Journal of Investigative Medicine最新文献

{"title":"Influence of impaired renal function on the outcomes of patients with acute ischaemic stroke treated with intravenous tenecteplase and alteplase: a post hoc analysis of the TRACE-2 trial.","authors":"Yu Wu, Yuesong Pan, Mengxing Wang, Xia Meng, Yilong Wang, Shuya Li, Yongjun Wang, Yilun Zhou, Wanliang Du","doi":"10.1136/svn-2024-003726","DOIUrl":"https://doi.org/10.1136/svn-2024-003726","url":null,"abstract":"<p><strong>Objective: </strong>Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications, particularly for the drug tenecteplase. Therefore, we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment (IVT) in patients with acute ischaemic stroke (AIS).</p><p><strong>Methods: </strong>A post hoc analysis of a randomised controlled trial (ClinicalTrials gov. NCT04797013) was conducted. Participants who received IVT with tenecteplase and alteplase (0.25 and 0.9 mg/kg, respectively) within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows: (1) ≥90 mL/min/1.73 m²,normal renal function; (2) 60-89 mL/min/1.73 m², mildly decreased renal function; and (3) <60 mL/min/1.73 m², moderately to severely decreased renal function. Patients stratified based on the normal renal function were used as the references. The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage (sICH) occurrence within 36 hours, respectively.</p><p><strong>Results: </strong>In intravenous tenecteplase-treated patients, mildly decreased renal function (OR 3.10; 95% CI: 1.41 to 6.78) and moderately to severely decreased renal function (OR: 8.03; 95% CI: 2.76 to 23.38) showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function. Among patients administered intravenous alteplase, those with a moderate-to-severe decrease in renal function exhibited an elevated risk of sICH (adjusted OR: 10.01; 95% CI: 1.61 to 62.15) and all-cause mortality (adjusted OR: 4.54; 95% CI: 1.48 to 13.91). Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.</p><p><strong>Conclusions: </strong>A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659481","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":"MetS in the prediction of asymptomatic intracranial arterial stenosis: the potential mediating role of hsCRP.","authors":"Jie Liu, Yang Liu, Longyou Zhang, Wenbo Li, Ying Zhang, Yin Hong, Juan Li, Yun Yun Duan, Huaguang Zheng","doi":"10.1136/svn-2024-003779","DOIUrl":"https://doi.org/10.1136/svn-2024-003779","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the relationships between metabolic syndrome (MetS) and its severity score (Metsss) with asymptomatic intracranial arterial stenosis (aICAS) while also assessing the additional effect of high-sensitivity C reactive protein (hsCRP).</p><p><strong>Methods: </strong>This cross-sectional study included 2390 individuals who underwent health examinations at our centre from June 2019 to August 2023. Participants received physical examinations, laboratory tests and magnetic resonance angiography evaluations. MetS was defined by the modified acknowledged criteria and quantified by Metsss. Logistic regression, interaction analysis and mediation analysis were employed.</p><p><strong>Results: </strong>Among the 2390 participants, 135 (5.65%) had aICAS, and 726 (30.40%) had MetS. After adjusting for confounders, MetS was significantly associated with aICAS (OR: 1.68, 95% CI: 1.16 to 2.43, p=0.006). The prevalence of aICAS increased significantly from 3.6% to 8.6% as the number of MetS components increased. Higher quartiles of Metsss also significantly increased aICAS risk (P for trend <0.001). After multivariable adjustment, MetS (p=0.001) and elevated Metsss (p<0.001) were only associated with posterior circulation aICAS (vs anterior). Furthermore, participants with both MetS and elevated hsCRP levels had a greater risk for aICAS (OR: 2.32, 95% CI: 1.36 to 3.96, p=0.002). hsCRP mediated the association between MetS and alCAS in participants ≤65 years old.</p><p><strong>Conclusions: </strong>MetS and Metsss were independently associated with the risk of aICAS. The mediating effect of hsCRP on the relationship between MetS and aICAS appears to be age-dependent. These findings offer valuable insights into clinical decision making of aICAS and further improve the primary stroke prevention.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651579","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":"LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.","authors":"Yanfei Tian, Yan Wang, Yupeng Zhao, Chang Liu, Xiaoyu Zhang, Yan Zhang, Zhenghui Wu, Yue Kong, Bo Wang, Huaxing Zhang, Xiaona Du, Hailin Zhang, Huiran Zhang","doi":"10.1136/svn-2024-003675","DOIUrl":"https://doi.org/10.1136/svn-2024-003675","url":null,"abstract":"<p><strong>Background: </strong>The increased permeability of the blood-brain barrier (BBB) is a critical contributor to the high mortality following ischaemic stroke. However, the mechanisms regulating BBB integrity remain poorly understood. Leucine-rich repeat-containing 8A (LRRC8A) is a chloride channel critical for cellular volume homeostasis and plays a key role in regulating neuronal injury during ischaemia. However, its impact on BBB function is currently unclear.</p><p><strong>Methods: </strong>A transient middle cerebral artery occlusion model was established to investigate the impact of LRRC8A on BBB integrity. Laser speckle contrast imaging was used to monitor cortical blood flow. Primary mouse and human brain microvascular endothelial cells (m/hBMVECs) were subjected to oxygen-glucose deprivation (OGD) and re-oxygenation for varying durations. Patch-clamp recordings were performed to measure volume-regulated chloride currents. Immunostaining was conducted to evaluate protein expression. Cell permeability was evaluated with transwell assay.</p><p><strong>Results: </strong>LRRC8A deletion in endothelial cells ameliorates the infarct area and mitigates BBB leakage. Ischaemia dramatically upregulates the expression of LRRC8A in endothelial cells, concurrently downregulating tight junction proteins. OGD exposure augments the VRCC current mediated by LRRC8A in BMVECs. In contrast, inhibiting LRRC8A promotes the expression of ZO-1 and VE-cadherin, thereby preserving the integrity of endothelial cells. With-no-lysine kinase 1 (WNK1) inhibition contributes to LRRC8A-induced BBB damage post-ischaemic stroke. Eupatorin, a newly identified LRRC8A inhibitor, exerts neuroprotective effects against ischaemic stroke.</p><p><strong>Conclusions: </strong>LRRC8A in BMVECs plays a pivotal role in modulating BBB integrity, a process regulated by WNK1. As an LRRC8A inhibitor, Eupatorin holds the potential for ischaemic stroke therapy.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651578","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":"Analysis of prehospital delay in acute ischaemic stroke and its influencing factors: a multicentre prospective case registry study in China.","authors":"Ying Su, Wenwei Qi, Yanni Yu, Jiaqian Zhu, Xin Shi, Xiaohong Wu, Feng Chi, Runyu Xia, Limin Qin, Liming Cao, Yan Yang, Qin Liu, Xiaoxiang Peng, Guobing Huang, Jinyan Chen, Yidong Xue, Wenbiao Guan, Dan Gao, Bin Ye, Lijie Ren","doi":"10.1136/svn-2024-003535","DOIUrl":"10.1136/svn-2024-003535","url":null,"abstract":"<p><strong>Background: </strong>Prehospital delay in acute ischaemic stroke (AIS) remains prevalent in China. We aimed to assess the status of the onset-to-door time (ODT) in AIS and analyse its influencing factors.</p><p><strong>Methods: </strong>Data were collected from a prospective multicentre hospital-based registry (China National Cerebrovascular Disease Prevention and Control Project Management Special Database) of patients with AIS involving 21 hospitals across different economic and geographical regions in China in 2022. The Mann-Whitney U test or t-test was used for between-group comparisons. Factors influencing ODT ≤3 hours were analysed using a binary logistic regression model.</p><p><strong>Results: </strong>Of the included 12 484 patients (attended middle school or below, 69.2%), females had a higher illiteracy rate (13.1%) than males (4.8%); 94.8% were living with others at illness onset; 22.5% of patients/family members were aware of the stroke emergency map (SEM, but only 7.3% were transported by SEM; 76.8% lived within 20 km of the first visited hospital. Significant differences occurred in modes of arrival at hospitals among cities of different sizes (χ²=74.882, p<0.001). Being in a medium-sized (OR 0.65, 95% CI 0.50 to 0.86); large (OR 0.61, 95% CI 0.47 to 0.79) or extralarge city (OR 0.60, 95% CI 0.46 to 0.78); experiencing cardiogenic embolism (OR 0.65, 95% CI 0.50 to 0.86) or stroke of undetermined aetiology (OR 0.69, 95% CI 0.52 to 0.92); stroke onset between 18:00 and 23:59 (OR 0.71, 95% CI 0.60 to 0.85); distance <20 km from onset location to the hospital (OR 0.47, 95% CI 0.41 to 0.54); being transported by SEM (OR 0.31, 95% CI 0.26 to 0.36) and having initial National Institutes of Health Stroke Scale scores of 5-15 (OR 0.63, 95% CI 0.57 to 0.71) or 16-42 (OR 0.32, 95% CI 0.27 to 0.39) were independent factors favouring ODT ≤3 hours. Conversely, being transferred between hospitals during transportation (OR 3.31, 95% CI 2.66 to 4.14); experiencing wake-up stroke (OR 2.00, 95% CI 1.67 to 2.38); symptom-onset including dizziness (OR 1.28, 95% CI 1.10 to 1.47) and prestroke modified Rankin scale (mRS) score of 2-3 (OR 1.58, 95% CI 1.30 to 1.92) or 4-5 (OR 1.48, 95% CI 1.02 to 2.15) tended to indicate ODT >3 hours.</p><p><strong>Conclusions: </strong>Urban scale, stroke type, onset time, distance from initial location to the first hospital visit, transportation method, stroke symptoms, prestroke mRS score and stroke severity significantly influenced prehospital delay. Our findings can facilitate the development of targeted policies.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558315","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":"Oxidised low-density lipoprotein and adverse outcome in patients with acute mild ischaemic stroke or high-risk TIA: a secondary analysis of the INSPIRES randomised clinical trial.","authors":"Yaowei Ding, Lingling Jiang, Tingting Wang, Yuxin Chen, Yuesong Pan, Xiaotong Li, Hongyi Yan, Weiqi Chen, Guojun Zhang, Yilong Wang","doi":"10.1136/svn-2024-003664","DOIUrl":"https://doi.org/10.1136/svn-2024-003664","url":null,"abstract":"<p><strong>Background: </strong>Research data regarding the correlation between elevated oxidised low-density lipoprotein (oxLDL) cholesterol concentrations and unfavourable clinical outcomes in individuals experiencing minor acute ischaemic cerebrovascular events or transient ischaemic attack (TIA) with presumed atherosclerotic aetiology are still limited.</p><p><strong>Methods: </strong>This investigation incorporated a cohort of 5814 participants derived from the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis clinical trial. The core laboratory conducted blinded measurements of baseline plasma oxLDL concentrations. Multivariable Cox regression analyses were employed to assess the correlations between oxLDL levels and adverse clinical events. The principal endpoint for efficacy assessment was defined as the occurrence of stroke within a 90-day follow-up period. Additional secondary endpoints encompassed composite vascular events during the same observation window. The main safety endpoint assessed was the occurrence of bleeding events of moderate to severe intensity.</p><p><strong>Results: </strong>The final analytical cohort comprised 5814 patients included in the final analysis. The mean age was 63.7±9.6 years, and 36.0% were female. The average concentration of circulating oxLDL was 36.62 µg/dL. Elevated oxLDL concentrations demonstrated a potential correlation with heightened stroke risk (T3 vs T1: HR 1.39, 95% CI 1.04 to 1.85), ischaemic stroke (T3 vs T1: HR 1.31, 95% CI 0.98 to 1.76) and composite vascular events (T3 vs T1: HR 1.36, 95% CI 1.02 to 1.81) within 90 days. An increased concentration of oxLDL demonstrated a significant association with elevated susceptibility to moderate and severe haemorrhagic events (T3 vs T1: HR 3.61, 95% CI 1.26 to 10.34) within 90 days.</p><p><strong>Conclusion: </strong>Increased concentrations of oxLDL demonstrated an independent correlation with both stroke recurrence and the occurrence of moderate-to-severe haemorrhagic events in individuals presenting with acute minor ischaemic stroke or TIA at elevated risk, accompanied by intracranial or extracranial atherosclerotic lesions.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517119","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":"Role of histone deacetylases and sirtuins in the ischaemic stroke: a protocol for a systematic review and meta-analysis of animal studies.","authors":"Ali Majdi, Hossein Mostafavi, Ali Moharrami, Shahin Yaraghi, Amirreza Ghaffari Tabrizi, Morteza Dojahani, Erfan Alirezapour, Kamyar Mansori","doi":"10.1136/svn-2024-003235","DOIUrl":"10.1136/svn-2024-003235","url":null,"abstract":"<p><strong>Background: </strong>Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.</p><p><strong>Methods: </strong>This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes.</p><p><strong>Discussion: </strong>No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.</p><p><strong>Systematic review registration: </strong>This systematic review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"129-135"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088422","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":"Patient-reported outcome measure and its application in patients with stroke: item response theory.","authors":"Jia Ma, Jinma Ren, Joseph C Cappelleri","doi":"10.1136/svn-2024-003166","DOIUrl":"10.1136/svn-2024-003166","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"1-4"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184677","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":"Clinical implications of haemodynamics in symptomatic intracranial atherosclerotic stenosis by computational fluid dynamics modelling: a systematic review.","authors":"Yu Liu, Shuang Li, Haipeng Liu, Xuan Tian, Yuying Liu, Ziqi Li, Thomas W Leung, Xinyi Leng","doi":"10.1136/svn-2024-003202","DOIUrl":"10.1136/svn-2024-003202","url":null,"abstract":"<p><strong>Background: </strong>Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.</p><p><strong>Methods: </strong>Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.</p><p><strong>Results: </strong>19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.</p><p><strong>Conclusions: </strong>CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"16-24"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162693","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":"Exploring the relationship between embolic acute stroke distribution and supra-aortic vessel patency: key findings from an in vitro model study.","authors":"Aglae Velasco Gonzalez, Cristina Sauerland, Dennis Görlich, Joaquin Ortega-Quintanilla, Astrid Jeibmann, Andreas Faldum, Werner Paulus, Walter Heindel, Boris Buerke","doi":"10.1136/svn-2023-003024","DOIUrl":"10.1136/svn-2023-003024","url":null,"abstract":"<p><strong>Background: </strong>We investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency.</p><p><strong>Methods: </strong>For this experimental analysis, we created a silicone model of the extracranial and intracranial circulations using a blood-mimicking fluid under physiological pulsatile flow. We examined the sequence of embolus lodgment on injecting 104 frangible clot analogues (406 emboli) through the right internal carotid artery (CA) as SAV patency changed: (a) all SAV patent (baseline), (b) emboli from a CA occlusion, (c) emboli contralateral to a CA occlusion and (d) occlusion of the posterior circulation. The statistical analysis included a descriptive analysis of thrombi location after occlusion (absolute and relative frequencies). Sequences of occlusions were displayed in Sankey flow charts for the four SAV conditions. Associations between SAV conditions and occlusion location were tested by Fisher's exact test. Two-sided p values were compared with a significance level of 0.05.</p><p><strong>Results: </strong>The total number of emboli was 406 (median fragments/clot: 4 (IQR: 3-5)). Embolus lodgment was dependent on SAV patency (p<0.0001). In all scenarios, embolism lodging in the anterior cerebral artery (ACA) occurred after a previous middle cerebral artery (MCA) embolism (MCA first lodge: 96%, 100/104). The rate of ipsilateral ACA embolism was 28.9% (28/97) at baseline, decreasing significantly when emboli originated from an occluded CA (16%, 14/88). There were more bihemispheric embolisations in cases of contralateral CA occlusion (37%, 45/122), with bilateral ACA embolisms preceding contralateral MCA embolism in 56% of cases (14/25 opposite MCA and ACA embolism).</p><p><strong>Conclusions: </strong>All emboli in the ACA occurred after a previous ipsilateral MCA embolism. Bihemispheric embolisms were rare, except when there was a coexisting occlusion in either CA, particularly in cases of a contralateral CA occlusion.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"78-85"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088396","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":"Left atrial appendage closure in patients with atrial fibrillation and acute ischaemic stroke despite anticoagulation.","authors":"Avia Abramovitz Fouks, Shadi Yaghi, Magdy H Selim, Elif Gökçal, Alvin S Das, Ofer Rotschild, Scott B Silverman, Aneesh B Singhal, Sunil Kapur, Steven M Greenberg, Mahmut Edip Gurol","doi":"10.1136/svn-2024-003143","DOIUrl":"10.1136/svn-2024-003143","url":null,"abstract":"<p><strong>Background: </strong>The occurrence of acute ischaemic stroke (AIS) while using oral anticoagulants (OAC) is an increasingly recognised problem among nonvalvular atrial fibrillation (NVAF) patients. We aimed to elucidate the potential role of left atrial appendage closure (LAAC) for stroke prevention in patients with AIS despite OAC use (AIS-despite-OAC).</p><p><strong>Methods: </strong>We retrospectively collected baseline and follow-up data from consecutive NVAF patients who had AIS-despite-OAC and subsequently underwent endovascular LAAC, between January 2015 and October 2021. The primary outcome measure was the occurrence of AIS after LAAC, and the safety outcome was symptomatic intracerebral haemorrhage (ICH).</p><p><strong>Results: </strong>29 patients had LAAC specifically because of AIS-despite-OAC. The mean age at the time of the procedure was 73.4±8.7, 13 were female (44.82%). The mean CHA₂DS₂-VASc score was 5.96±1.32, with an expected AIS risk of 8.44 per 100 patient-years. 14 patients (48%) had two or more past AIS-despite-OAC. After LAAC, 27 patients (93.10%) were discharged on OAC which was discontinued in 17 (58.62%) after transoesophageal echocardiogram at 6 weeks. Over a mean of 1.75±1.0 years follow-up after LAAC, one patient had an AIS (incidence rate (IR) 1.97 per 100 patient-years). One patient with severe cerebral microangiopathy had a small ICH while on direct OAC and antiplatelet 647 days after LAAC.</p><p><strong>Conclusions: </strong>LAAC in AIS-despite-OAC patients demonstrated a low annual AIS recurrence rate in our cohort (1.97%) compared with the expected IR based on their CHA₂DS₂-VASc scores (8.44%) and to recent large series of AIS-despite-OAC patients treated with OAC/aspirin only (5.3%-8.9%). These hypothesis-generating findings support randomised trials of LAAC in AIS-despite-OAC patients.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"120-128"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307224","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}