libin Hu, Jingya Ye, Chaohui Jing, Chaoran Xu, Xinyan Wu, Yike Chen, Zihang Chen, Hang Zhou, Linfeng Fan, Xiongjie Fu, Cong Qian, Jingsen Chen, Zhongju Tan, Jing Liu, Hanhai Zeng, Gao Chen, Fuyi Liu","doi":"10.1136/svn-2023-002956","DOIUrl":"https://doi.org/10.1136/svn-2023-002956","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes regulate blood-brain barrier (BBB) integrity, whereas subarachnoid haemorrhage (SAH) results in astrocyte dysregulation and BBB disruption. Here, we explored the involvement of tissue inhibitor of matrix metalloprotease-1 (TIMP1) in astrocyte-mediated BBB protection during SAH, along with its underlying mechanisms.</p><p><strong>Methods: </strong>C57BL/6J mice were used to establish a model of SAH. The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein (rm-TIMP1; 250 µg/kg). The roles of TIMP1 and its effector β1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid or β1-integrin RNAi. The molecular mechanisms underlying TIMP1 and β1-integrin interactions were explored in primary cultured astrocytes stimulated with red blood cells (RBCs).</p><p><strong>Results: </strong>TIMP1 was upregulated after SAH. Administration of rm-TIMP1 mitigated SAH-induced early brain injury (EBI) in male and female mice. TIMP1 was primarily expressed in astrocytes; its overexpression in astrocytes led to increased β1-integrin expression in astrocytes, along with the preservation of astrocytic endfoot attachment to the endothelium and subsequent recovery of endothelial tight junctions. All of these effects were reversed by the knockdown of β1-integrin in astrocytes. Molecular analysis showed that TIMP1 overexpression decreased the RBC-induced ubiquitination of β1-integrin; this effect was partially achieved by inhibiting the interaction between β1-integrin and the E3 ubiquitin ligase Trim21.</p><p><strong>Conclusion: </strong>TIMP1 inhibits the interaction between β1-integrin and Trim21 in astrocytes, thereby rescuing the ubiquitination of astrocytic β1-integrin. It subsequently restores interactions between astrocytic endfeet and the endothelium, as well as BBB integrity, eventually mitigating SAH-induced EBI.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132889","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":"Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial.","authors":"Chunjuan Wang, Hong-Qiu Gu, Qiang Dong, Anding Xu, Ning Wang, Yi Yang, Feng Wang, Yongjun Wang","doi":"10.1136/svn-2023-002938","DOIUrl":"https://doi.org/10.1136/svn-2023-002938","url":null,"abstract":"<p><strong>Background: </strong>Edaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol (TASTE) trial demonstrated its superior efficacy over edaravone alone for acute ischaemic stroke (AIS) patients. However, its efficacy in individuals undergoing endovascular therapy (EVT) remains uncertain.</p><p><strong>Aim: </strong>To clarify the rationale and design of the TASTE II (TASTE-2) trial.</p><p><strong>Design: </strong>The TASTE-2 is a multicentre, double-blind, randomised, placebo-controlled trial designed to evaluate the efficacy and safety of edaravone dexborneol in patients with AIS and large-vessel occlusion in the anterior circulation. The eligible participants, presenting with a National Institute of Health Stroke Scale score between 6 and 25 (range 0-42, with larger values suggesting severe neurological dysfunction) and an Alberta Stroke Program Early Computed Tomography Score ranging from 6 to 10 (range 0-10, with smaller values suggesting larger infarction) within the initial 24 hours after symptom onset, will be randomly allocated to either the edaravone dexborneol group or the placebo group in equal proportions prior to thrombectomy. The treatment will be continuously administered for a duration of 10-14 days. A follow-up period of 90 days will be implemented for all participants.</p><p><strong>Study outcomes: </strong>The primary efficacy outcome is defined as achieving favourable functional independence, measured by a modified Rankin Scale of 0-2 at 90 days. The primary safety outcome focuses on the incidence of serious adverse events.</p><p><strong>Discussion: </strong>The TASTE-2 trial will provide evidence to determine whether the administration of edaravone dexborneol in AIS patients undergoing EVT could yield significant improvements in neurological function.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111928","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":"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence, risk factors and prognostic value of atrial fibrillation detected after stroke after haemorrhagic versus ischaemic stroke.","authors":"Jiahuan Guo, Zixiao Li, Hongqiu Gu, Kaixuan Yang, Yanfang Liu, Jingjing Lu, Dandan Wang, Jiaokun Jia, Jia Zhang, Yongjun Wang, Xingquan Zhao","doi":"10.1136/svn-2023-002974","DOIUrl":"https://doi.org/10.1136/svn-2023-002974","url":null,"abstract":"<p><strong>Background and objectives: </strong>Prior evidence suggests that atrial fibrillation detected after stroke (AFDAS) is distinct from known atrial fibrillation (KAF), with particular clinical characteristics and impacts on outcomes in ischaemic stroke. However, the results remained inconsistent in ischaemic stroke, and the role of AFDAS in haemorrhagic stroke remains unclear. Therefore, we aimed to estimate the prevalence, risk factors and prognostic value of AFDAS in haemorrhagic stroke in comparison with ischaemic stroke.</p><p><strong>Methods: </strong>This was a multicentre cohort study. Patients who had an ischaemic and haemorrhagic stroke hospitalised in the Chinese Stroke Center Alliance hospitals were enrolled and classified as AFDAS, KAF or sinus rhythm (SR) based on heart rhythm. Univariate and multivariate logistic regression analyses were used to assess the prevalence, characteristics, risk factors and outcomes of AFDAS, KAF and SR in different stroke subtypes.</p><p><strong>Results: </strong>A total of 913 163 patients, including 818 799 with ischaemic stroke, 83 450 with intracerebral haemorrhage (ICH) and 10 914 with subarachnoid haemorrhage (SAH), were enrolled. AFDAS was the most common in ischaemic stroke. There were differences in the risk factor profile between stroke subtypes; older age is a common independent risk factor shared by ischaemic stroke (OR 1.06, 95% CI 1.06 to 1.06), ICH (OR 1.08, 95% CI 1.07 to 1.09) and SAH (OR 1.07, 95% CI 1.05 to 1.10). Similar to KAF, AFDAS was associated with an increased risk of in-hospital mortality compared with SR in both ischaemic stroke (OR 2.23, 95% CI 1.94 to 2.56) and ICH (OR 2.84, 95% CI 1.84 to 4.38).</p><p><strong>Discussion: </strong>There are differences in the prevalence, characteristics and risk factors for AFDAS and KAF in different stroke subtypes. AFDAS was associated with an increased risk of mortality compared with SR in both ischaemic stroke and ICH. Rhythm monitoring and risk factor modification after both ischaemic and haemorrhagic stroke are essential in clinical practice. More emphasis and appropriate treatment should be given to AFDAS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747589","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":"Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model.","authors":"Ximing Nie, Jinxu Yang, Xinxin Li, Tianming Zhan, Dongdong Liu, Hongyi Yan, Yufei Wei, Xiran Liu, Jiaping Chen, Guoyang Gong, Zhenzhou Wu, Zhonghua Yang, Miao Wen, Weibin Gu, Yuesong Pan, Yong Jiang, Xia Meng, Tao Liu, Jian Cheng, Zixiao Li, Zhongrong Miao, Liping Liu","doi":"10.1136/svn-2023-002500","DOIUrl":"https://doi.org/10.1136/svn-2023-002500","url":null,"abstract":"<p><strong>Background: </strong>Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation.</p><p><strong>Methods: </strong>Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction.</p><p><strong>Results: </strong>Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/).</p><p><strong>Conclusions: </strong>The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713208","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":"Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries.","authors":"Bernhard M Siepen, Elisabeth Forfang, Mattia Branca, Boudewijn Drop, Madlaine Mueller, Martina B Goeldlin, Mira Katan, Patrik Michel, Carlo Cereda, Friedrich Medlin, Nils Peters, Susanne Renaud, Julien Niederhauser, Emmanuel Carrera, Timo Kahles, Georg Kägi, Manuel Bolognese, Stephan Salmen, Marie-Luise Mono, Alexandros A Polymeris, Susanne Wegener, Werner Z'Graggen, Johannes Kaesmacher, Michael Schaerer, Biljana Rodic, Espen Saxhaug Kristoffersen, Kristin T Larsen, Torgeir Bruun Wyller, Bastian Volbers, Thomas R Meinel, Marcel Arnold, Stefan T Engelter, Leo H Bonati, Urs Fischer, Ole Morten Rønning, David J Seiffge","doi":"10.1136/svn-2023-002813","DOIUrl":"https://doi.org/10.1136/svn-2023-002813","url":null,"abstract":"<p><strong>Background: </strong>We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.</p><p><strong>Methods: </strong>This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months.</p><p><strong>Results: </strong>Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)).</p><p><strong>Conclusions: </strong>The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713207","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":"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous tenecteplase compared with alteplase for minor ischaemic stroke: a secondary analysis of the AcT randomised clinical trial.","authors":"Radhika Nair, Nishita Singh, Mahesh Kate, Negar Asdaghi, Robert Sarmiento, Fouzi Bala, Shelagh B Coutts, MacKenzie Horn, Alexandre Y Poppe, Heather Williams, Ayoola Ademola, Ibrahim Alhabli, Faysal Benali, Houman Khosravani, Gary Hunter, Aleksander Tkach, Herbert Alejandro Manosalva Alzate, Aleksandra Pikula, Thalia Field, Anurag Trivedi, Dar Dowlatshahi, Luciana Catanese, Ashfaq Shuaib, Andrew Demchuk, Tolulope Sajobi, Mohammed A Almekhlafi, Richard H Swartz, Bijoy Menon, Brian H Buck","doi":"10.1136/svn-2023-002828","DOIUrl":"https://doi.org/10.1136/svn-2023-002828","url":null,"abstract":"<p><strong>Background: </strong>In ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial.</p><p><strong>Methods: </strong>The AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0-1 at 90-120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH).</p><p><strong>Results: </strong>Of the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0-1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)).</p><p><strong>Conclusion: </strong>In this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724603","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}