Journal of Investigative Medicine最新文献

{"title":"Safety and efficacy of GD-11 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.","authors":"Runhua Zhang, Gaifen Liu, Xingquan Zhao, Yilong Wang, Zixiao Li, Guofang Chen, Bo Liu, Yun Ling, Yongjun Wang, Shuya Li","doi":"10.1136/svn-2024-003338","DOIUrl":"https://doi.org/10.1136/svn-2024-003338","url":null,"abstract":"<p><strong>Background: </strong>GD-11, a novel brain cytoprotective drug, was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter. This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke (AIS).</p><p><strong>Methods: </strong>A double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 15 clinical sites in China. Patients aged 18-80 years with AIS within 48 hours were randomly assigned (1:1:1) to receive 160 mg GD-11, 80 mg GD-11 and placebo, two times a day for 10 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0-1 at 90 days after treatment. The safety outcome was any adverse events within 90 days.</p><p><strong>Results: </strong>From 17 November 2022 to 22 March 2023, a total of 80 patients in the 160 mg GD-11 group, 79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included. The proportion of an mRS score of 0-1 at day 90 was 77.5% in the 160 mg GD-11 group, 72.2% in the 80 mg GD-11 group and 67.5% in the placebo group. Though no significant difference was found (p=0.3671), a numerically higher proportion was observed in the GD-11 group, especially in the 160 mg GD-11 group. The incidence of adverse events was similar across the three groups (p=0.1992).</p><p><strong>Conclusion: </strong>GD-11 was safe and well-tolerated. A dosage of GD-11 160 mg two times a day was recommended for a large trial to investigate the efficacy.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898715","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":"Should patients with minor strokes be given thrombolytics?","authors":"Xun Wang, Yi Dong, Qiang Dong, David Wang","doi":"10.1136/svn-2024-003451","DOIUrl":"https://doi.org/10.1136/svn-2024-003451","url":null,"abstract":"<p><p>Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29-43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2(The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890664","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":"DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease (DR. BEYOND): the protocol of a multicentre randomised trial.","authors":"Dapeng Mo, Xu Tong, Xiaoqing Li, Chuan Qin, Yuesong Pan, Sheng Guan, Zhongrong Miao","doi":"10.1136/svn-2024-003259","DOIUrl":"https://doi.org/10.1136/svn-2024-003259","url":null,"abstract":"<p><strong>Background: </strong>Although endovascular stenting is considered an effective and safe therapeutic option for symptomatic intracranial atherosclerotic disease (sICAD), an elevated rate of restenosis remains an important issue for the conventional bare-metal stent (BMS). Recent evidence from observational studies suggests that applying drug-coated balloons (DCB) in sICAD may decrease restenosis occurrence. Additional large randomised studies are warranted to provide firmer evidence and to determine which patients would benefit most from DCB.</p><p><strong>Aim: </strong>To design a randomised trial to examine DCB angioplasty (Taijieweiye intracranial paclitaxel-coated balloon catheter) versus BMS stenting (Wingspan intracranial stent system) in patients with sICAD.</p><p><strong>Design: </strong>This is a multicentre, prospective, randomised, open-label, blinded end-point study to assess whether DCB angioplasty reduces the risk of restenosis compared with BMS stenting in sICAD patients with high-grade stenosis (≥70%-99%). Our goal is to randomly assign 198 eligible individuals at a 1:1 ratio to undergo DCB angioplasty (intervention group) or BMS stenting (control group).</p><p><strong>Outcome: </strong>The primary efficacy outcome is restenosis at 6 months post treatment, that is, >50% stenosis in or within 5 mm of the treated segment and >20% absolute luminal loss. The primary safety outcome is stroke or death within 30 days post treatment.</p><p><strong>Discussion: </strong>The DRug-coated Balloon for Endovascular treatment of sYmptOmatic intracraNial stenotic Disease trial aims to produce strong evidence on the efficacy and safety of DCB angioplasty as a promising therapeutic option for sICAD cases with high-grade stenosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753123","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":"Determinants of prehospital and in-hospital delay in patients with symptomatic carotid stenosis and their influence on the outcome after elective carotid endarterectomy.","authors":"Felix Kirchhoff, Christoph Knappich, Michael Kallmayer, Bianca Bohmann, Vanessa Lohe, Pavlos Tsantilas, Shamsun Naher, Hans-Henning Eckstein, Andreas Kühnl","doi":"10.1136/svn-2024-003098","DOIUrl":"https://doi.org/10.1136/svn-2024-003098","url":null,"abstract":"<p><strong>Background: </strong>This study analyses the determinants of prehospital (index event to admission) and in-hospital delay (admission to carotid endarterectomy (CEA)). In addition, the analysis addresses the association between prehospital or in-hospital delay and outcomes after CEA for symptomatic patients in German hospitals.</p><p><strong>Materials and methods: </strong>This retrospective analysis is based on the nationwide German statutory quality assurance database. 55 437 patients were included in the analysis. Prehospital delay was grouped as follows: 180-15, 14-8, 7-3, 2-0 days or 'in-hospital index event'. In-hospital delay was divided into: 0-1, 2-3 and >3 days. The primary outcome event (POE) was in-hospital stroke or death. Univariate and multivariable regression analyses were performed for statistical analysis. The slope of the linear regression line is given as the β-value, and the rate parameter of the logistic regression is given as the adjusted OR (aOR).</p><p><strong>Results: </strong>Prehospital delay was 0-2 days in 34.9%, 3-14 days in 29.5% and >14 days in 18.6%. Higher age (β=-1.08, p<0.001) and a more severe index event (transitory ischaemic attack: β=-4.41, p<0.001; stroke: β=-6.05, p<0.001, Ref: amaurosis fugax) were determinants of shorter prehospital delay. Higher age (β=0.28, p<0.001) and female sex (β=0.09, p=0.014) were associated with a longer in-hospital delay. Index event after admission (aOR 1.23, 95% CI: 1.04 to 1.47) and an intermediate in-hospital delay of 2-3 days (aOR 1.15, 95% CI: 1.00 to 1.33) were associated with an increased POE risk.</p><p><strong>Conclusions: </strong>This study revealed that older age, higher American Society of Anesthesiology (ASA) stage, increasing severity of symptoms and ipsilateral moderate stenosis were associated with shorter prehospital delay. Non-specific symptoms were associated with a longer prehospital delay. Regarding in-hospital delay, older age, higher ASA stage, contralateral occlusion, preprocedural examination by a neurologist and admission on Fridays or Saturdays were associated with lagged treatment. A very short (<2 days) prehospital and intermediate in-hospital delay (2-3 days) were associated with increased risk of perioperative stroke or death.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538820","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":"Healthy lifestyles are associated with alleviating the single-nucleotide polymorphism-based genetic risks of ischaemic stroke, intracerebral haemorrhage and myocardial infarction.","authors":"Jingru Wang, Zhenqiu Liu, Chengxin Hu, Renjia Zhao, Dongliang Zhu, Yijing Xie, Pengyan Zhang, Mei Cui, Kelin Xu, Genming Zhao, Li Jin, Xingdong Chen, Chen Suo, Yanfeng Jiang","doi":"10.1136/svn-2024-003257","DOIUrl":"https://doi.org/10.1136/svn-2024-003257","url":null,"abstract":"<p><strong>Background: </strong>Both genetic and lifestyle factors contribute to myocardial infarction (MI) and stroke, including ischaemic stroke (IS) and intracerebral haemorrhage (ICH). We explored how and the extent to which a healthy lifestyle, by considering a comprehensive list, could counteract the genetic risk of those diseases, respectively.</p><p><strong>Methods: </strong>315 044 participants free of stroke and MI at baseline were identified from the UK Biobank. Genetic risk scores (GRS) for those diseases were constructed separately and categorised as low, intermediate and high by tertile. Lifestyle risk scores (LRS) were constructed separately using smoking, alcohol intake, physical activity, dietary patterns and sleep patterns. Similarly, participants were categorised into low, intermediate and high LRS. The data were analysed using Cox proportional hazard models.</p><p><strong>Results: </strong>Over a median follow-up of 12.8 years, 4642, 1046 and 9485 participants developed IS, ICH and MI, respectively. Compared with participants with low levels of GRS and LRS, the HRs of those with high levels of GRS and LRS were 3.45 (95% CI 2.71 to 4.41), 2.32 (95% CI 1.40 to 3.85) and 4.89 (95% CI 4.16 to 5.75) for IS, ICH and MI, respectively. Moreover, among participants with high GRS, the standardised 14-year rates of IS events were 4.40% (95% CI 3.45% to 5.36%) among those with high LRS. In contrast, it is only 1.78% (95% CI 1.63% to 1.94%) among those with low LRS. Similarly for MI, the high LRS group had standardised rates of 8.60% (95% CI 7.38% to 9.81%), compared with 3.34% (95% CI 3.12% to 3.56%) in low LRS. Among the high genetic risk group of ICH, the rate is reduced by about half compared low LRS to high LRS, although the rate was low for both (0.36% (95% CI 0.31% to 0.42%) and 0.71% (95% CI 0.36% to 1.05%), respectively).</p><p><strong>Conclusion: </strong>Healthy lifestyles were substantially associated with a reduction in the risk of IS, ICH and MI and attenuated the genetic risk of IS, ICH and MI by at least half, respectively.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460176","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":"Incidence and predictors of futile recanalisation after endovascular therapy in acute vertebrobasilar artery occlusion patients: insight from the ANGEL-ACT registry.","authors":"Dapeng Sun, Xinguang Yang, Xiaochuan Huo, Raynald -, Baixue Jia, Xu Tong, Anxin Wang, Ning Ma, Feng Gao, Dapeng Mo, Zhongrong Miao","doi":"10.1136/svn-2022-002185","DOIUrl":"10.1136/svn-2022-002185","url":null,"abstract":"<p><strong>Objectives: </strong>To identify the occurrence rate and predictors of futile recanalisation after endovascular therapy (EVT) for acute vertebrobasilar artery occlusion (VBAO).</p><p><strong>Methods: </strong>Participants of the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischaemic Stroke (ANGEL-ACT) registry were selected for the analysis. Futile recanalisation was defined as patients did not achieve a 90-day good outcome (modified Rankin Scale ≤3) despite successful recanalisation (modified Treatment in Cerebral Ischaemia Scale ≥2b) after the procedure. Multivariable logistic regression analysis was conducted to find independent predictors of futile recanalisation in VBAO patients undergoing EVT.</p><p><strong>Results: </strong>Three hundred and fifteen patients with VBAO who achieved successful recanalisation after EVT were included in current analysis, of whom, 155 (49.2%) suffered futile recanalisation, and 160 achieved effective recanalisation. After the multivariable analysis, we found admission National Institutes of Health Stroke Scale (NIHSS) ≥19 (OR 4.81, 95% CI 2.76 to 8.39, p<0.001), platelet-lymphocyte ratio (PLR) ≥162.2 (OR 1.93, 95% CI 1.14 to 3.27, p=0.001), onset-to-puncture time (OTP) ≥334 min (OR 2.15, 95% CI 1.25 to 3.68, p=0.005) and use of general anesthesia (GA) (OR 1.87, 95% CI 1.09 to 3.22, p=0.024) were associated with futile recanalisation.</p><p><strong>Conclusions: </strong>Futile recanalisation after EVT occurred 49.2% of VBAO patients in the ANGEL-ACT registry. NIHSS≥19, PLR≥162.2, OTP≥334 min and use of GA were independent predictors of futile recanalisation.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41216799","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":"Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial.","authors":"Tianzhu Chen, Tianyan Chen, Yong Zhang, Kang Wu, Yihuai Zou","doi":"10.1136/svn-2023-002785","DOIUrl":"10.1136/svn-2023-002785","url":null,"abstract":"<p><strong>Background: </strong>Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity.</p><p><strong>Methods: </strong>IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation.</p><p><strong>Results: </strong>46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R²=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event.</p><p><strong>Conclusions: </strong>The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713206","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":"Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm.","authors":"Hae Rang Kim, Min Jeoung Kim, Sunyeup Kim, Myung Soo Chang, Dong Joon Kim, Byung Moon Kim, Keun Young Park, Yong Bae Kim, Christopher Seungkyu Lee, Suk Ho Byeon, Sung Soo Kim, Seung Won Lee, Yong Joon Kim","doi":"10.1136/svn-2023-002563","DOIUrl":"10.1136/svn-2023-002563","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA).</p><p><strong>Methods: </strong>Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs.</p><p><strong>Results: </strong>In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping.</p><p><strong>Conclusions: </strong>Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105208","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":"New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1.","authors":"Masayuki Otani, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Yo Oguma, Keisuke Sasaki, Shintaro Katahira, Ryohei Terai, Rie Ryoke, Hiroi Nonaka, Ryuta Kawashima, Yoshikatsu Saiki, Mari Dezawa","doi":"10.1136/svn-2023-002962","DOIUrl":"https://doi.org/10.1136/svn-2023-002962","url":null,"abstract":"<p><strong>Background: </strong>The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.</p><p><strong>Objective: </strong>We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.</p><p><strong>Methods: </strong>In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.</p><p><strong>Results: </strong>The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.</p><p><strong>Conclusions: </strong>Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437622","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":"Is intraprocedural intravenous aspirin safe for patients who require emergent extracranial stenting during mechanical thrombectomy?","authors":"Adam Ingleton, Marko Raseta, Rui-En Chung, Kevin Jun Hui Kow, Jake Weddell, Sanjeev Nayak, Changez Jadun, Zafar Hashim, Noman Qayyum, Phillip Ferdinand, Indira Natarajan, Christine Roffe","doi":"10.1136/svn-2022-002267","DOIUrl":"10.1136/svn-2022-002267","url":null,"abstract":"<p><strong>Background: </strong>Intraoperative antiplatelet therapy is recommended for emergent stenting during mechanical thrombectomy (MT). Most patients undergoing MT are also given thrombolysis. Antiplatelet agents are contraindicated within 24 hours of thrombolysis. We evaluated outcomes and complications of patients stented with and without intravenous aspirin during MT.</p><p><strong>Methods: </strong>All patients who underwent emergent extracranial stenting during MT at the Royal Stoke University Hospital, UK between 2010 and 2020, were included. Patients were thrombolysed before MT, unless contraindicated. Aspirin 500 mg intravenously was given intraoperatively at the discretion of the operator. Symptomatic intracranial haemorrhage (sICH) and the National Institutes for Health Stroke Scale score (NIHSS) were recorded at 7 days, and mortality and functional recovery (modified Rankin Scale: mRS ≤2) at 90 days.</p><p><strong>Results: </strong>Out of 565 patients treated by MT 102 patients (median age 67 IQR 57-72 years, baseline median NIHSS 18 IQR 13-23, 76 (75%) thrombolysed) had a stent placed. Of these 49 (48%) were given aspirin and 53 (52%) were not. Patients treated with aspirin had greater NIHSS improvement (median 8 IQR 1-16 vs median 3 IQR -9-8 points, p=0.003), but there were no significant differences in sICH (2/49 (4%) vs 9/53 (17%)), mRS ≤2 (25/49 (51%) vs 19/53 (36%)) and mortality (10/49 (20%) vs 12/53 (23%)) with and without aspirin. NIHSS improvement (median 12 IQR 4-18 vs median 7 IQR -7-10, p=0.01) was greater, and mortality was lower (4/33 (12%) vs 6/15 (40%), p=0.05) when aspirin was combined with thrombolysis, than for aspirin alone, with no increase in bleeding.</p><p><strong>Conclusion: </strong>Our findings based on registry data derived from routine clinical care suggest that intraprocedural intravenous aspirin in patients undergoing emergent stenting during MT does not increase sICH and is associated with good clinical outcomes, even when combined with intravenous thrombolysis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155451","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}