Journal of Investigative Medicine最新文献

{"title":"Revascularisation patterns and characteristics after erythropoietin pretreatment and multiple burr holes in patients who had acute stroke with perfusion impairment.","authors":"Seong-Joon Lee, So Young Park, Geun Hwa Park, Jin Soo Lee, Yong Cheol Lim, Ji Man Hong","doi":"10.1136/svn-2023-002831","DOIUrl":"10.1136/svn-2023-002831","url":null,"abstract":"<p><strong>Background: </strong>Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals.</p><p><strong>Methods: </strong>We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups.</p><p><strong>Results: </strong>Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform.</p><p><strong>Conclusions: </strong>Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"95-103"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184756","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":"Paediatric intracranial dural arteriovenous fistulas: clinical characteristics, treatment outcomes and prognosis.","authors":"Xin Su, Yongjie Ma, Zihao Song, Ming Ye, Hongqi Zhang, Peng Zhang","doi":"10.1136/svn-2024-003122","DOIUrl":"10.1136/svn-2024-003122","url":null,"abstract":"<p><strong>Background: </strong>Compared with dural arteriovenous fistulas (DAVFs) in adult, paediatric DAVFs are notable for distinct clinical manifestations, low cure rate and poor prognosis. However, due to the limitations of small sample sizes, the long-term prognosis and follow-up data have not been described.</p><p><strong>Methods: </strong>Clinical data from 43 consecutive paediatric DAVFs were documented and analysed between 2002 and 2022 at the author's institution. They were divided into infantile (Lasjaunias classification) and non-infantile (adult type and dural sinus malformation (DSM)) type DAVFs based on prognosis differences.</p><p><strong>Results: </strong>Their mean age at first symptoms was 8.4±6.0 years. 29 boys and 14 girls presented between at birth and 18 years of age. 5 of 10 patients ≤1 year of age presented with asymptomatic cardiomegaly compared with 5/33 patients >1 year of age (p=0.022). 42 (88.4%) patients received endovascular treatment alone, while 9.3% underwent radiosurgery, burr hole embolisation or surgery. 28 (65.1%) patients experienced DAVF obliteration by the end of treatment. Among them, 26 cases underwent embolisation alone, one case had embolisation in conjunction with surgery, and one case underwent burr hole embolisation. The overall complication rate among patients was 9.3%, all resulting from endovascular treatment. According to the Lasjaunias Classification, there were 18 cases of adult type, 17 cases of infantile type and 8 cases of DSM. Compared with non-infantile-type DAVFs, infantile-type DAVFs showed more times of treatment, lower cure rate and worse prognosis (p<0.001, 0.003 and 0.021, respectively). The average follow-up duration was 41.4±36.2 months (3-228 months). 8 (22.9%) patients died.</p><p><strong>Conclusions: </strong>Most adult-type DAVFs and DSMs can now be effectively treated with embolisation, resulting in good outcomes and prognosis. However, there are still challenges in treating infantile-type DAVFs, and the prognosis is frequently poor.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"104-111"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262236","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":"Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.","authors":"Guangxiong Yuan, Jun Zhang, Zekang Ye, Jingping Sun, Xiaochuan Huo, Yuesong Pan, Mengxing Wang, Xiao Peng, Chanjuan Zheng, Xueyao Lei, Zhongrong Miao, Xueli Cai","doi":"10.1136/svn-2024-003120","DOIUrl":"10.1136/svn-2024-003120","url":null,"abstract":"<p><strong>Background and purpose: </strong>The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions.</p><p><strong>Methods: </strong>In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes.</p><p><strong>Results: </strong>122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54).</p><p><strong>Conclusions: </strong>Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"71-77"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081893","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 Ferrous iron on the prevention of Vascular cOgnitive impaiRment among patients with cerebral Infarction/TIA (FAVORITE): rationale and design of a multicentre randomised trial.","authors":"Qian Jia, Peng Lei, Li Sun, Wei Li Jia, Yuesong Pan, Baoshi Yuan, Yinkai Wang, Qi Zhou, Xia Meng, Jing Jing, Jinxi Lin, Anxin Wang, Shuting Zhang, Zhen Hong, Yu Yang, Yunyun Xiong, Zixiao Li, Yilong Wang, Xingquan Zhao, Yongjun Wang","doi":"10.1136/svn-2023-002644","DOIUrl":"10.1136/svn-2023-002644","url":null,"abstract":"<p><strong>Background: </strong>The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke. Anaemia or low haemoglobin was possibly associated with an increased risk of poststroke cognitive impairment. Whether supplement of ferrous iron to correct anaemia reduces the risk of VCI and improves adverse outcomes in patients with ischaemic cerebrovascular disease remains uncertain.</p><p><strong>Aim: </strong>We aim to introduce the design and rationale of the safety and efficacy of Ferrous iron on the prevention of Vascular cOgnitive impaiRment in patients with cerebral Infarction or TIA (FAVORITE) trial.</p><p><strong>Design: </strong>FAVORITE is a randomised, placebo-controlled, double-blind, multicentre trial that compares supplement of ferrous iron with placebo for recent minor stroke/TIA patients complicated with mild anaemia or iron deficiency: Ferrous succinate sustained-release tablet 0.2 g (corresponding to 70 mg of elemental iron) once daily after or during breakfast for 12 weeks or placebo with much the same colour, smell and size as ferrous iron once daily during or after breakfast for 12 weeks. All paticipants will be followed within the next year.</p><p><strong>Study outcomes: </strong>The primary effective outcome is the incidence of VCI at 3 months after randomisation and the primary safety outcome includes any gastrointestinal adverse event during 3 months.</p><p><strong>Discussion: </strong>The FAVORITE trial will clarify whether supplement of ferrous iron to correct low haemoglobin reduces the risk of VCI in patients with recent ischaemic stroke or TIA complicated with mild anaemia or iron deficiency compared with placebo.</p><p><strong>Trial registration number: </strong>NCT03891277.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"136-141"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094701","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":"Intensity of statin therapy after ischaemic stroke and long-term outcomes: a nationwide cohort study.","authors":"Ville Kytö, Julia Åivo, Jori O Ruuskanen","doi":"10.1136/svn-2024-003230","DOIUrl":"10.1136/svn-2024-003230","url":null,"abstract":"<p><strong>Background: </strong>Statins are essential for secondary prevention after ischaemic stroke (IS). However, statin intensity recommendations differ, and there is a concern about intracerebral haemorrhage (ICH). We studied the long-term impacts of initial statin intensity following IS.</p><p><strong>Methods: </strong>Consecutive patients using high-intensity, moderate-intensity or low-intensity statin early after IS (n=45 512) were retrospectively studied using national registries in Finland. Differences were adjusted using multivariable regression. The primary outcome was all-cause death within 12-year follow-up (median 5.9 years). Secondary outcomes were recurrent IS, cardiovascular death and ICH studied using competing risk analyses.</p><p><strong>Results: </strong>High-intensity therapy was initially used by 16.0%, moderate-intensity by 73.8% and low-intensity by 10.2%. Risk of death was lower with high-intensity versus moderate-intensity (adjusted HR (adj.HR) 0.92; 95% CI 0.87 to 0.97; number needed to treat (NNT) 32.0), with moderate-intensity versus low-intensity (adj.HR 0.91; 95% CI 0.87 to 0.95; NNT 27.5) and with high-intensity versus low-intensity (adj.HR 0.83; 95% CI 0.78 to 0.89; NNT 14.6) statin. There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS (p<0.0001) and cardiovascular death (p<0.0001). The occurrence of ICH was not associated with initial statin intensity (p=0.646).</p><p><strong>Conclusions: </strong>Following IS, more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH. These findings emphasise the importance of high statin intensity shortly after IS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"142-145"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321834","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 versus alteplase for acute ischaemic stroke in the elderly patients: a post hoc analysis of the TRACE-2 trial.","authors":"Yunyun Xiong, Liyuan Wang, Yuesong Pan, Mengxing Wang, Lee H Schwamm, Chunmiao Duan, Bruce C V Campbell, Shuya Li, Manjun Hao, Na Wu, Zhixin Cao, Shuangzhe Wu, Zixiao Li, Yongjun Wang","doi":"10.1136/svn-2023-003048","DOIUrl":"10.1136/svn-2023-003048","url":null,"abstract":"<p><strong>Background: </strong>The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke (AIS) is uncertain. We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged ≥80 years.</p><p><strong>Methods: </strong>We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial, a randomised, phase 3, non-inferiority clinical trial. Disabling AIS patients aged ≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Symptomatic intracranial haemorrhage (sICH) within 36 hours was the safety outcome.</p><p><strong>Results: </strong>Of 137 participants, mRS 0-1 at 90 days occurred in 37 (49.3%) of 75 in the tenecteplase group vs 20 (33.9%) of 59 in the alteplase group (risk ratio (RR) 1.47, 95% CI 0.96 to 2.23). sICH within 36 hours was observed in 3 (4.0%) of 76 in the tenecteplase group and two (3.3%) of 61 in the alteplase group (RR 1.30, 95% CI 0.20 to 8.41).</p><p><strong>Conclusions: </strong>The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients, which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"112-119"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301897","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":"Racial disparities in access to, and outcomes of, acute ischaemic stroke treatments in the USA.","authors":"Luke Kiefer, David Daniel, Sai Polineni, Mandip Dhamoon","doi":"10.1136/svn-2023-003051","DOIUrl":"10.1136/svn-2023-003051","url":null,"abstract":"<p><strong>Background: </strong>Racism contributes to higher comorbid risk factors and barriers to preventive measures for black Americans. Advancements in systems of care, tissue plasminogen activator (tPA) availability and endovascular thrombectomy (ET) have impacted practice and outcomes while outpacing contemporary investigation into acute ischaemic stroke (AIS) care disparities. We examined whether recent data suggest ongoing disparity in AIS interventions and outcomes, and if hospital characteristics affect disparities.</p><p><strong>Methods: </strong>We examined 2016-2019 fee-for-service Medicare inpatient data. We ran unadjusted logistic regression models to calculate ORs and 95% CI for two interventions (tPA and ET) and four outcomes (inpatient mortality, 30-day mortality, discharge home and outpatient visit within 30 days), with the main predictor black versus white race, additionally adjusting for demographics, hospital characteristics, stroke severity and comorbidities.</p><p><strong>Results: </strong>805 181 AIS admissions were analysed (12.4% black, 87.6% white). Compared with white patients, black patients had reduced odds of receiving tPA (OR 0.71, 95% CI 0.69 to 0.74, p<0.0001) and ET (0.69, 95% CI 0.65 to 0.72, p<0.0001). After tPA, black patients had reduced odds of 30-day mortality (0.77, 95% CI 0.72 to 0.82, p<0.0001), discharge home (0.72, 95% CI 0.68 to 0.77, p<0.0001) and outpatient visit within 30 days (0.89, 95% CI 0.84 to 0.95, p=0.0002). After ET, black patients had reduced odds of 30-day mortality (0.71, 95% CI 0.63 to 0.79, p<0.0001) and discharge home (0.75, 95% CI 0.64 to 0.88, p=0.0005). Adjusted models showed little difference in the magnitude, direction or significance of the main effects.</p><p><strong>Conclusions: </strong>Black patients were less likely to receive AIS treatments, and if treated had lower likelihood of 30-day mortality, discharge home and outpatient visits. Despite advancements in practice and therapies, racial disparities remain in the modern era of AIS care and are consistent with inequalities previously identified over the last 20 years. The impact of hospital attributes on AIS care disparities warrants further investigation.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"65-70"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081899","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":"Left atrial appendage closure for patients with atrial fibrillation at high intracranial haemorrhagic risk.","authors":"Avia Abramovitz Fouks, Shadi Yaghi, Elif Gokcal, Alvin S Das, Ofer Rotschild, Scott B Silverman, Aneesh B Singhal, Jorge Romero, Sunil Kapur, Steven M Greenberg, Mahmut Edip Gurol","doi":"10.1136/svn-2024-003142","DOIUrl":"10.1136/svn-2024-003142","url":null,"abstract":"<p><strong>Background and objectives: </strong>Although left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed the detailed neurological indications for LAAC and outcomes after LAAC in high ICH risk patients.</p><p><strong>Methods: </strong>Study population included consecutive patients with NVAF who underwent LAAC in a single hospital network between January 2015 and October 2021 because of prior ICH or the presence of high ICH risk imaging markers on brain MRI (cerebral microbleeds (CMBs)). Primary safety and efficacy outcome measures were the occurrence of ICH and thromboembolic events, respectively, after LAAC.</p><p><strong>Results: </strong>Among 146 patients with NVAF who underwent LAAC for high ICH risk, 122 had a history of ICH, while 24 presented with high ICH risk imaging markers only. Mean age was 75.7±7.61, 42 (28.8%) were women. Mean CHA₂DS₂-VASc score was 5.23±1.52. Of 122 patients with ICH history, 58 (47.5%) had intraparenchymal haemorrhage (IPH), 40 (32.8%) had traumatic ICH (T-ICH) and 18 (14.7%) had non-traumatic subdural haemorrhage. Of 85 patients with brain MRIs including necessary sequences, 43 (50.6%) were related to cerebral amyloid angiopathy and 37 (43.5%) to hypertensive microangiopathy. While 70% of patients were discharged on oral anticoagulants (OAC), 92% were not taking OAC at 1 year. Over 2.12 years mean follow-up, one patient had recurrent non-traumatic IPH (incidence rate (IR) 0.32 per 100 patient-years), five had T-ICH (IR 1.61 per 100 patient-years) and six had an ischaemic stroke (IR 1.94 per 100 patient-years).</p><p><strong>Conclusions: </strong>Among patients with NVAF at high ICH risk, LAAC demonstrated a low risk of recurrent ICH or ischaemic stroke compared with previously published data. LAAC in high ICH risk populations should be considered in clinical practice per FDA approval and recent guidelines.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"86-94"},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184712","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":"Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation.","authors":"Cuiying Liu, Jiayi Guo, Longfei Guan, Junfa Li, Baohui Xu, Heng Zhao","doi":"10.1136/svn-2024-003442","DOIUrl":"https://doi.org/10.1136/svn-2024-003442","url":null,"abstract":"<p><strong>Background: </strong>Melatonin protects against ischaemic stroke in diabetic animal models, though the mechanisms involving brain and peripheral immune responses remain underexplored. We aimed to clarify how melatonin interacts with these immune responses to protect against stroke in diabetic mice.</p><p><strong>Methods: </strong>Type 1 diabetes mellitus (T1DM) was induced in mice using streptozotocin. RNA sequencing of brain tissue and peripheral blood mononuclear cells (PBMCs) was performed 24 hours poststroke. Inflammatory responses were evaluated 72 hours after ischaemia/reperfusion.</p><p><strong>Results: </strong>Melatonin reduced infarction and improved neurological function in T1DM mice. In the ischaemic brain, melatonin downregulated inflammatory factor expression, with bioinformatics identifying 62 differentially expressed genes (DEGs) related to inflammation and 11 associated with inflammasomes. Western blotting confirmed reductions in NLRP3, HMGB1 and Cleaved Caspase-1 expression. Flow cytometry showed reduced infiltration of CD8+T cells and neutrophils. Melatonin decreased IL-6, IL-1β and IL-4 levels. In PBMCs, RNA sequencing revealed 939 DEGs following melatonin treatment. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that downregulated DEGs were involved in metabolic pathways, and upregulated DEGs were enriched in the Jak-STAT signalling pathway. GO analysis showed that downregulated DEGs were enriched in the cytosol, and upregulated DEGs related to macromolecule modification. Protein-protein interaction analysis revealed that melatonin affected 38 inflammation-associated genes linked to key cytokines (Il6, Il1b, Ifng, Il4). Flow cytometry indicated melatonin increased CD8+T cells, monocytes and neutrophils in the blood, suggesting a reversal of immunosuppression. Multiplex cytokine assays showed melatonin decreased IL-6 and IFN-γ levels.</p><p><strong>Conclusion: </strong>Poststroke melatonin therapy reduces ischaemic brain damage in T1DM mice by modulating central and peripheral inflammatory responses.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505186","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":"Updates on vascular dementia.","authors":"Sabrina Ng, Ava Hornblass, Parnian Habibi, Salman Ikramuddin, Jeffrey Chen, Wayne Feng, Dongming Cai","doi":"10.1136/svn-2025-004048","DOIUrl":"https://doi.org/10.1136/svn-2025-004048","url":null,"abstract":"<p><p>Vascular dementia (VaD) is the second leading cause of dementia after Alzheimer's disease (AD). In comparison to AD, there is a decline in the incidence of VaD due to recent improvements in cardiovascular risk factors. Brain hypoperfusion and hypoxia due to vascular pathologies have been postulated as the primary disease mechanism of VaD. However, other factors such as neuroinflammation may also contribute to the development of VaD. Non-modifiable and modifiable risk factors have been attributed to VaD. The clinical features overlapping between AD and VaD create significant challenges for physicians. Newly developed biomarkers may potentially help differentiate VaD from other forms of dementia. Unlike AD, there is no Food and Drug Administration-approved drug or device for treating VaD. Current treatment options mainly target symptoms rather than slowing the development or progression of VaD. There are ongoing research studies testing the efficacy of various therapeutic strategies for VaD. In this narrative review, we will summarise current findings on epidemiology, attributed risk factors and disease mechanisms, as well as emphasise the importance of optimising lifestyle modifications and comorbid condition management in preventing or slowing down the development of VaD. Finally, current therapies and ongoing research studies of novel therapeutic interventions such as stem-cell therapy and neuromodulation are highlighted.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505192","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}