Journal of Investigative Medicine最新文献

{"title":"Should patients with minor strokes be given thrombolytics?","authors":"Xun Wang, Yi Dong, Qiang Dong, David Wang","doi":"10.1136/svn-2024-003451","DOIUrl":"10.1136/svn-2024-003451","url":null,"abstract":"<p><p>Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29-43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2 (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890664","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":"Multicentre prospective, randomised open-label, endpoint-blinded study to evaluate the safety and efficacy of propranolol for the prevention of stroke-associated pneumonia in patients with intracerebral haemorrhage (PROCHASE): rationale and design.","authors":"Bin Gao, Kaibin Shi, Yuesong Pan, Shunnan Ge, Yanfang Liu, Jing Yan, Arthur Liesz, Andreas Meisel, Yan Qu, Xingquan Zhao, Fu-Dong Shi","doi":"10.1136/svn-2024-003630","DOIUrl":"https://doi.org/10.1136/svn-2024-003630","url":null,"abstract":"<p><strong>Background: </strong>Stroke-induced transient immune suppression is believed to contribute to post-stroke infections. The β-adrenergic receptor antagonist, propranolol, has been shown to prevent stroke-associated pneumonia (SAP) via reversing post-stroke immunosuppression in preclinical studies and in retrospective analysis in stroke patients. However, whether propranolol can reduce the risk of SAP has not been tested in prospective, randomised controlled trials.</p><p><strong>Aim: </strong>To describe the rationale and design of a multicentre, prospective, open-label, endpoint-blinded, randomised controlled study to evaluate the safety and efficacy of propranolol hydrochloride injection for the prevention of SAP in patients with intracerebral haemorrhage (ICH) (PROCHASE).</p><p><strong>Design: </strong>In this investigator-initiated trial, we compare the safety of the standard medical treatment to standard medical treatment plus intravenous propranolol hydrochloride administration (5 mg daily on days 1-7) in patients with ICH and the efficacy of this intervention to reduce the occurrence of SAP. All patients will be followed up for 90±7 days.</p><p><strong>Study outcomes: </strong>The primary efficacy outcome is SAP within 7±1 days diagnosed by the defined algorithm based on a diagnosis of SAP recommendations from the pneumonia in stroke consensus group. The primary safety outcome is defined as severe or moderate bradycardia within 7±1 days. The secondary outcome is a modified Rankin score of 0-3 at 90±7 days after randomisation.</p><p><strong>Discussion: </strong>The PROCHASE trial aims to generate clinical evidence regarding the safety and efficacy of propranolol in preventing SAP in patients with ICH.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911032","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":"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":" ","pages":"604-612"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791631/pdf/","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":"OA","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":"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":" ","pages":"730-737"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791642/pdf/","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":"OA","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":"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":" ","pages":"631-639"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791634/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk stratification of delayed causative aneurysm detection and long-term outcome in angiographically negative spontaneous subarachnoid haemorrhage.","authors":"Jie Wang, Jian-Feng Meng, Shuo Wang, Ji-Zong Zhao, Yong Cao","doi":"10.1136/svn-2023-002546","DOIUrl":"10.1136/svn-2023-002546","url":null,"abstract":"<p><strong>Background: </strong>The risk factors of aetiology and poor outcome in angiographically negative subarachnoid haemorrhage (anSAH) were unclearly.</p><p><strong>Methods: </strong>The authors performed a retrospective review of a prospectively maintained database for anSAH patients between 2014 and 2018. AnSAH was defined as SAH presents in CT with no underlying vascular abnormality on initial digital subtraction angiography (DSA) within 72 hours of admission. Baseline and follow-up information, including medical history, bleeding pattern (perimesencephalic angiogram-negative SAH (PAN-SAH) and non-PAN-negative SAH (NPAN-SAH)), modified Fisher Scale (mFS), Glasgow Coma Score (GCS), Hunt-Hess grade, repeated imaging and causative vascular lesions and follow-up modified Rankin Scale (mRS) were reviewed. Poor outcome was defined as mRS scored 3-6 at last clinical follow-up.</p><p><strong>Results: </strong>Among 303 enrolled patients, 272 patients underwent at least once repeated imaging examination (median follow-up time, 3.0 months). Twenty-one (7.7%) aneurysms were detected. Multivariate logistic analysis showed that NPAN-SAH and mFS 3-4 were associated with a high rate of aneurysm detection in anSAH patients. Based on risk stratification, the aneurysm detection rate in the high-risk group (both NPAN-SAH and mFS 3-4) was as high as 20.370 per 100 person-years. Furthermore, of 251 non-aneurysm anSAH patients, after a total follow-up time of 1265.83 patient-years, poor outcome occurred in 18 (7.2%) patients. Multivariate Cox analysis found that NPAN-SAH and GCS 3-12 were associated with a high rate of poor outcome of anSAH. The cumulative 5-year incidence rate for poor outcome in the non-aneurysm anSAH patients in the high-risk group (both NPAN-SAH and GCS 3-12) was as high as 75.302 per 100 person-years.</p><p><strong>Conclusions: </strong>Even in anSAH confirmed by initial DSA, patients with NPAN-SAH and mFS 3-4 should be monitored for delayed causative aneurysm detection, meanwhile in non-aneurysm anSAH patients, NPAN-SAH and initial functional impairment are associated with poor prognosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"595-603"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724554","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":"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":"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":" ","pages":"671-684"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791639/pdf/","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":"OA","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":"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":" ","pages":"685-692"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791636/pdf/","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":"OA","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":"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":" ","pages":"640-651"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791643/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial.","authors":"Shuya Li, Runqi Wangqin, Yuesong Pan, Aoming Jin, Hao Li, Lee H Schwamm, Marc Fisher, Bruce C V Campbell, Mark W Parsons, Ziran Wang, Hongguo Dai, Deyang Li, Runhui Li, Junhai Wang, David Wang, Yilong Wang, Xingquan Zhao, Zixiao Li, Huaguang Zheng, Yunyun Xiong, Xia Meng, Yongjun Wang","doi":"10.1136/svn-2023-002694","DOIUrl":"10.1136/svn-2023-002694","url":null,"abstract":"<p><strong>Background: </strong>The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.</p><p><strong>Methods: </strong>This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.</p><p><strong>Results: </strong>Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min.</p><p><strong>Conclusions: </strong>In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"613-622"},"PeriodicalIF":2.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724604","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}