{"title":"Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.","authors":"Xiaotao Su, Tiemei Li, Yuge Wang, Lei Wei, Banghao Jian, Xinmei Kang, Mengyan Hu, Chunyi Li, Shisi Wang, Danli Lu, Shishi Shen, Huipeng Huang, Yuxin Liu, Xiaohui Deng, Bingjun Zhang, Wei Cai, Zhengqi Lu","doi":"10.1136/svn-2024-003494","DOIUrl":"10.1136/svn-2024-003494","url":null,"abstract":"<p><strong>Background: </strong>Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke (AIS). Accumulative evidence suggests that mesenchymal stem cell (MSC) effectively ameliorates stroke outcomes. Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.</p><p><strong>Methods: </strong>Patients with AIS and healthy individuals were enrolled in the study. Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC (BM-MSC) right after reperfusion. Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin. Thickness of mucus was assessed with Alcian blue staining. Hepatic glucocorticoid (GC) metabolism was analysed with expression of HSD11B2, HSD11B1 and SRD5A1.</p><p><strong>Results: </strong>We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation. The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia. Transferred-BM-MSC restored the mucus thickness, thus preserving gut microbiota homeostasis and preventing enterobacterial invasion. Mechanistically, the transferred-BM-MSC stationed in the liver and enhanced peroxisome proliferator-activated receptor γ signalling in hepatocytes. Consequently, expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.</p><p><strong>Conclusions: </strong>Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut-brain axis in AIS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376180","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}
Angela C C Jochems, Susana Muñoz Maniega, Una Clancy, Carmen Arteaga Reyes, Daniela Jaime Garcia, Maria Del C Valdés Hernández, Francesca M Chappell, Gayle Barclay, Charlotte Jardine, Donna McIntyre, Iona Gerrish, Stewart Wiseman, Michael S Stringer, Michael J Thrippleton, Fergus Doubal, Joanna M Wardlaw
{"title":"Definitions of white matter hyperintensity change: impact on estimates of progression and regression.","authors":"Angela C C Jochems, Susana Muñoz Maniega, Una Clancy, Carmen Arteaga Reyes, Daniela Jaime Garcia, Maria Del C Valdés Hernández, Francesca M Chappell, Gayle Barclay, Charlotte Jardine, Donna McIntyre, Iona Gerrish, Stewart Wiseman, Michael S Stringer, Michael J Thrippleton, Fergus Doubal, Joanna M Wardlaw","doi":"10.1136/svn-2024-003300","DOIUrl":"https://doi.org/10.1136/svn-2024-003300","url":null,"abstract":"<p><strong>Background: </strong>White matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression.</p><p><strong>Methods: </strong>We recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1-3 months after stroke and 1 year later. We assessed WMH volume (in absolute mL and % intracranial volume) and applied four different definitions, including two thresholds (based on SD or mL), percentile and quintile approaches.</p><p><strong>Results: </strong>In 198 participants, mean age 65.5 (SD=11.13), baseline WMH volume was 15.46 mL (SD=19.2), the mean net WMH volume change was 0.98 mL (SD=2.84), range -7.98 to +12.84 mL. Proportion regressing/stable/progressing WMH were threshold 1 (SD), 29.8%/55.6%/14.6%; threshold 2(mL), 29.8%/16.7%/53.5%; percentile approach, 28.3%/21.2%/50.5%. The quintile approach includes five groups with quintile 3 reflecting no change (N=40), quintiles 1 and 2 any WMH decrease (N=80) and quintiles 4 and 5 any WMH increase (N=78).</p><p><strong>Conclusions: </strong>Different WMH change definitions cause big differences in how participants are categorised; additionally, non-normal WMH distribution precludes use of some definitions. Consistent use of an appropriate definition would facilitate data comparisons, particularly in clinical trials of potential WMH treatments.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367094","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}
Ubong Udoh, Rena Seeger, Brian Dewar, Emma Cummings, Sophia Gocan, Stuart Nicholls, Mark Fedyk, Victoria Shepherd, Jeff Perry, Robert Fahed, Tim Ramsay, Jamie Brehaut, Michael D Hill, Alexandre Y Poppe, Bijoy K Menon, Richard H Swartz, Dar Dowlatshahi, Michel Shamy
{"title":"Advance Consent for participation in Acute Stroke Trials (ACTION): protocol for a feasibility study.","authors":"Ubong Udoh, Rena Seeger, Brian Dewar, Emma Cummings, Sophia Gocan, Stuart Nicholls, Mark Fedyk, Victoria Shepherd, Jeff Perry, Robert Fahed, Tim Ramsay, Jamie Brehaut, Michael D Hill, Alexandre Y Poppe, Bijoy K Menon, Richard H Swartz, Dar Dowlatshahi, Michel Shamy","doi":"10.1136/svn-2023-003029","DOIUrl":"https://doi.org/10.1136/svn-2023-003029","url":null,"abstract":"<p><strong>Introduction: </strong>Obtaining informed consent for research from patients in medical emergencies remains a challenge, particularly in acute stroke care as treatment must be administered quickly and patients often arrive in the hospital in a state of incapacitation. Adaptations to standard consenting approaches-such as the use of surrogate consent or deferral of consent-have significant limitations. This feasibility study aims to test a new consenting approach in acute stroke care that we call advance consent. Advance consent has the potential to render emergency trial enrolment faster, fairer and more transparent, leading to more generalisable results.</p><p><strong>Methods and design: </strong>We will conduct a five-part study at The Ottawa Hospital, a quaternary care stroke centre: (1) administering questionnaires in the Ottawa Hospital Stroke Prevention Clinic that will examine patients' perspectives on research participation and advance consent; (2) inviting participants to consent in advance to any or both currently enrolling acute stroke trials; (3) tracking patient enrolment into these trials over 1 year; (4) administering a follow up questionnaire to participants at 1 year and (5) administering a questionnaire to participating hospital staff in order to interrogate their experiences with advance consent. Outcomes include but are not limited to eligibility rate, recruitment rate, withdrawal rate and the proportion of patients whose advance consent results in trial enrolment.</p><p><strong>Conclusion: </strong>This study will test the feasibility of enrolling patients at risk of stroke into acute stroke trials using advance consent.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367093","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}
Bin Sheng, Sen Gao, XiangXin Chen, Yang Liu, Niansheng Lai, Jin Dong, Jiaqing Sun, Yan Zhou, Lingyun Wu, Chun-Hua Hang, Wei Li
{"title":"Exosomes-mediated delivery of miR-486-3p alleviates neuroinflammation via SIRT2-mediated inhibition of mitophagy after subarachnoid hemorrhage.","authors":"Bin Sheng, Sen Gao, XiangXin Chen, Yang Liu, Niansheng Lai, Jin Dong, Jiaqing Sun, Yan Zhou, Lingyun Wu, Chun-Hua Hang, Wei Li","doi":"10.1136/svn-2024-003509","DOIUrl":"https://doi.org/10.1136/svn-2024-003509","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation participates in the pathogenesis of subarachnoid haemorrhage (SAH); however, no effective treatments exist. MicroRNAs regulate several aspects of neuronal dysfunction. In a previous study, we found that exosomal miR-486-3p is involved in the pathophysiology of SAH. Targeted delivery of miR-486-3p without blood-brain barrier (BBB) restriction to alleviate SAH is a promising neuroinflammation approach.</p><p><strong>Methods: </strong>In this study, we modified exosomes (Exo) to form an RVG-miR-486-3p-Exo (Exo/miR) to achieve targeted delivery of miR-486-3p to the brain. Neurological scores, brain water content, BBB damage, flow cytometry and FJC staining were used to determine the effect of miR-486-3p on SAH. Western blot analysis, ELISA and RT-qPCR were used to measure relevant protein and mRNA levels. Immunofluorescence staining and laser confocal detection were used to measure the expression of mitochondria, lysosomes and autophagosomes, and transmission electron microscopy was used to observe the level of mitophagy in the brain tissue of mice after SAH.</p><p><strong>Results: </strong>Tail vein injection of Exo/miR improved targeting of miR-486-3p to the brains of SAH mice. The injection reduced levels of neuroinflammation-related factors by changing the phenotype switching of microglia, inhibiting the expression of sirtuin 2 (SIRT2) and enhancing mitophagy. miR-486-3p treatment alleviated neurobehavioral disorders, brain oedema, BBB damage and neurodegeneration. Further research found that the mechanism was achieved by regulating the acetylation level of peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α) after SIRT2 enters the nucleus.</p><p><strong>Conclusion: </strong>Exo/miR treatment attenuates neuroinflammation after SAH by inhibiting SIRT2 expression and stimulating mitophagy, suggesting potential clinical applications.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367095","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":"Extracellular vesicles bearing serum amyloid A1 exacerbate neuroinflammation after intracerebral haemorrhage.","authors":"Huimin Zhu, Ningning Wang, Yingying Chang, Ying Zhang, Shihe Jiang, Xiaoping Ren, Meng Yuan, Haoxiao Chang, Wei-Na Jin","doi":"10.1136/svn-2024-003525","DOIUrl":"https://doi.org/10.1136/svn-2024-003525","url":null,"abstract":"<p><strong>Introduction: </strong>Intracerebral haemorrhage (ICH) elicits a robust inflammatory response, which significantly contributes to secondary brain damage. Extracellular vesicles (EVs) play a pivotal role in intercellular communication by transporting immune-regulatory proteins. However, the precise contribution of these EV-carried proteins to neuroinflammation following ICH remains elusive. Here, we identified proteins dysregulated in EVs and further studied the EVs-enriched Serum amyloid A 1 (SAA1) to understand its role in neuroinflammation and ICH injury.</p><p><strong>Methods: </strong>We used mass spectrometry to analyse the EV protein cargo isolated from plasma samples of 30 ICH patients and 30 healthy controls. To validate the function of the dysregulated protein SAA1, an ICH mouse model was conducted to assess the effects of SAA1 neutralisation on brain oedema, neurological function and infiltration of peripheral leucocytes.</p><p><strong>Results: </strong>49 upregulated proteins and 12 downregulated proteins were observed in EVs from ICH patients compared with controls. Notably, SAA1 demonstrated a significant increase in EVs associated with ICH. We observed that exogenous SAA1 stimulation led to an augmentation in the population of microglia and astrocytes, exacerbating neuroinflammation. Neutralising SAA1 with an anti-SAA1 monoclonal antibody (mAb) diminished the prevalence of proinflammatory microglia and the infiltration of peripheral leucocytes, which ameliorates brain oedema and neurological function in ICH mice.</p><p><strong>Conclusion: </strong>Our findings provide compelling evidence implicating EVs and their cargo proteins in ICH pathogenesis. SAA1 emerges as a potential therapeutic target for mitigating neuroinjury and neuroinflammation following ICH.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367096","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":"Angioplasty and/or stenting following successful mechanical thrombectomy for intracranial atherosclerosis-related emergent large vessel occlusive stroke (ASSET): protocol of a multicentre randomised trial.","authors":"Geng Liao, Hongyu Qiao, Chengbo Dai, Weiwen Yi, Liang Zhang, Zai Liang, Li Li, Yuemei He, Zhenyu Zhang, Zhong Ji, Li'an Huang","doi":"10.1136/svn-2024-003435","DOIUrl":"https://doi.org/10.1136/svn-2024-003435","url":null,"abstract":"<p><strong>Rationale: </strong>The management of residual stenosis after mechanical thrombectomy in patients with intracranial atherosclerotic stenosis-related emerge large vessel occlusive (ICAS-LVO) stroke is still unclear question in clinical practice.</p><p><strong>Aim: </strong>To demonstrate the design of a clinical trial on emergency balloon angioplasty and/or stenting (BAS) combined with standard medical treatment (SMT) for residual stenosis of ICAS-LVO stroke patients with successful recanalisation.</p><p><strong>Design: </strong>ASSET is a multicentre, prospective, randomised, open-label, blinded end-point, controlled clinical trial designed (PROBE) by investigators. This trial evaluates the effectiveness and the safety of emergency BAS in combination with SMT compared with SMT alone in ICAS-LVO stroke patients with successful recanalisation (defined as expanded treatment in cerebral ischaemia grade of 2b50-3 and maintained for more than 20 min) and residual stenosis (defined as ≥50%) up to 24 hours after the onset of symptoms or the last known well.</p><p><strong>Outcome: </strong>The primary outcome assessed at 90 (±7) days after randomisation is the incidence of ischaemic stroke in the responsible vessel. Symptomatic intracranial haemorrhage within 24 (±3) hours is the primary safety outcome.</p><p><strong>Discussion: </strong>The ASSET trial is designed to provide strong evidence on the effectiveness and safety of emergency BAS to treat residual stenosis after successful recanalisation in patients with ICAS-LVO stroke.</p><p><strong>Trial registration number: </strong>ChiCTR2300079069.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356519","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}
Xiqian Yuan, Siyuan Hu, Xiaochong Fan, Chao Jiang, Yan Xu, Ruochen Hao, Zili Xu, Yiyang Yu, Yousef Rastegar-Kashkooli, Leo Huang, Tom J Wang, Qiao Wang, Songxue Su, Limin Wang, Junyang Wang, Menglu Wang, Yun Tai Kim, Ujjal K Bhawal, Fushun Wang, Ting Zhao, Junmin Wang, Xuemei Chen, Jian Wang
{"title":"Central post-stroke pain: advances in clinical and preclinical research.","authors":"Xiqian Yuan, Siyuan Hu, Xiaochong Fan, Chao Jiang, Yan Xu, Ruochen Hao, Zili Xu, Yiyang Yu, Yousef Rastegar-Kashkooli, Leo Huang, Tom J Wang, Qiao Wang, Songxue Su, Limin Wang, Junyang Wang, Menglu Wang, Yun Tai Kim, Ujjal K Bhawal, Fushun Wang, Ting Zhao, Junmin Wang, Xuemei Chen, Jian Wang","doi":"10.1136/svn-2024-003418","DOIUrl":"https://doi.org/10.1136/svn-2024-003418","url":null,"abstract":"<p><p>Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356520","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}
Enayatullah Baki, Lea Baumgart, Victoria Kehl, Felix Hess, Andreas Wolfgang Wolff, Arthur Wagner, Moritz Roman Hernandez Petzsche, Tobias Boeckh-Behrens, Bernhard Hemmer, Bernhard Meyer, Jens Gempt, Silke Wunderlich
{"title":"Predictors of malignant swelling in space-occupying cerebellar infarction.","authors":"Enayatullah Baki, Lea Baumgart, Victoria Kehl, Felix Hess, Andreas Wolfgang Wolff, Arthur Wagner, Moritz Roman Hernandez Petzsche, Tobias Boeckh-Behrens, Bernhard Hemmer, Bernhard Meyer, Jens Gempt, Silke Wunderlich","doi":"10.1136/svn-2024-003360","DOIUrl":"10.1136/svn-2024-003360","url":null,"abstract":"<p><strong>Background: </strong>Malignant swelling is a fatal complication that can occur abruptly in space-occupying cerebellar infarction. We aimed to establish markers that predict malignant swelling in cerebellar infarction.</p><p><strong>Methods: </strong>We retrospectively analysed data of stroke patients who were treated in our hospital between 2014 and 2020. Malignant swelling was defined as a mass effect in the posterior cranial fossa, accompanied by a decrease in consciousness due to compression of the brainstem and/or the development of obstructive hydrocephalus. Statistical analyses were performed on multiple variables to identify predictors of malignant swelling.</p><p><strong>Results: </strong>Among 7284 stroke patients, we identified 487 patients with an infarct in the cerebellum. 93 patients were suitable for analysis having space-occupying cerebellar infarction. 33 of 93 (35.5%) patients developed malignant swelling. Multivariable analysis revealed infarct volume as the main predictor being independently associated with the development of malignant swelling with a cut-off infarct volume of 38 cm<sup>3</sup> being associated with a swelling rate of >50% (OR 32.0, p<0.001). Higher NIHSS (National Institutes of Health Stroke Scale) score on admission (median NIHSS 12 vs 4, OR 1.078; p=0.008) and the presence of additional brainstem infarction (51.5% vs 16.7%, OR 5.312; p=0.013) were associated with the development of malignant swelling in univariate analyses. 13 of 33 (39.4%) cases of malignant swellings occurred after more than 3 days.</p><p><strong>Conclusions: </strong>Infarct volume was the key significant predictor of malignant swelling in space-occupying cerebellar infarction. With many cases of malignant swelling occurring after more than 72 hours, we advocate prolonged neurological monitoring.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113761","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":"Why non-human primates are needed in stroke preclinical research.","authors":"Xiya Long, Jinsheng Zeng","doi":"10.1136/svn-2024-003504","DOIUrl":"https://doi.org/10.1136/svn-2024-003504","url":null,"abstract":"<p><p>Numerous seemingly promising cerebroprotectants previously validated in rodents almost all have failed in stroke clinical trials. The failure of clinical translation strikes an essential need to employ more ideal animal models in stroke research. Compared with the most commonly used rodent models of stroke, non-human primates (NHPs) are far more comparable to humans regarding brain anatomy, functionality and pathological features. The aim of this perspective was to summarise the advantages of NHPs stroke models over rodents, discuss the current limitations of NHPs models, and cast an outlook on the future development of NHPs in stroke preclinical research.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113762","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}
An Tian, Ziwei Cui, Jian Ren, Yeqing Ren, Ming Ye, Guilin Li, Chuan He, Xiaoyu Li, Gao Zeng, Peng Hu, Yongjie Ma, Jiaxing Yu, Jingwei Li, Lisong Bian, Fan Yang, Qianwen Li, Feng Ling, Tao Hong, Liyong Sun, Hongqi Zhang
{"title":"Surgical timing and long-term outcomes in patients with severe haemorrhagic spinal cord cavernous malformations.","authors":"An Tian, Ziwei Cui, Jian Ren, Yeqing Ren, Ming Ye, Guilin Li, Chuan He, Xiaoyu Li, Gao Zeng, Peng Hu, Yongjie Ma, Jiaxing Yu, Jingwei Li, Lisong Bian, Fan Yang, Qianwen Li, Feng Ling, Tao Hong, Liyong Sun, Hongqi Zhang","doi":"10.1136/svn-2023-002745","DOIUrl":"10.1136/svn-2023-002745","url":null,"abstract":"<p><strong>Background: </strong>Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations (SCCMs) to eliminate the occupation and associated subsequent lifelong haemorrhagic risk. However, the timing of surgical intervention remains controversial, especially for patients in the acute stage after severe haemorrhage.</p><p><strong>Methods: </strong>Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively reviewed. The Modified McCormick Scale (MMS) was used to evaluate neurological and disability status. All medical information was reviewed, and all patients were followed up for at least 6 months.</p><p><strong>Results: </strong>A total of 279 patients were ultimately included. With regard to long-term outcomes, 110 (39.4%) patients improved, 159 (57.0%) remained unchanged and 10 (3.6%) worsened. For patients with an MMS score of 2-5 on admission, in univariate and multivariate analyses, a ≤6 weeks period between onset and surgery (adjusted OR 3.211, 95% CI 1.504 to 6.856, p=0.003) was a significant predictor of improved MMS. Among 69 patients who first presented with severe haemorrhage, undergoing surgery within 6 weeks of the onset of severe haemorrhage (adjusted OR 4.901, 95% CI 1.126 to 21.325, p=0.034) was significantly associated with improvement of MMS score.</p><p><strong>Conclusion: </strong>Surgical timing can influence the long-term outcome of SCCMs. For patients with symptomatic SCCMs, especially those with severe haemorrhage, early surgical intervention within 6 weeks can provide more benefit.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"439-445"},"PeriodicalIF":2.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72211460","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
