Journal of Investigative Medicine最新文献

{"title":"Response to 'comments on the article 'sex differences in the epidemiology of spontaneous and traumatic cervical artery dissections''.","authors":"Elke Schipani, Zafer Keser","doi":"10.1136/svn-2025-004158","DOIUrl":"https://doi.org/10.1136/svn-2025-004158","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732435","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":"Cerebrovascular cinematic rendering of multisystemic smooth muscle dysfunction syndrome.","authors":"Linggen Dong, Guanglei Li, Ming Lv","doi":"10.1136/svn-2024-003872","DOIUrl":"10.1136/svn-2024-003872","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587716","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 Study Design to Assess the Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke (EMPHASIS).","authors":"Yao Lu, Ling Guan, Meiyang Zhang, Qianqian Yang, Baoshan Qiu, Dongyang Zhou, Yicong Wang, Yuesong Pan, Luyan Wang, Xuejiao Zhou, Hui Qu, Xiaoling Liao, Liping Liu, Xingquan Zhao, Philip M Bath, S Claiborne Johnston, Pierre Amarenco, Yongjun Wang, Yilong Wang","doi":"10.1136/svn-2024-003577","DOIUrl":"https://doi.org/10.1136/svn-2024-003577","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and blood-brain barrier disruption may contribute to the pathogenesis of ischaemic stroke. Minocycline was shown to exert anti-inflammatory effects by attenuating microglial activation and protecting blood-brain barrier in preclinical studies. Previous small-scale clinical studies have suggested that minocycline may have a potential beneficial effect on prognosis in acute ischaemic stroke. However, the efficacy and safety of minocycline in patients with acute ischaemic stroke need to be further confirmed.</p><p><strong>Study aims: </strong>We designed the study, Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke (EMPHASIS), to evaluate the effect of minocycline in improving the functional outcome and the drug safety in patients with acute ischaemic stroke.</p><p><strong>Methods: </strong>The EMPHASIS study is a multicentre, randomised, double-blind, placebo-controlled trial aiming to recruit patients with acute ischaemic stroke. Patients who had ischaemic stroke within 72 hours of onset, a National Institutes of Health Stroke Scale score between 4 and 25 and Ia≤1 (moderate-to-severe) will be randomly allocated to either minocycline or placebo groups in a 1:1 ratio. Patients will receive minocycline (or placebo) with a loading dose of 200 mg, and subsequent 100 mg every 12 hours for 4 days. All patients will receive routine guideline-based treatment. The primary efficacy outcome is an excellent functional outcome assessed by the proportion of modified Rankin Scale score of 0-1 at 90±7 days. The main safety outcomes include the number of symptomatic intracranial haemorrhage at 24±2 hours and 6±1 days.</p><p><strong>Discussion: </strong>The EMPHASIS trial is the first phase III trial to investigate whether minocycline is effective and safe in improving functional outcome at 90 days in patients with moderate-to-severe acute ischaemic stroke. The data generated may provide valuable evidence of a potential anti-inflammation treatment for ischaemic stroke.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732407","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":"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":"Quantitative histopathological analysis of thrombi retrieved by mechanical thrombectomy and their association with stroke aetiology.","authors":"Zhiyi Jiang, Juan Huang, Shuntong Hu, Ruping Xiang, Longfeng Ran, Yiwei Chen, Dujie Xie, Panyao Long, Xiaobo Li, Yi Yuan","doi":"10.1136/svn-2024-003543","DOIUrl":"https://doi.org/10.1136/svn-2024-003543","url":null,"abstract":"<p><strong>Background and purpose: </strong>Approximately 25% of acute large vessel occlusive (LVO) ischaemic strokes are of unknown thrombotic origin, and there is a need to establish the aetiology to guide subsequent preventative measures. The aim of this study was to quantify thrombus composition in patients with LVO and explore associations between thrombus composition and stroke aetiology.</p><p><strong>Methods: </strong>Thrombi were extracted from 132 patients with acute ischaemic stroke. Erythrocytes, leucocytes and F+P (fibrin+platelet) proportions were assessed in tissue sections stained with H&E, while CD3⁺ T cells and neutrophil extracellular traps (NETs) were quantified in immunohistochemistry-stained sections. Thrombus components, clinical parameters and interventional variables were compared between different stroke subtypes defined by Trial of ORG 10172 in Acute Stroke Treatment criteria.</p><p><strong>Results: </strong>F+P composition was significantly higher (p<0.001) and erythrocyte proportions were significantly lower (p<0.001) in cardioembolic thrombi than in large artery atherosclerosis thrombi. The composition of thrombi from undetermined aetiology strokes resembled that from cardioembolic strokes. CD3⁺ T cell and NET proportions were not significantly different between stroke subtypes. CD3⁺ density per unit area was associated with the occlusive site, being significantly higher in the anterior circulation than the posterior circulation (p=0.004). Cardioembolic strokes were more common in the anterior circulation than large artery atherosclerosis strokes (p=0.002). Recanalisation time was significantly longer for large artery atherosclerosis emboli than for cardioembolic emboli (p=0.032).</p><p><strong>Conclusion: </strong>There is significant heterogeneity in thrombus composition among different stroke subtypes. The quantitative assessment of thrombus composition may be a useful biomarker of stroke aetiology, and strokes of undetermined aetiology may be more likely to have a cardioembolic origin.</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":"143659526","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":"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":"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":"Dual regulation of Atf3 and Lonp1 as therapeutic targets in cerebral ischaemia-reperfusion injury.","authors":"Weijian Fan, Min Zhou, Lin Zhou, Jindong Tong, Jinyun Tan, Weihao Shi, Bo Yu","doi":"10.1136/svn-2024-003324","DOIUrl":"https://doi.org/10.1136/svn-2024-003324","url":null,"abstract":"<p><strong>Background: </strong>Cerebral ischemia-reperfusion injury (CIRI) leads to cognitive dysfunction, neuronal death, and inflammation. Understanding the molecular mechanisms underlying CIRI is crucial for developing effective therapeutic strategies.</p><p><strong>Objective: </strong>This study aims to investigate the roles of activating transcription factor 3 (Atf3) and lon protease homolog 1 (Lonp1) in CIRI, particularly focusing on how Atf3 regulates Lonp1 expression and its effects on mitochondrial function.</p><p><strong>Methods: </strong>Single-cell transcriptomics and proteomic analyses were employed to explore Atf3's influence on Lonp1 and its subsequent impact on neuronal survival and apoptosis.</p><p><strong>Results: </strong>The findings indicate that Atf3 plays a crucial role in modulating Lonp1 expression, which in turn affects mitochondrial function, neuronal survival, and apoptotic pathways.</p><p><strong>Conclusion: </strong>This study provides new insights into the regulatory mechanisms of Atf3 and Lonp1 in CIRI, identifying potential therapeutic targets for managing ischemic brain injury and neurodegenerative diseases.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568649","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}