Journal of Investigative Medicine最新文献

{"title":"Thrombolysis for ischaemic stroke despite direct oral anticoagulation.","authors":"Jan C Purrucker, Thomas R Meinel, Duncan Wilson, Ying Xian, Teddy Y Wu, David J Seiffge","doi":"10.1136/svn-2023-002727","DOIUrl":"10.1136/svn-2023-002727","url":null,"abstract":"<p><p>Intravenous thrombolysis is not recommended in anticoagulated patients receiving direct oral anticoagulants (DOACs) and a recent intake within the last 48 hours in US and European guidelines. However, three observational studies now suggest safety of thrombolysis in patients with recent intake of DOACs, and thus support previous experimental data. In this perspective, the current evidence and practical consequences are discussed.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"464-466"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724555","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":"Real-world analysis of two ischaemic stroke and TIA systolic blood pressure goals on 12-month mortality and recurrent vascular events.","authors":"Jason J Sico, Xin Hu, Laura J Myers, Deborah Levine, Dawn M Bravata, Greg W Arling","doi":"10.1136/svn-2023-002759","DOIUrl":"10.1136/svn-2023-002759","url":null,"abstract":"<p><strong>Introduction: </strong>Whether obtaining the more intensive goal systolic blood pressure (SBP) of <130 mm Hg, rather than a less intensive SBP goal of <140 mm Hg poststroke/transient ischaemic attack (TIA) is associated with incremental mortality and recurrent vascular event benefit is largely unexplored using real-world data. Lowering SBP excessively may result in poorer outcomes.</p><p><strong>Methods: </strong>This is a retrospective cohort study of 26 368 Veterans presenting to a Veterans Administration Medical Center (VAMC) with a stroke/TIA between October 2015 and July 2018. Patients were excluded from the study if they had missing or extreme BP values, receiving dialysis or palliative care, left against medical advice had a cancer diagnosis, were cared for in a VAMC enrolled in a stroke/TIA quality improvement initiative, died or had a cerebrovascular or cardiovascular event within 90 days after their index stroke/TIA. The analytical sample included 12 337 patients. Average SBP during 90 days after discharge was assessed in categories (≤105 mm Hg, 106-115 mm Hg, 116-130 mm Hg, 131-140 mm Hg and >140 mm Hg). Separate multivariable Cox proportional hazard regressions were used to examine the relationship between average SBP groups and time to: (1) mortality and (2) any recurrent vascular event, from 90 days to up to 365 days after discharge from the index emergency department visit or inpatient admission.</p><p><strong>Results: </strong>Compared with those with SBP>140 mm Hg, patients with SBP between 116 and 130 mm Hg had a significantly lower risk of recurrent stroke/TIA (HR 0.77, 95% CI 0.60 to 0.99) but not cardiovascular events. Patients with SBP lower than 105 mm Hg, compared with those with >140 mm Hg demonstrated a statistically significant higher risk of death (HR 2.07, 95% CI 1.43 to 3.00), but no statistical differences were found in other SBP groups.</p><p><strong>Discussion: </strong>Data support a more intensive SBP goal to prevent recurrent cerebrovascular events among stroke/TIA patients by 90 days poststroke/TIA compared with less intensive goal. Very low SBPs were associated with increased mortality risk.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"519-529"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404873","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":"Discontinuation of antiplatelet therapy after stent-assisted coil embolisation of cerebral aneurysm: a nationwide cohort study.","authors":"Minyoul Baik, Jimin Jeon, Jinkwon Kim, Joonsang Yoo","doi":"10.1136/svn-2023-002882","DOIUrl":"10.1136/svn-2023-002882","url":null,"abstract":"<p><strong>Introduction: </strong>Stent-assisted coil embolisation (SACE) for the treatment of unruptured cerebral aneurysms has been increasingly used. Long-term advantages of antiplatelet therapy (APT) post-SACE treatment are still not well understood. We investigated the long-term effects of APT on clinical prognosis after SACE.</p><p><strong>Patients and methods: </strong>We conducted a retrospective study using nationwide health insurance claims data from South Korea, including patients with cerebral aneurysm treated with SACE from January 2009 to December 2020. The study outcomes consisted of the occurrence of cerebral infarction and major haemorrhage. To evaluate the impact of APT, we employed a multivariable time-dependent Cox proportional hazards regression model for each of the three distinct periods: 1-12 months, 12-24 months and >24 months after SACE.</p><p><strong>Results: </strong>This study included 17 692 unruptured cerebral aneurysm patients treated with SACE. During the mean follow-up of 4.2 years, there were 379 (2.1%) patients with cerebral infarction and 190 (1.1%) patients with major haemorrhage. The percentage of patients receiving APT was 79.5% at 1 year, which gradually decreased to 58.3% at 2 years after SACE. APT was beneficial in preventing cerebral infarction within 12 months after SACE (adjusted HR (aHR) 0.56; 95% CI, 0.35 to 0.89; p=0.014). After 12 months, this association was not evident. APT increased the risk of haemorrhage after 24 months (aHR 1.76; 95% CI 1.11 to 2.87; p=0.016).</p><p><strong>Discussion and conclusion: </strong>Our findings suggest that in patients with unruptured cerebral aneurysm treated with SACE, the reasonable duration of APT for preventing cerebral infarction might be 1 year after SACE.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"560-567"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576687","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":"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}