Journal of Investigative Medicine最新文献

{"title":"E<b>F</b>fects of Y-6 S<b>U</b>blingual Tablets for Pa<b>T</b>ients with Ac<b>U</b>te Ischemic St<b>R</b>ok<b>E</b> (FUTURE): a phase II, randomised, double-blind, double-dummy, placebo-controlled, parallel trial.","authors":"Yicong Wang, Baoshan Qiu, Ling Guan, Hui Qu, Yuesong Pan, Xiaochuan Huo, Liping Liu, Zhongrong Miao, Shuya Li, Zixiao Li, Xingquan Zhao, Yongjun Wang, Lei Wang, Xiaoling Liao, Yilong Wang","doi":"10.1136/svn-2024-003666","DOIUrl":"https://doi.org/10.1136/svn-2024-003666","url":null,"abstract":"<p><strong>Background: </strong>Acute ischaemic stroke, due to its high mortality and disability rates, imposes a significant economic and social burden worldwide. Typically, endovascular treatment within the therapeutic window is provided to salvage the ischaemic penumbra; however, even when recanalisation is successful during endovascular treatment, the clinical outcomes may still be disappointing. This highlights the necessity of further research, so as to discover better solutions to futile recanalisation and improve patient outcomes.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of Y-6 sublingual tablets (cilostazol and dexborneol) compared with a placebo in the treatment of patients with acute ischaemic stroke caused by large vessel occlusion.</p><p><strong>Method: </strong>The efficacy and safety of Y-6 sublingual tablets in patients with acute ischaemic stroke are evaluated in a phase II, randomised, double-blind, double-dummy, placebo-controlled, parallel clinical trial. Eligible patients having provided informed consent are randomised into five groups for a 28-day treatment period. The primary outcome is the percentage of patients achieving the modified Rankin Scale score of 0-1 at 90 days.</p><p><strong>Discussion: </strong>The EFfects of Y-6 SUblingual Tablets for PaTients with AcUte Ischemic StRokE trial assesses whether Y-6 sublingual tablets are effective and safe in improving the clinical outcomes of patients with acute ischaemic stroke caused by large vessel occlusion.</p><p><strong>Trial registration number: </strong>NCT06138834.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020304","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":"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":"2025-04-17","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":"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":"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":"2025-04-15","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":"Young stroke in Bangladesh: addressing rare cases with diagnostic challenges and much-needed solutions.","authors":"Manisha Das, Md Jubayer Hossain","doi":"10.1136/svn-2025-004178","DOIUrl":"https://doi.org/10.1136/svn-2025-004178","url":null,"abstract":"<p><p>Stroke is a leading cause of mortality and morbidity in Bangladesh, and young adults are increasingly affected. Common risk factors include hypertension, diabetes, dyslipidaemia, obesity and smoking, whereas rare causes include haematologic disorders, premature atherosclerosis, vasculopathy and arteritis. Treatment barriers include inadequate infrastructure, a lack of trained staff and high intervention costs. Bangladesh faces a scarcity of neurologists and well-equipped hospitals, necessitating strategies to mitigate the burden of stroke among young people. This editorial summarises the current knowledge regarding the aetiology, pathophysiology and challenges in diagnosing and treating stroke in young people in Bangladesh, while addressing rare vasculopathy. Initiatives to support young stroke survivors and their families were also discussed. Prospective cohort studies, such as the Norwegian Stroke in the Young Study, provide insights into optimising prevention and early intervention by assessing family history and subclinical vascular diseases, which have also been highlighted. Recommendations include advanced neuroimaging for risk assessment, incorporating patient care and rehabilitation into medical education, conducting relevant research and promoting healthy lifestyles through campaigns and training of the healthcare staff.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803330","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":"Learning curve and embolisation strategy in single-stage surgery combined embolisation and microsurgery for brain arteriovenous malformations: results from a nationwide multicentre prospective registry study.","authors":"Tengfei Yu, Heze Han, Li Ma, Yang Zhao, Yukun Zhang, Youxiang Li, Shuo Wang, Yu Chen, Xiaolin Chen","doi":"10.1136/svn-2025-004051","DOIUrl":"https://doi.org/10.1136/svn-2025-004051","url":null,"abstract":"<p><strong>Objective: </strong>Single-stage surgery combining embolisation and microsurgery has been increasingly used as a stand-alone procedure to cure complex AVMs. This study aimed to investigate the learning curve and embolisation strategy for single-stage surgery for AVMs.</p><p><strong>Methods: </strong>This prospective cohort study used data from the nationwide Multimodality Treatment for Brain Arteriovenous Malformations (MATCH) registry in China, conducted between August 2011 and December 2023. A total of 213 complex AVMs were divided into two groups. Group 1 included the first 25 patients. The 188 cases in group 2 included patients numbered 26-213. A case-crossover design was employed to evaluate the influence of complications, unfavourable outcomes and worsening modified Rankin Scale (mRS) score. Cumulative summation analysis was performed to assess the learning curve.</p><p><strong>Results: </strong>The rate of major complications decreased from 52.00% in group 1 to 34.57% in group 2 (p=0.089), while the rate of unfavourable outcomes decreased from 44.00% in group 1 to 18.62% in group 2 (p=0.004). The distribution of the three preoperative embolisation strategies was as follows: curative: 72.00% and 19.15%, palliative: 24.00% and 67.55%, and targeted: 4.00% and 13.30%, respectively (p<0.001). Multivariable regression analysis showed that surgeon experience was associated with a lower rate of unfavourable outcomes (p=0.022, OR=0.333). The mean follow-up duration was 49.90±20.54 months. The follow-up mRS score of 5-6 decreased from 9.09% in group 1 to 0.8% in group 2 (p=0.035).</p><p><strong>Conclusions: </strong>Performing single-stage combined surgery in 25 AVM cases is necessary to achieve reproducibility. Rates of major complications and unfavourable outcomes decreased significantly after the first 50 procedures. Palliative and targeted embolisation strategies are associated with a lower rate of unfavourable outcomes.</p><p><strong>Trial registration number: </strong>NCT04572568.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804598","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":"Stepwise improvement in intracerebral haematoma expansion prediction with advanced imaging: a comprehensive comparison of existing scores.","authors":"Umberto Pensato, Koji Tanaka, Chitapa Kaveeta, Johanna Ospel, MacKenzie Horn, David Rodriguez-Luna, Nishita Singh, Ankur Banerjee, Sanchea Wasyliw, Kennedy Horn, Amy Bobyn, Anneliese Neweduk, Wu Qiu, Mayank Goyal, Bijoy Menon, Andrew Demchuk","doi":"10.1136/svn-2024-003988","DOIUrl":"https://doi.org/10.1136/svn-2024-003988","url":null,"abstract":"<p><strong>Background: </strong>We aim to comprehensively assess and compare the predictive performance of haematoma expansion (HE) scores in a homogeneous cohort of acute intracerebral haemorrhage (ICH) patients.</p><p><strong>Methods: </strong>Existing scores for predicting HE in acute ICH patients were included and categorised by imaging modality: non-contrast CT (NCCT), single-phase CT angiography (sCTA) and multiphase CTA (mCTA). The predictive performance of the scores was evaluated with the c-statistic in a population of consecutive adult patients with acute ICH admitted to a tertiary care centre in Southern Alberta, Canada, between February 2012 and May 2020, investigated with a multimodal imaging protocol (NCCT, sCTA and mCTA). The primary outcome was HE (ICH volume growth ≥6 mL or ≥33%), and the secondary outcome was severe HE (ICH volume growth ≥12.5 mL or ≥66%). The DeLong test compared the best-performing scores from each imaging category.</p><p><strong>Results: </strong>16 HE scores were assessed (NCCT=8, sCTA=6 and mCTA=2) in 217 patients with a median age of 70 years (IQR=60-80), and 86 (39.6%) were females. 51 (23.5%) patients experienced HE and 35 (16.1%) had severe HE. The c-statistic for predicting HE ranged from 0.516 to 0.674 for NCCT-based scores, 0.627 to 0.725 for sCTA-based scores and 0.800 to 0.814 for mCTA-based score. The c-statistic for predicting severe HE ranged from 0.505 to 0.666 for NCCT scores, 0.651 to 0.740 for sCTA scores and 0.813 to 0.828 for mCTA scores. A statistically significant difference favouring mCTA over other imaging modalities in predicting both HE and severe HE was observed.</p><p><strong>Conclusions: </strong>Advanced imaging demonstrated a stepwise improvement in the predictive performance of HE scores. However, no existing score achieved excellent predictive performance (c-statistics ≥0.90) in our cohort, highlighting the need for further refinement.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804609","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":"Thrombus iodine-based perviousness is associated with recanalisation and functional outcomes in endovascular thrombectomy.","authors":"Chao Tian, Song Liu, Lejun Fu, Jingjing Guo, Chen Cao, Yu Sun, Tao Ren, Huiying Wang, Sifei Wang, Leilei Luo, Luotong Wang, Ming Wei, Shuang Xia, Song Jin, Tong Han, Nina Hao","doi":"10.1136/svn-2024-003661","DOIUrl":"10.1136/svn-2024-003661","url":null,"abstract":"<p><strong>Background: </strong>Dual-energy CT (DECT) provides several novel methods to assess thrombus perviousness. We aimed to evaluate whether the novel thrombus perviousness measured with DECT is associated with improved recanalisation and better functional outcomes in acute ischaemic stroke (AIS) patients with endovascular thrombectomy (EVT).</p><p><strong>Methods: </strong>108 AIS patients with middle cerebral artery occlusion who underwent DECT angiography on admission and received EVT treatment between April 2020 and September 2023 were retrospectively analysed. Thrombus attenuation increase (TAI) was evaluated on routine CT angiography and non-contrast CT, and DECT quantitative parameters of thrombus, including iodine concentration (IC) and normalised IC (NIC) were measured. Multivariable logistic regression analysis was used to evaluate the association of thrombus characteristics with arterial occlusive lesion scale and 90-day modified Rankin Scale.</p><p><strong>Results: </strong>NIC was significantly associated with successful recanalisation (OR 1.372 (95% CI 1.194 to 1.625); p<0.001) and good functional outcome (OR 1.252 (95% CI 1.114 to 1.446); p<0.001). NIC yielded higher performance, with area under curve (AUC) of 0.789 and 0.740, in the prediction of recanalisation and functional outcome than TAI (AUCs=0.635 and 0.592). Compared with low-level NIC thrombus, high-level NIC was associated with 11.4 and 15.4 times higher likelihood of successful recanalisation and good functional outcome. Moreover, NIC was a significant indicator to differentiate large artery atherosclerosis from cardioembolism stroke with high specificity and positive predictive value.</p><p><strong>Conclusions: </strong>Higher DECT-derived NIC is associated with increased odds of successful recanalisation and good functional outcome for EVT patients, and it yielded higher prediction performance than TAI.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505189","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":"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}