Journal of Investigative Medicine最新文献

{"title":"Safety and efficacy of glibenclamide on cerebral oedema following aneurysmal subarachnoid haemorrhage: a randomised, double-blind, placebo-controlled clinical trial.","authors":"Xuebing Feng, Tongyu Zhang, Ning Wang, Xin Qu, Meng Qi, Hao Zhao, Hongqi Zhang, Yueqiao Xu","doi":"10.1136/svn-2023-002892","DOIUrl":"10.1136/svn-2023-002892","url":null,"abstract":"<p><strong>Background: </strong>Glibenclamide has garnered attention due to its multifaceted neuroprotective effects in cases of acute central nervous system injury. We initiated a trial to explore the effectiveness and safety of a high dose of glibenclamide in the management of cerebral oedema following aneurysmal subarachnoid haemorrhage (aSAH).</p><p><strong>Methods: </strong>This trial constituted a single-centre, randomised clinical study. Half of the 56 patients assigned to the glibenclamide group received 15 mg of glibenclamide tablets daily for 10 days (5 mg, three times/day). The primary outcome was the proportion of patients achieving the subarachnoid haemorrhage early brain oedema score dichotomy (defined as Subarachnoid Haemorrhage Early Brain Oedema Score 0-2) at the 10-day postmedication. The secondary outcome of cerebral oedema was the concentration of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) in the plasma and cerebrospinal fluid.</p><p><strong>Results: </strong>We enrolled 56 patients diagnosed with aSAH, who were admitted to the neurosurgery intensive care unit between 22 August 2021 and 25 April 2023. The primary outcome revealed that the glibenclamide group exhibited a notably higher proportion of mild cerebral oedema in comparison to the placebo group (60.7% vs 42.9%, adjusted OR: 4.66, 95% CI 1.14 to 19.10, p=0.032). Furthermore, the concentration of SUR1-TRPM4 in the cerebrospinal fluid of the glibenclamide group was significantly higher than the placebo group (p=0.0002; p=0.026), while the plasma TRPM4 concentration in the glibenclamide group was significantly lower than the placebo group (p=0.001).</p><p><strong>Conclusion: </strong>Oral administration of high-dose glibenclamide notably reduced radiological assessment of cerebral oedema after 10 days of medication. Significant alterations were also observed in the concentration of SUR1-TRPM4 in plasma and cerebrospinal fluid. However, it is worth noting that glibenclamide was associated with a higher incidence of hypoglycaemia. Larger trials are warranted to evaluate the potential benefits of glibenclamide in mitigating swelling and then improving neurological function.</p><p><strong>Trial registration number: </strong>ChiCTR2100049908.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"530-540"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404883","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":"Treatment practice of vasospasm during endovascular thrombectomy: an international survey.","authors":"Jessica Jesser, Thanh Nguyen, Adam A Dmytriw, Hiroshi Yamagami, Zhongrong Miao, Louisa Johanna Sommer, Andrea Stockero, Johannes Alex Rolf Pfaff, Johanna Ospel, Mayank Goyal, Aman B Patel, Vitor Mendes Pereira, Uta Hanning, Lukas Meyer, Wim H van Zwam, Martin Bendszus, Martin Wiesmann, Markus Möhlenbruch, Charlotte Sabine Weyland","doi":"10.1136/svn-2023-002788","DOIUrl":"10.1136/svn-2023-002788","url":null,"abstract":"<p><strong>Background and aim: </strong>The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT.</p><p><strong>Methods: </strong>We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI's opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.</p><p><strong>Results: </strong>In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient's outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p<0.001), as well as extracranial vasospasm (61.4% vs 36.5%, p<0.001) and intracranial medium-vessel vasospasm (27.1% vs 11.2%, p<0.001), compared with group 2. In case of a large-vessel vasospasm and residual and amenable medium-vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p<0.001).</p><p><strong>Conclusion: </strong>There is disagreement among NIs about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"490-496"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075627","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":"Association between Life's Essential 8 and Cerebral Small Vessel Disease.","authors":"Dandan Liu, Xueli Cai, Yingying Yang, Suying Wang, Lerong Mei, Jing Jing, Shan Li, Mengxing Wang, Yun Chen, Xia Meng, Tiemin Wei, Yongjun Wang, Yilong Wang, Yuesong Pan","doi":"10.1136/svn-2023-002628","DOIUrl":"10.1136/svn-2023-002628","url":null,"abstract":"<p><strong>Background: </strong>Given that associations of Life's Essential 8 (LE8) and cerebral small vessel disease (CSVD) or its imaging markers were unclear, we examined relationship between them.</p><p><strong>Methods: </strong>The cross-sectional study included community residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. We calculated the total LE8 score, medical LE8 score and behavioural score, and categorised them into low (<60), moderate (60-79) or high (≥80) group. MRI markers included lacunes, white matter hyperintensities (WMH), enlarged perivascular spaces in basal ganglia (BG-EPVS) and cerebral microbleeds (CMB). In respect of, total CSVD score (0-4 points), WMH, lacunes or CMB were categorised as two grades, and BG-EPVS (N>10) was allocated one point. Based on modified total CSVD score (0-6 points), WMH or CMB was modified to three grades, and BG-EPVS (N>20) was allocated one point.</p><p><strong>Results: </strong>Among 3061 participants in this study, 1424 (46.5%) were male. Higher LE8 score was associated with lower total CSVD score (moderate vs low: cOR 0.78, 95% CI 0.63 to 0.96; high vs low: cOR 0.44, 95% CI 0.33 to 0.59), and the medical score was inversely related to the total CSVD score. Furthermore, the medical score was inversely related to odds of WMH (p<0.05), modified WMH (p<0.05), lacunes (p<0.05) or BG-EPVS (p<0.05), and the behavioural score were inversely related to the odds of lacunes and BG-EPVS.</p><p><strong>Conclusions: </strong>Higher LE8 score which indicates better cardiovascular status was associated with lower burden of CSVD and its MRI markers. Longitudinal studies are needed to examine the causality.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"481-489"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292166","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":"Efficacy and safety of dual antiplatelet therapy in the elderly for stroke prevention: a subgroup analysis of the CHANCE-2 trial.","authors":"Xinmiao Zhang, Jing Jing, Anxin Wang, Xuewei Xie, S Claiborne Johnston, Hao Li, Philip M Bath, Qin Xu, Jinxi Lin, Yilong Wang, Xingquan Zhao, Zixiao Li, Yong Jiang, Liping Liu, Weifeng Chen, Xuhai Gong, Jianhua Li, Xinsheng Han, Xia Meng, Yongjun Wang","doi":"10.1136/svn-2023-002450","DOIUrl":"10.1136/svn-2023-002450","url":null,"abstract":"<p><strong>Objectives: </strong>Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited, especially those elder than 80 years. This study aimed to explore the efficacy and safety of dual antiplatelet therapy (DAPT) in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events-II (CHANCE-2) trial.</p><p><strong>Methods: </strong>CHANCE-2 was a randomised, double-blind, placebo-controlled trial in China involving patients with high-risk transient ischaemic attack or minor stroke with CYP2C19 loss-of-function alleles. In our substudy, all enrolled patients were stratified by age: old-old (≥80 years), young-old (65-80 years) and younger (<65 years). The primary outcomes were stroke recurrence and moderate to severe bleeding within 90 days, respectively.</p><p><strong>Results: </strong>Of all the 6412 patients, 406 (6.3%) were old-old, 2755 (43.0%) were young-old and 3251 (50.7%) were younger. Old-old patients were associated with higher composite vascular events (HR 1.41, 95% CI 1.00 to 1.98, p=0.048), disabling stroke (OR 2.43, 95% CI 1.52 to 3.88, p=0.0002), severe or moderate bleeding (HR 8.40, 95% CI 1.95 to 36.21, p=0.004) and mortality (HR 7.56, 95% CI 2.23 to 25.70, p=0.001) within 90 days. Ticagrelor-aspirin group was associated with lower risks of stroke recurrence within 90 days in younger patients (HR 0.68, 95% CI 0.51 to 0.91, p=0.008), which was no differences in old-old patients.</p><p><strong>Conclusion: </strong>Elderly patients aged over 80 in CHANCE-2 trial had higher risks of composite vascular events, disabling stroke, severe or moderate bleeding and mortality within 90 days. Genotype-guided DAPT might not be as effective in old-old patients as in younger ones.</p><p><strong>Trial registration number: </strong>NCT04078737.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"541-550"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576622","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":"Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE): rationale and design of a multicentre, prospective, randomised, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial.","authors":"Shuya Li, Hong-Qiu Gu, Hongguo Dai, Guozhi Lu, Yongjun Wang","doi":"10.1136/svn-2023-003035","DOIUrl":"10.1136/svn-2023-003035","url":null,"abstract":"<p><strong>Background and purpose: </strong>Reteplase is the third generation of alternative thrombolytic agent. We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible patients with acute ischaemic stroke.</p><p><strong>Methods and design: </strong>Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE) trial is a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled phase 3 non-inferiority trial. A total of 1412 eligible patients will be randomly assigned to receive either reteplase at a dose of 18 mg+ 18 mg or alteplase 0.9 mg/kg at a ratio of 1:1. An independent data monitoring committee will review the trail's progress and safety data.</p><p><strong>Study outcomes: </strong>The primary efficacy outcome of this study is proportion of individuals attaining an excellent functional outcome, defined as modified Rankin Scale (mRS) 0-1 at 90 days. The secondary efficacy outcomes encompass favourable functional outcome defined as mRS 0-2, major neurological improvement on the National Institutes of Health Stroke Scale, ordinal distribution of mRS and Barthel Index score of at least 95 points at 90 days. The primary safety outcomes are symptomatic intracranial haemorrhage at 36 hours within 90 days.</p><p><strong>Discussion: </strong>The RAISE trial will provide crucial insights into the selection of thrombolytic agents for stroke thrombolysis.</p><p><strong>Trial registration number: </strong>NCT05295173.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"568-573"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576624","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":"Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice.","authors":"Lin Qi, Cheng Wang, Lidong Deng, Jia-Ji Pan, Qian Suo, Shengju Wu, Lin Cai, Xudong Shi, Junfeng Sun, Yongting Wang, Yaohui Tang, Weibao Qiu, Guo-Yuan Yang, Jixian Wang, Zhijun Zhang","doi":"10.1136/svn-2023-002614","DOIUrl":"10.1136/svn-2023-002614","url":null,"abstract":"<p><strong>Background: </strong>Low-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms of neurological repair and remodelling after LIFUS in ischaemic stroke are unclear.</p><p><strong>Methods: </strong>Ultrasound stimulation was treated in adult male mice 7 days after transient middle cerebral artery occlusion. Angiogenesis was measured by laser speckle imaging and histological analyses. Electromyography and fibre photometry records were used for synaptogenesis. Brain atrophy volume and neurobehaviour were assessed 0-14 days after ischaemia. iTRAQ proteomic analysis was performed to explore the differentially expressed protein. scRNA-seq was used for subcluster analysis of astrocytes. Fluorescence in situ hybridisation and Western blot detected the expression of HMGB1 and CAMK2N1.</p><p><strong>Results: </strong>Optimal ultrasound stimulation increased cerebral blood flow, and improved neurobehavioural outcomes in ischaemic mice (p<0.05). iTRAQ proteomic analysis revealed that the expression of HMGB1 increased and CAMK2N1 decreased in the ipsilateral hemisphere of the brain at 14 days after focal cerebral ischaemia with ultrasound treatment (p<0.05). scRNA-seq revealed that this expression pattern belonged to a subcluster of astrocytes after LIFUS in the ischaemic brain. LIFUS upregulated HMGB1 expression, accompanied by VEGFA elevation compared with the control group (p<0.05). Inhibition of HMGB1 expression in astrocytes decreased microvessels counts and cerebral blood flow (p<0.05). LIFUS reduced CAMK2N1 expression level, accompanied by increased extracellular calcium ions and glutamatergic synapses (p<0.05). CAMK2N1 overexpression in astrocytes decreased dendritic spines, and aggravated neurobehavioural outcomes (p<0.05).</p><p><strong>Conclusion: </strong>Our results demonstrated that LIFUS promoted angiogenesis and synaptogenesis after focal cerebral ischaemia by upregulating HMGB1 and downregulating CAMK2N1 in a subcluster of astrocytes, suggesting that LIFUS activated specific astrocyte subcluster could be a key target for ischaemic brain therapy.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"505-518"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404872","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":"Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial.","authors":"Xin Cheng, Lan Hong, Leonid Churilov, Longting Lin, Yifeng Ling, Jin Zhang, Jianhong Yang, Yu Geng, Danhong Wu, Xueyuan Liu, Xiaoyu Zhou, Yuwu Zhao, Qijin Zhai, Liandong Zhao, Yangmei Chen, Ying Guo, Xiaofei Yu, Fan Gong, Yi Sui, Gang Li, Lumeng Yang, Hong-Qiu Gu, Yilong Wang, Mark Parsons, Qiang Dong","doi":"10.1136/svn-2023-002820","DOIUrl":"10.1136/svn-2023-002820","url":null,"abstract":"<p><strong>Background: </strong>The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window.</p><p><strong>Methods: </strong>The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis.</p><p><strong>Results: </strong>A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design.</p><p><strong>Discussion: </strong>Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"551-559"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576626","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":"Anti-stroke biologics: from recombinant proteins to stem cells and organoids.","authors":"Zhu-Wei Miao, Zhi Wang, Si-Li Zheng, Shu-Na Wang, Chao-Yu Miao","doi":"10.1136/svn-2023-002883","DOIUrl":"10.1136/svn-2023-002883","url":null,"abstract":"<p><p>The use of biologics in various diseases has dramatically increased in recent years. Stroke, a cerebrovascular disease, is the second most common cause of death, and the leading cause of disability with high morbidity worldwide. For biologics applied in the treatment of acute ischaemic stroke, alteplase is the only thrombolytic agent. Meanwhile, current clinical trials show that two recombinant proteins, tenecteplase and non-immunogenic staphylokinase, are most promising as new thrombolytic agents for acute ischaemic stroke therapy. In addition, stem cell-based therapy, which uses stem cells or organoids for stroke treatment, has shown promising results in preclinical and early clinical studies. These strategies for acute ischaemic stroke mainly rely on the unique properties of undifferentiated cells to facilitate tissue repair and regeneration. However, there is a still considerable journey ahead before these approaches become routine clinical use. This includes optimising cell delivery methods, determining the ideal cell type and dosage, and addressing long-term safety concerns. This review introduces the current or promising recombinant proteins for thrombolysis therapy in ischaemic stroke and highlights the promise and challenges of stem cells and cerebral organoids in stroke therapy.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"467-480"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576685","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":"Trendelenburg position for acute anterior circulation ischaemic stroke with large artery atherosclerosis aetiology (HOPES 3): rationale and design.","authors":"Xiaoqiu Li, Zhenni Guo, Lu Wang, Yue Wang, Thanh Nguyen, Yi Yang, Hui-Sheng Chen","doi":"10.1136/svn-2023-002868","DOIUrl":"10.1136/svn-2023-002868","url":null,"abstract":"<p><strong>Rationale: </strong>The effect of the head position as a non-pharmacological therapy on acute ischaemic stroke (AIS) remains inconclusive. Our recent Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis (HOPES 2) suggested the safety, feasibility and potential benefit of the head-down position (HDP) in AIS.</p><p><strong>Aim: </strong>To investigate the benefit of HDP in acute moderate ischaemic stroke patients with large artery atherosclerosis (LAA).</p><p><strong>Sample size estimates: </strong>Based on a two-sided 0.05 level of significance, 600 patients are expected to yield the superiority hypothesis with 80% power, stratified by age, sex, history of diabetes, baseline systolic blood pressure, location of index vessel, National Institutes of Health Stroke Scale Score at randomisation, onset to randomisation time, progression to moderate neurological deficit due to early neurological deterioration and degree of responsible vessel stenosis.</p><p><strong>Design: </strong>Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis(HOPES 3) is a prospective, randomised, open-label, blinded endpoint and multicentre study. Eligible patients who had an ischaemic stroke will be randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg plus standard medical care in compliance with national guidelines, or control group only receiving standard medical care in compliance with national guidelines.</p><p><strong>Outcome: </strong>The primary outcome is favourable functional outcome, defined as modified Rankin Scale 0-2 at 90 days. Safety outcomes are HDP-related adverse events. All outcomes will have blinded assessment and will be analysed on the intention-to-treat basis.</p><p><strong>Conclusions: </strong>The results of HOPES 3 will provide evidence for the effect of HDP in acute moderate ischaemic stroke patients with LAA within 24 hours of onset or in patients with progression from mild neurological deficit within 24 hours.</p><p><strong>Trial registration number: </strong>NCT06010641.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"574-579"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724556","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":"Characteristics, temporal trends and outcomes of intravenous thrombolysis in Chinese patients aged>80 years who had a stroke.","authors":"Changsheng Li, Yingyu Jiang, Hong-Qiu Gu, Meng Wang, Zimo Chen, Xin Yang, Qi Zhou, Xia Meng, Chunjuan Wang, Zixiao Li","doi":"10.1136/svn-2024-003427","DOIUrl":"https://doi.org/10.1136/svn-2024-003427","url":null,"abstract":"<p><strong>Background and purpose: </strong>To date, no large cohort study has investigated the effects of intravenous thrombolysis (IVT) in Chinese patients aged over 80 years who had a stroke. This study aimed to assess the trends in the use of alteplase, the clinical characteristics and the outcomes of Chinese patients aged above 80 years who had an acute ischaemic stroke.</p><p><strong>Methods: </strong>Data for this analysis were obtained from the China Stroke Center Alliance programme, a nationwide, multicentre, prospective registry encompassing 1751 hospitals across 31 provinces, covering the period from 1 January 2018 to 14 December 2022. The primary outcome was defined as a modified Rankin Scale (mRS) Score of 0-2 at discharge. Secondary outcomes included an mRS Score of 0-1 and independent ambulation on discharge. Safety outcomes assessed were in-hospital mortality and symptomatic intracranial haemorrhage (sICH).</p><p><strong>Results: </strong>Out of 30 902 patients over 80 years old who qualified for thrombolysis, 8673 (median age (IQR), 84 (82-87) years) received alteplase treatment. Patients administered alteplase demonstrated improved short-term functional outcomes, such as an mRS Score of 0-2 (adjusted OR (aOR) 1.12, 95% CI, 1.06 to 1.18, p<0.001), an mRS Score of 0-1 (aOR 1.14, 95% CI, 1.08 to 1.19, p<0.001) and independent ambulation at discharge (aOR 1.14, 95% CI, 1.08 to 1.20, p<0.001). Moreover, no significant increase was observed in the risk of in-hospital mortality (aOR 1.12, 95% CI, 0.93 to 1.35; p=0.23). However, the risk of sICH was significantly higher among patients treated with alteplase (aOR 3.22, 95% CI, 2.77 to 3.75; p<0.001).</p><p><strong>Conclusions: </strong>IVT with alteplase in elderly patients who had a stroke resulted in improved short-term functional outcomes without elevating the risk of in-hospital mortality. Nonetheless, this population remains at a higher risk of sICH.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559176","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}