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Background: Despite high recanalization rates of > 90% after endovascular thrombectomy (EVT) clinical outcome in around 50% of treated acute ischemic stroke (AIS) patients is still poor. Novel treatments augmenting the beneficial effects of recanalization are eagerly awaited, but this requires mechanistic insights to explain and overcome futile recanalization. Main body: At least two mechanisms contribute to futile recanalization after cerebral large vessel occlusions (LVO): (i) the no reflow phenomenon as evidenced by randomly distributed areas without return of blood flow despite reperfusion of large cerebral arteries, and (ii) ischemia/reperfusion (I/R) injury, the paradoxically harmful aspect of blood flow return in transiently ischemic organs. There is accumulating evidence from experimental stroke models that platelets and leukocytes interact and partly obstruct the microvasculature under LVO, and that platelet-driven inflammation (designated thrombo-inflammation) extends into the reperfusion phase and causes I/R injury. Blocking of platelet glycoprotein receptors (GP) Ib and GPVI ameliorated inflammation and I/R injury providing novel therapeutic options. Recently, MRI studies confirmed a significant, up to 40% infarct expansion after recanalization in AIS thereby proofing the existance of I/R injury in the human brain. Moreover, analysis of minute samples of ischemic arterial blood aspirated directly from the pial cerebral collateral circulation under LVO during the routine EVT procedure confirmed platelet activation and platelet-driven leukocyte accumulation in AIS and, thus, the principal transferability of pathophysiological stroke mechanisms from rodents to man. Two recently published clinical phase 1b/2a trials targeted (thrombo-) inflammation in AIS: The ACTIMIS trial targeting platelet GPVI by glenzocimab provided encouraging safety signals in AIS similar to the ApTOLL trial targeting toll-like receptor 4, a central receptor guiding stroke-induced innate immunity. However, both studies were not powered to show clinical efficacy. Conclusions: The fact that the significance of I/R injury in AIS has recently been formally established and given the decisive role of platelet-leukocytes interactions herein, new avenues for adjunct stroke treatments emerge. Adjusted study designs to increase the probability of success are of outmost importance and we look forward from what can be learned from the so far unpublished, presumbably negative ACTISAFE and MOST trials. [ABSTRACT FROM AUTHOR]

Background: A raised stress hyperglycaemia ratio (SHR) has been associated with all-cause mortality and may better discriminate than an absolute glucose value. The aim of this meta analysis and systematic review is to synthesise the evidence assessing the relationship between the SHR and all-cause mortality across three common cardiovascular presentations. Methods: We undertook a comprehensive search of Medline, Embase, Cochrane CENTRAL and Web of Science from the date of inception to 1st March 2024, and selected articles meeting the following criteria: studies of patients hospitalised for acute myocardial infarction, ischaemic stroke or acute heart failure reporting the risk (odds ratio or hazard ratio) for all-cause mortality associated with the SHR. A random effects model was used for primary analysis. Subgroup analysis by diabetes status and of mortality in the short and long term was undertaken. Risk of bias assessment was performed using the Newcastle Ottawa quality assessment scale. Results: A total of 32 studies were included: 26 studies provided 31 estimates for the meta-analysis. The total study population in the meta analysis was 80,010. Six further studies were included in the systematic review. Participants admitted to hospital with cardiovascular disease and an SHR in the highest category had a significantly higher risk ratio of all-cause mortality in both the short and longer term compared with those with a lower SHR (RR = 1.67 [95% CI 1.46–1.91], p < 0.001). This finding was driven by studies in the myocardial infarction (RR = 1.75 [95% CI 1.52–2.01]), and ischaemic stroke cohorts (RR = 1.78 [95% CI 1.26–2.50]). The relationship was present amongst those with and without diabetes (diabetes: RR 1.49 [95% CI 1.14–1.94], p < 0.001, no diabetes: RR 1.85 [95% CI 1.49–2.30], p < 0.001) with p = 0.21 for subgroup differences, and amongst studies that reported mortality as a single outcome (RR of 1.51 ([95% CI 1.29–1.77]; p < 0.001) and those that reported mortality as part of a composite outcome (RR 2.02 [95% CI 1.58–2.59]; p < 0.001). On subgroup analysis by length of follow up, higher SHR values were associated with increased risk of mortality at 90 day, 1 year and > 1year follow up, with risk ratios of 1.84 ([95% CI 1.32–2.56], p < 0.001), 1.69 ([95% CI 1.32–2.16], p < 0.001) and 1.58 ([95% CI 1.34–1.86], p < 0.001) respectively. Conclusions: A raised SHR is associated with an increased risk of all-cause mortality following myocardial infarction and ischaemic stroke. Further work is required to define reference values for the SHR, and to investigate the potential effects of relative hypoglycaemia. Interventional trials targeting to the SHR rather than the absolute glucose value should be undertaken. PROSPERO database registration: CRD 42023456421 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023456421 [ABSTRACT FROM AUTHOR]

Background: Atrial natriuretic peptide (ANP) has been associated with ischemic stroke (IS), but the underlying molecular mechanisms are not clear. The objective of this study was to examine whether DNA methylation and hydroxymethylation in the coding gene of ANP (NPPA) were associated with IS, as well as its functional outcome. Methods and results: DNA methylation and hydroxymethylation in NPPA promoter region were quantified by targeted bisulfite sequencing and APOBEC-coupled epigenetic sequencing, respectively, in 615 IS patients and 610 age- and sex-matched healthy controls. True methylation was calculated as the quantified methylation level minus the quantified hydroxymethylation level. The functional outcome of IS was evaluated by the modified Rankin Scale (mRS) at a 3-month follow-up visit after onset. Multiple testing was controlled by the false discovery rate approach. Of the nine CpG sites assayed, hypomethylation at eight CpGs was not only associated with an increased risk of having IS but also predicted a higher mRS score after onset (all q < 0.05) and hydroxymethylation at one CpG located at Chr1:11908348 was positively associated with IS (OR = 1.39, 95%CI:1.15–1.68, q < 0.05), after adjusting for covariates and multiple testing. While, hydroxymethylation levels at none of the CpGs assayed were significantly associated with the mRS score. Conclusions: DNA methylation and hydroxymethylation in NPPA promoter were associated with the risk of IS and its functional outcome in Chinese adults. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Methods: We used an established striatal whole-blood injection mouse model to mimic intracerebral hemorrhage-related secondary brain injury. Based on the spatiotemporal dynamics in our model, we calculated the necessary sample size (n = 24) and determined the most sensitive time point to detect potential group differences (48 h) prior to the experiments. The experimental setup, tissue processing and image analysis adhered to our published protocol. We randomized mice into three groups: C1-inhibitor treatment, placebo, and sham. Histology was standardized by taking eight anatomically predefined slices across the entire lesion. Lesion size, vascular leakage, and inflammatory responses were assessed using automated thresholding and dextran/ICAM1/CD45 intensity mapping. Investigators were blinded to group allocation during the experiment, tissue processing, and image analysis. Results: Whole blood injection resulted in significantly larger lesion size and more pronounced vascular leakage and cellular inflammation compared to the sham group. However, there was no difference in lesion size or inflammatory markers between the C1-inhibitor and placebo groups. In addition, there was no difference in the inflammatory response of the choroid plexus, which has been identified as a central organ orchestrating inflammation after intracerebral hemorrhage. Conclusion: The protective effect of C1-inhibitor might be isolated to pathophysiological processes with a predominant thromboinflammatory component, as in ischemia-reperfusion, but less so in permanent ischemia or intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome after acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on the quality of life in patients with AIS in China. Methods: This is a post hoc analysis of Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial. The quality of life was measured using the EuroQoL questionnaire, including EQ-5D and EQ visual analogue scale (EQ-VAS). The primary outcomes were changes in EQ-5D and EQ-VAS from baseline to day 14 and day 90 after randomization. Results: A total of 3219 patients with completed data on outcomes were enrolled, with median age of 63 years (interquartile range, 55–70) and 2,067 (64.2%) men. GDLM was associated with a significant decrease in scores of ED-5Q components (from 0 [no problem] to 3[extreme problem]), the mean difference between GDLM and placebo group was -0.14 for mobility, -0.11 for usual activities and self-care, -0.09 for pain/discomfort, and -0.34 for anxiety/depression on day 14, respectively. Similar results were observed on day 90. Additionally, there was statistically significant difference of changes in EQ-VAS between the GDLM group and the placebo group from baseline to day 14 (mean difference, 1.70; 95% confidence interval [CI], 0.78–2.62; P = 0.0003) and to day 90 after randomization (mean difference, 3.29; 95% CI, 2.37–4.22; P < 0.001). Conclusions: In this analysis of Chinese patients with AIS, GDLM could improve the 14-day and 90-day quality of life compared with the placebo. Trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02526225. Registration Date: 2016–02-01. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is a commonly seen cerebrovascular disease which seriously endangers the health of middle age and old people. However, its etiology and pathogenesis have not yet fully comprehended. miR-30 gene is a novel gene which may be involved in IS. However, no studies have investigated the relationship between IS and the single-nucleotide polymorphisms (SNPs) of miR-30. Therefore, this study examined the relationship between miR-30 polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) and the risk of IS. Methods: Totally 248 IS patients and 230 age-, sex- and race-matched controls were involved in this study. Based on SNPscan technique, four polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) were genotyped. Results: There exists a significant association between rs2222722 polymorphism and the risk of IS according to analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 1.616, 95% CI: 0.943–2.768, P = 0. 081); (AA vs. GG: adjusted OR = 2.447, 95% CI: 1.233–4.858, P = 0.011); dominant model: adjusted (OR = 1.806, 95% CI, 1.082–3.016, P = 0.024); (G vs. A: adjusted OR = 1.492, 95% CI: 1.148–1.939, P = 0.003). Besides, miR-30a expression was significantly higher in patients undergoing IS relative to that in controls (P < 0.05). Conclusions: To conclude, the rs2222722 polymorphism of the miR-30 gene shows a significant relationship to elevate the risk of IS in Chinese population. [ABSTRACT FROM AUTHOR]

Background: Intracranial atherosclerotic disease (ICAD) represents a leading cause of ischemic stroke worldwide, conferring increased risk of recurrent stroke and poor clinical outcomes among stroke survivors. Emerging evidence indicates a paradigm shift, pointing towards increasing detection rates of ICAD among White populations and an evolving epidemiological profile across racial and ethnic groups. The present review aims to provide a comprehensive overview of ICAD, focusing on its pathophysiology, diagnostic approach, and evolving epidemiological trends, including underlying mechanisms, advanced neuroimaging techniques for diagnostic evaluation, racial disparities in prevalence, and current and emerging management strategies. Main body: Atherosclerotic plaque accumulation and progressive arterial stenosis of major intracranial arteries comprise the pathophysiological hallmark of ICAD. In clinical practice, the diagnosis of intracranial artery stenosis (ICAS) or high-grade ICAS is reached when luminal narrowing exceeds 50% and 70%, respectively. Advanced neuroimaging, including high-resolution vessel wall MRI (HRVW-MRI), has recently enabled ICAD detection before luminal stenosis occurs. While earlier studies disclosed significant racial disparities in ICAS prevalence, with higher rates among Asians, Hispanics, and Blacks, recent evidence reveals rising detection rates of ICAD among White populations. Genetic, environmental and epigenetic factors have been suggested to confer an increased susceptibility of certain ethnicities and races to ICAD. Nevertheless, with improved accessibility to advanced neuroimaging, ICAD is increasingly recognized as an underlying stroke etiology among White patients presenting with acute ischemic stroke and stroke of undetermined etiology. While conventional management of ICAS entails risk factor modification, pharmacotherapy, and endovascular treatment in selected high-risk patients, substantial progress remains to be made in the management of ICAD at its early, pre-stenotic stages. Conclusion: ICAD remains a critical yet underappreciated risk factor for ischemic stroke across all populations, highlighting the need for increased awareness and improved diagnostic strategies. The emerging epidemiological profile of ICAD across racial groups necessitates a reassessment of risk factors, screening protocols and preventive strategies. Future research should focus on refining the diagnostic criteria and expanding the therapeutic options to cover the full spectrum of ICAD, with the aim of improving patient outcomes and reducing the global burden of intracranial atherosclerosis and stroke. [ABSTRACT FROM AUTHOR]

Background and objectives: This study aimed to employ machine learning techniques to predict the clinical efficacy of acupuncture as an intervention for patients with upper limb motor dysfunction following ischemic stroke, as well as to assess its potential utility in clinical practice. Methods: Medical records and digital subtraction angiography (DSA) imaging data were collected from 735 ischemic stroke patients with upper limb motor dysfunction who were treated with standardized acupuncture at two hospitals. Following the initial screening, 314 patient datasets that met the inclusion criteria were selected. We applied three deep-learning algorithms (YOLOX, FasterRCNN, and TOOD) to develop the object detection model. Object detection results pertaining to the cerebral vessels were integrated into a clinical efficacy prediction model (random forest). This model aimed to classify patient responses to acupuncture treatment. Finally, the accuracies and discriminative capabilities of the prediction models were assessed. Results: The object detection model achieved an optimal recognition rate, The mean average precisions of YOLOX, TOOD, and FasterRCNN were 0.61, 0.7, and 0.68, respectively. The prediction accuracy of the clinical efficacy model reached 93.6%, with all three-treatment response classification area under the curves (AUCs) exceeding 0.95. Feature extraction using the prediction model highlighted the significant influence of various cerebral vascular stenosis sites within the internal carotid artery (ICA) on prediction outcomes. Specifically, the initial and C1 segments of the ICA had the highest predictive weights among all stenosis sites. Additionally, stenosis of the middle cerebral, anterior cerebral, and posterior cerebral arteries exerted a notable influence on the predictions. In contrast, the stenosis sites within the vertebral artery exhibited minimal impact on the model's predictive abilities. Conclusions: Results underscore the substantial predictive influence of each cerebral vascular stenosis site within the ICA, with the initial and C1 segments being pivotal predictors. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS). Methods: Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-휿B pathway related protein, and vascular density markers were determined. Results: There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-휿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats. Conclusions: Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS. [ABSTRACT FROM AUTHOR]

Backgrounds: High-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI. Method: Data was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM). Results: A total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02). Conclusion: In patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI. Cumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

Background: Multivessel disease(MVD) is linked to a poorer prognosis, increased complications, longer hospital stays, and higher in-hospital mortality when compared to single-vessel disease(SVD).The purpose of this study is to explore the clinically relevant predictors of acute cornary syndrome (ACS) combined with MVD. Methods: This multicenter retrospective study included 68,378 ACS patients from 240 hospitals.The clinical data were retrospectively analyzed with univariate and multivariate analyses to identify the predictive factors for MVD. Results: When compared to SVD group, the MVD group showed a higher incidence of Major Adverse Cardiovascular Events(MACCEs), including all-cause death, myocardial infarction, stent thrombosis, and ischemic stroke during hospitalization, These differences were found to be statistically significant (P < 0.05).The multivariate analysis revealed that age over 75 years (OR: 1.246, 95% CI: 1.176, 1.319), LDL/HDL ratio > 1.98 (OR: 1.245, 95% CI: 1.192, 1.302), history of heart failure (OR: 1.446, 95% CI: 1.143, 1.829), hypertension (OR: 1.274, 95% CI: 1.225, 1.325), diabetes (OR: 1.341, 95% CI: 1.278, 1.406), eGFRs < 60 ml/min·1.73m2 (OR: 1.179, 95% CI: 1.112, 1.249), family history of CAD (OR: 1.236, 95% CI: 1.108, 1.379), and high homocysteine levels (OR: 1.209, 95% CI: 1.029, 1.420) are independent predictors of MVD. The incidence of multivessel disease increased from 37.7 to 58.6% with an increase in the number of predictive factors, while the incidence of single vessel disease decreased from 62.3 to 41.4%. This trend was statistically significant (P trend < 0.001). Conclusions: MVD is strongly correlated with a range of risk factors including diabetes, hypertension, LDL/HDL ratio greater than 1.98, hyperhomocysteinemia, family history of CAD, reduced glomerular filtration rate (< 60 ml/(min·1.73m2), age over 75 years, and a history of heart failure. Furthermore, as the number of predictive factors increases, the odds ratio (OR) for patients with MVD also increases, reaching 2.344 times the OR for patients without any predictive factors. [ABSTRACT FROM AUTHOR]

Background: High levels of low-density lipoprotein cholesterol (LDL-C) can lead to the occurrence and development of atherosclerosis, which is one of the important risk factors for ischemic stroke (IS). However, details regarding the evolution of the IS burden attributable to high LDL-C in China has not been available. The objective of this study was to examine the changes over time, from 1990 to 2019, in the burden of IS attributed to high levels of LDL-C in China and to estimate the individual impacts of age, period, and cohort on the burden of IS associated with high LDL-C. Methods: Detailed data on IS burden attributable to high LDL-C from 1990 to 2019 in China were extracted from the Global Burden of Disease (GBD) Study 2019. The numbers and age-standardized rates of IS-related mortality and disability-adjusted life years (DALYs) attributable to high LDL-C were assessed by age and sex. The annual percentage change (APC) and average annual percentage change (AAPC) in the burden of IS due to high LDL-C were analyzed using Joinpoint regression model. The age-period-cohort analysis was carried out to assess the individual impacts of age, period, and cohort on the trends over time of mortality and DALY rate. Results: The number of IS-related deaths and DALYs due to high LDL-C in China were 182.7 thousand and 4.43 million in 2019, respectively, both more than double the corresponding numbers reported in 1990. However, despite these increased, the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) remained unchanged. In 2019, men under 84 years of age had higher death and under 79 years of age had higher DALYs than women. However, above these ages, the gender disparities were reversed. Furthermore, age-specific rates of death, as well as DALY of IS attributable to high LDL-C in 2019 increased with age for both women and men, except for death in adults over 95 years old; and were greater in men than in women. From 1990 to 2019, males consistently had a higher ASMR and ASDR than females in China. During 1990–2019, the ASMR in women slightly decreased before 1997, sharply increased from 1997 to 2004, and then continuously decreased from 2004 to 2019, with an overall AAPC value of -0.4% (95% CI -0.8%, -0.0%). However, for the ASMR of men in China, the overall trend is upward and the AAPC is 0.5%(95% CI 0.1%, 0.8%). The ASDR in women and men had the similar trend as the ASMR over the time, with an AAPC of -0.4% (95% CI -0.7%, -0.1%) and 0.3% (95% CI 0.1%, 0.5%), respectively. The age-period-cohort analysis indicated a rise in period effects and a decline in cohort effects on mortality and DALY rate associated with IS caused by high LDL-C in both genders. Age effect on mortality rates from IS due to high LDL-C showed an exponential increased with age in all women and men except for the 60–69 age group and over 95 age group. The age relative risk of IS DALY rate due to high LDL-C increased with age in both genders except for 65–74 age group and over 95 age group. Conclusions: From 1990 to 2019, the burden of IS caused by high LDL-C in China significantly increased among both sexes combined and among men, while significantly decreased among women. Elderly have a substantial burden of IS attributable to high LDL-C. Therefore, effective and tailored strategies based on gender and age for IS primary prevention and management of IS and high LDL-C are urgently needed in China. [ABSTRACT FROM AUTHOR]

Background: An estimated 30% of patients with epilepsy experience drug-resistant epilepsy, which is the failure to control seizures despite the use of two or more antiseizure medications. Although other treatment options are considered, these alternatives often prove ineffective. Case presentation: A 60-year-old East Asian male patient diagnosed with drug-resistant epilepsy experienced several seizures daily despite being on eight different antiseizure medications. Seizures began at age 15. He underwent epilepsy surgery at age 34, yet the seizures persisted. An electroencephalogram revealed multifocal sharp waves in the left hemisphere. Cerebral hemorrhages at ages 47, 50, and 56 were caused by head trauma during seizures. The patient became wheelchair-bound and now resides in a nursing home. At age 58, after suffering an acute cerebral infarction due to occlusion of the left internal carotid artery, his daily seizures ceased entirely. Despite remaining wheelchair-bound, he did not experience a significant decline in his quality of life. The cessation of seizures has reduced his risk of further trauma, and he has remained seizure-free for 3 years on just one antiseizure medication. Conclusion: Surgical treatments for epilepsy often fail, with insufficient resection being a leading cause of these failures. In some cases, extensive destruction from an ischemic stroke may be beneficial. Furthermore, this case suggests that infarction therapy could be a potential treatment for patients with drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

Objective: The associations between the ratio of blood high-sensitivity C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) (hs-CRP/HDL-C ratio) and outcomes in patients with acute ischemic stroke (AIS) have yet to be established. This study is the first to examine the relationship between the hs-CRP/HDL-C ratio and three-month unfavorable outcomes in patients with AIS. Methods: This secondary analysis utilized data from a prospective cohort study involving 1559 AIS patients recruited at a South Korean hospital between January 2010 and December 2016. We constructed a binary logistic regression model to explore the association between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. An attempt was made to use a generalized additive model (GAM) with smooth curve fitting to elucidate potential nonlinear interactions. Furthermore, inflection points were identified via a recursive method, and binary logistic regression models were developed for each side of these inflection points. Ultimately, a log-likelihood ratio test was used to identify the most appropriate model for explaining the connection between the hs-CRP/HDL-C ratio and unfavorable outcomes in patients with AIS. Results: The incidence of unfavorable outcomes was 24.5%, with a median hs-CRP/HDL-C ratio of 3.64. After accounting for other factors, the binary logistic regression model revealed a statistically significant positive association between the hs-CRP/HDL-C ratio and the likelihood of poor outcomes in AIS patients (OR = 1.013, 95% CI: 1.005–1.022; P = 0.002). A nonlinear relationship was observed, with the first inflection point of the hs-CRP/HDL-C ratio at 42.74. Each 1-unit increase in the hs-CRP/HDL-C ratio was associated with a 2.4% greater risk of unfavorable outcomes (OR = 1.024, 95% CI: 1.011–1.038, P < 0.001). Conclusion: This study provides evidence of a positive and nonlinear correlation between the hs-CRP/HDL-C ratio and poor three-month functional outcomes in AIS patients. When the hs-CRP/HDL-C ratio was less than 42.74, a positive association was observed with the risk of unfavorable outcomes. This finding offers a reference for optimizing early individualized therapy and aids in clinical counseling for patients with AIS. [ABSTRACT FROM AUTHOR]

Background: Accurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers' anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect. Methods: A search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications' details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting. Results: Among the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38). Conclusions: Registered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs. [ABSTRACT FROM AUTHOR]

Background: Brain microglia and infiltrating monocyte-derived macrophages are vital in preserving blood vessel integrity after stroke. Understanding mechanisms that induce immune cells to adopt vascular-protective phenotypes may hasten the development of stroke treatments. IL-33 is a potent chemokine released from damaged cells, such as CNS glia after stroke. The activation of IL-33/ST2 signaling has been shown to promote neuronal viability and white matter integrity after ischemic stroke. The impact of IL-33/ST2 on blood-brain barrier (BBB) integrity, however, remains unknown. The current study fills this gap and reveals a critical role of IL-33/ST2 signaling in macrophage-mediated BBB protection after stroke. Methods: Transient middle cerebral artery occlusion (tMCAO) was performed to induce ischemic stroke in wildtype (WT) versus ST2 knockout (KO) male mice. IL-33 was applied intranasally to tMCAO mice with or without dietary PLX5622 to deplete microglia/macrophages. ST2 KO versus WT bone marrow or macrophage cell transplantations were used to test the involvement of ST2+ macrophages in BBB integrity. Macrophages were cocultured in transwells with brain endothelial cells (ECs) after oxygen-glucose deprivation (OGD) to test potential direct effects of IL33-treated macrophages on the BBB in vitro. Results: The ST2 receptor was expressed in brain ECs, microglia, and infiltrating macrophages. Global KO of ST2 led to more IgG extravasation and loss of ZO-1 in cerebral microvessels 3 days post-tMCAO. Intranasal IL-33 administration reduced BBB leakage and infarct severity in microglia/macrophage competent mice, but not in microglia/macrophage depleted mice. Worse BBB injury was observed after tMCAO in chimeric WT mice reconstituted with ST2 KO bone marrow, and in WT mice whose monocytes were replaced by ST2 KO monocytes. Macrophages treated with IL-33 reduced in vitro barrier leakage and maintained tight junction integrity after OGD. In contrast, IL-33 exerted minimal direct effects on the endothelial barrier in the absence of macrophages. IL-33-treated macrophages demonstrated transcriptional upregulation of an array of protective factors, suggesting a shift towards favorable phenotypes. Conclusion: Our results demonstrate that early-stage IL-33/ST2 signaling in infiltrating macrophages reduces the extent of acute BBB disruption after stroke. Intranasal IL-33 administration may represent a new strategy to reduce BBB leakage and infarct severity. [ABSTRACT FROM AUTHOR]

Background and purpose: We aimed to investigate the association between critical perfusion delay and poor outcome among recanalized stroke patients with anterior large-vessel occlusion, and to use pretreatment hypoperfusion biomarkers on CT to predict futile recanalization even after successful thrombectomy. Methods: An ischemic region with time-to-maximum (Tmax) > 12s–10s was defined as critical hypoperfusion, Tmax > 8s as moderate hypoperfusion, and hypoperfusion intensity ratio (HIR, volumetric ratio of Tmax > 10s / Tmax > 6s) represented for severity of critical hypoperfusion and rCBF < 30% for ischemic core. The associations between these CT perfusion characteristics and favorable or unfavorable outcome (mRS 0–2 versus 3–6) were analyzed in univariable regression, and a multivariable model was then used to predict futile recanalization. Results: Seventy-nine stroke patients were included and had good grades of instant recanalization. Forty-two patients (53%) had poor outcomes, and they had a significantly larger volume of critical hypoperfusion as seen with Tmax > 10s and > 12s (P = 0.032 and 0.008, respectively), a larger volume of ischemic core (P = 0.011) and a higher HIR (P = 0.002) than those patients achieving good outcomes. In the univariable analysis, a lower HIR (OR, 0.008; 95%CI, 0.001–0.254, P = 0.006) was associated with favorable outcome. The volume size of Tmax > 12s was significantly and positively correlated with the size of ischemic core. A HIR value higher than 0.491 might predict a futile recanalization and poor outcome (AUC = 0.701). Conclusions: The critical hypoperfusion biomarkers on CTP could be useful in triaging endovascular treatment and identifying stroke patients at risk of futile recanalization. [ABSTRACT FROM AUTHOR]

Background: A high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear. Methods: Study data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed. Results: Deaths and DALYs increased worldwide from 1990–2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24–-0.96) and 0.04 (95% CI:-0.47–0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P < 0.001) and the SDI in 2021 in different countries (R = -0.66, P < 0.001); these patterns were similar to those of the ASDR; the HDI in 2021 was associated with the ASMR-related EAPC (R = -0.71, P < 0.001) and the ASDR-related EAPC in different countries (R = -0.71, P < 0.001). Conclusions: The number of deaths and DALYs from ischemic stroke attributable to hBMI worldwide increased substantially from 1990–2021. Successful population-wide initiatives targeting hBMI may mitigate a wide range of burdens on this disease. Taking into account variations in the SDI burden, future prevention and control strategies must be developed and implemented according to country-specific development status. [ABSTRACT FROM AUTHOR]

Background: Post-stroke stress can trigger instant survival but its influence on long-term ischemic stroke outcomes remains controversial. Thus, we sought to explore the associations of acute post-stroke stress evidenced by endocrine and metabolic changes, with long-term ischemic stroke outcomes. Methods: Admissions for acute ischemic stroke within seven days of onset were prospectively recruited to determine acute endocrine and metabolic variations measured by thyroid parameters and the stress hyperglycemia ratio (SHR). Long-term ischemic stroke prognoses were followed up for one year, with the primary outcome being a modified Rankin Scale score of 3 to 6. Results: A total of 887 patients were enrolled, of which 535 reached the final one-year followed up at a poor prognosis rate of 29.3%. Patients with poor outcomes were observed to have lower levels of free triiodothyronine (fT3) and higher levels of SHR on admission. Medium values (fT3, 4.4 mmol/L; SHR, 8 nmol/L) were used to divide patients into four gradient stress degrees. Larger acute endocrine and metabolic variations (fT3 < 4.4 mmol/L and SHR ≥ 8 nmol/L) were independently associated with a poor one-year prognosis (adjusted OR = 4.231, P = 0.001). Conclusions: High degrees of acute post-stroke stress may aggravate long-term ischemic stroke prognosis and timely stress-reduced interventions may help promote post-stroke living quality is equally important as survival. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia is one of the most common comorbidities in patients with acute ischemic stroke (AIS). This study aimed to assess the impact of short-term longitudinal blood glucose level change trajectories on the 30-day mortality risk in patients with AIS. Methods: Data for AIS patients were obtained from the 2001–2019 Medical Information Mart for Intensive Care (MIMIC) database. The latent growth mixture modeling (LGMM) was utilized to classify a patient's blood glucose level trajectory within 24 h of admission. Cox regression analyses were applied to examine the relationship between blood glucose levels at admission and blood glucose level trajectories and the risk of 30-day mortality in patients with AIS. Results: A total of 2,432 patients with AIS were included in this retrospective cohort study, with 30-day mortality occurring in 574 (23.60%) patients. The median glucose levels of all patients were 136.00 (110.00, 178.00) mg/dL. Four blood glucose level trajectories were identified: low level-stable trend (type 1), moderate level-stable trend (type 2), high level-decreasing-increasing trend (type 3), and moderate level-increasing-decreasing trend (type 4). Type 2 blood glucose level trajectory was associated with an increased risk of 30-day mortality compared with type 1 blood glucose level trajectory [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 1.03–1.59), but there were no significant associations between type 3 (HR = 1.16, 95%CI: 0.77–1.74) and type 4 (HR = 1.44, 95%CI: 0.84–2.45) trajectories and 30-day mortality risk. Subgroup analysis demonstrated that the association between type 2 trajectory and 30-day mortality risk was observed in patients aged ≥ 65 years (HR = 1.37, 95%CI: 1.05–1.79), female (HR = 1.42, 95%CI: 1.05–1.94), with (HR = 1.44, 95%CI: 1.02–2.02) or without (HR = 1.42, 95%CI: 1.01–1.99) diabetes, and not using insulin (HR = 2.80, 95%CI: 1.43–5.49). Conclusion: AIS patients with consistently high blood glucose levels within 24 h of admission increased the risk of 30-day mortality. [ABSTRACT FROM AUTHOR]

Background: Congenital agenesis of internal carotid artery (ICA) is a rare cerebrovascular variation entity. Most cases of congenital ICA agenesis are asymptomatic and discovered incidentally. Congenital ICA agenesis presenting as ischemic stroke is even rare. Case presentation: An 80-year-old male patient was admitted to our hospital due to sudden dysarthria and left limb weakness for 3.5 h. Based on emergency physical examination and head computed tomography (CT) scan results, acute ischemic stroke (AIS) of right cerebral hemisphere was suspected. Following intravenous thrombolysis with recombinant tissue plasminogen activator, right congenital agenesis of ICA was confirmed by CT and digital subtraction angiography. Additionally, there was a severe right vertebral artery ostial (VAO) stenosis. After ruling out common causes of AIS such as haematological diseases, arterial dissection, organic heart disease, immunological abnormality and underlying possible malignancies, we hypothesize that the severe stenosis of the right VAO may have contributed to the development of AIS in this case. Conclusions: We present a case of right congenital ICA agenesis in which severe stenosis of the right VAO may have played a role in the development of AIS. This case underscores a rare scenario where a lesion in the posterior circulation leads to an infarction in the anterior circulation in the setting of congenital ICA agenesis. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is known for its high morbidity, disability and mortality rates, and studies designed to explore its pathophysiological mechanisms and identify novel therapeutic strategies are urgently needed. We aimed to probe the effects of the deubiquitinase OTUD3-IRP2-p53/PTGS2 pathway on cerebral ischemia‒reperfusion (I/R) injury and hippocampal neuron ferroptosis. Methods: A cerebral I/R mouse model was established. Furthermore, lentiviral vectors that overexpressed OTUD3 and knocked down IRP2 were constructed, and a series of assays were performed to probe the OTUD3/IRP2/p53/PTGS2 mechanism. An oxygen‒glucose deprivation and reoxygenation (OGD/R) model of mouse hippocampal neurons was constructed. Then, OTUD3 and IRP2 were knocked down and overexpressed, and p53 was overexpressed to explore the mechanism of the OTUD3/IRP2/p53/PTGS2 pathway. Results: OTUD3 and IRP2 were expressed at low levels in cerebral I/R models. OTUD3 promoted IRP2 expression to protect damaged hippocampal neurons. Moreover, IRP2 affected ferroptosis in hippocampal neurons. In addition, IRP2 inhibited p53. After IRP2 and p53 were overexpressed, IRP2 regulated the p53/PTGS2 pathway and affected ferroptosis in hippocampal neurons. In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway. Conclusions: The deubiquitinase OTUD3 stabilized IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to subsequently ameliorate cerebral I/R injury. [ABSTRACT FROM AUTHOR]

Background: Endovascular therapy (EVT) is the treatment of choice for acute ischemic stroke (AIS) with large vessel occlusion. However, in many patients, successful EVT recanalization does not correspond to a clinical improvement, called futile recanalization (FR). We aimed to identify stroke risk factors and patient characteristics associated with FR in AIS with large core infarct (LCI). Methods: A total of 137 patients with AIS with LCI treated by EVT at a single stroke center were retrospectively included from January 2016 to June 2023. LCI was defined by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECT) < 6. Patient age, sex, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), time to treatment, risk factors, and radiologic findings were collected, and potential associations with FR were analyzed. FR was defined as successful reperfusion with modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b but without functional independence at 90 days (mRS ≥ 3). A multivariate logistic regression analysis was conducted on the clinical characteristics of patients, based on the presence or absence of FR, and the factors influencing FR. Results: Of 137 patients, 120 showed successful recanalization (mTICI ≥ 2b). All patients were divided into FR (n = 80) and no FR (n = 40) groups. Older age (odds ratio [OR] 1.052, 95% confidence interval [CI] 1.002–1.105; p = 0.041), the higher the initial NIHSS score (OR 1.181, 95% CI 1.037–1.344; p = 0.012), and prior intravenous plasminogen activator (OR 0.310, 95% CI 0.118–0.813, p = 0.017) were independent influencing factors of FR. Conclusions: The older age, the higher the initial NIHSS, and not receiving intravenous plasminogen activator were independently associated with FR in AIS with LCI. These factors could identify poor responders to EVT recanalization. [ABSTRACT FROM AUTHOR]

Background: Excessive daytime sleepiness (EDS) is a common complication of stroke that has a detrimental effect on patients' daily life and functional recovery. The clinical characteristics and risk factors for poststroke EDS may differ between males and females. Methods: A retrospective study based on hospital medical records was conducted on patients with a diagnosis of stroke who participated in polysomnographic monitoring at the Affiliated Hospital of Yangzhou University from February 2022 to May 2024. Baseline data, laboratory test data, polysomnographic data, and related scale scores were retrospectively collected. The Epworth Sleepiness Scale (ESS) score was used to assess EDS after stroke. Binary logistic regression was used to determine the risk factors for daytime sleepiness. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Statistical analysis was performed via IBM SPSS 26.0. Results: ESS scores were higher in males than in females, whereas females had higher Pittsburgh Sleep Quality Index (PSQI) scores and Hospital Anxiety and Depression Scale (HADS) scores. Male sex and higher depression scores were risk factors for EDS; among male patients, higher anxiety scores were a risk factor for EDS, whereas smoking was a protective factor. Depression, a higher arousal index and a reduced proportion of N3 sleep periods were risk factors for EDS in females. Conclusions: The characteristics and influencing factors of EDS differ between the sexes in patients with mild and moderate ischaemic stroke. Our study may provide evidence and guidance for clinical diagnosis and treatment. Interventional studies are needed to assess the impact of treating these risk factors in the future. [ABSTRACT FROM AUTHOR]

Background: Endovascular thrombectomy (EVT) has emerged as the established standard of care for the treatment of anterior circulation large-vessel occlusion (LVO). However, its benefits remain unclear in specific patient populations. Herein, we present an updated systematic review and meta-analysis aimed at thoroughly assessing the effectiveness and safety of combining EVT with medical treatment (MT) compared with MT alone. Methods: This systematic review was performed in accordance with the PRISMA guideline. The MEDLINE, Embase, and Cochrane databases were systematically searched to identify relevant articles published until December 30, 2023. The inclusion criteria restricted articles to randomized clinical trials (RCTs). We pooled odds ratios (OR) and their respective 95% confidence intervals (CIs). Results: Fifteen RCTs involving 3897 patients were included in the study. EVT plus MT was associated with a significant reduction in disability at 90 days (OR = 1.91, [1.61–2.26]), improved functional independence (modified Rankin Scale [mRS] 0–2) (OR = 2.19 [1.81–2.64]), excellent functional outcomes (mRS 0–1) (OR = 2.37, [1.45–3.87]), improved independent ambulation (mRS 0–3) (OR = 2.17, [1.75–2.69]), and higher rates of partial/complete recanalization (OR = 2.18, [1.66–2.87] compared with EVT. Efficacy outcomes for both large and small infarct cores were statistically favorable following EVT. Safety outcomes showed comparable rates, except for intracerebral and subarachnoid hemorrhage, which favored MT alone. Conclusion: This meta-analysis supports the use of EVT plus MT as the standard of care for acute ischemic stroke patients with LVO of any infarct core size, as it offers substantial improvements in functional outcomes and recanalization. Safety considerations, particularly the risk of hemorrhage, warrant careful patient selection. These findings provide valuable insights for optimizing stroke management protocols and enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Stroke-associated pneumonia (SAP) is a common complication in stroke patients, and the Barthel Index (BI) is a well-established metric for assessing activities of daily living (ADL). However, the association between BI and SAP in acute ischemic stroke (AIS) patients remains unclear. This study aims to investigate the relationship between BI at admission and SAP, and explore the factors in AIS elderly patients. Method: Retrospective data were collected from ischemic stroke patients hospitalized at the Second Affiliated Hospital of Nanchang University between January 2018 and July 2021, including their basic demographic and laboratory test results. Restricted cubic spline regression, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to investigate the relationship between BI and SAP. Additionally, the Shapley Additive exPlanations (SHAP) method was used to identify the factors influencing SAP. Results: The study included 7,548 eligible stroke patients with a mean age of 75.1 ± 7.6 years, among which 41.14% were female. The SAP group demonstrated significantly lower BI compared to the non-SAP group (50.86 ± 35.60 vs. 75.27 ± 26.33, P < 0.001). Additionally, a conspicuous trend of decreasing SAP risk across the Q1-4 groups was observed (P < 0.001). The RCS analysis further confirmed a gradual reduction in SAP risk with increasing BI. Based on the clinical model, both the BI (NRI = 0.014, P = 0.005; IDI = 0.04, P < 0.001) and the NIHSS score (NRI = 0.09, P = 0.03; IDI = 0.025, P < 0.001) demonstrated additional predictive value for SAP. Multivariate logistic regression and SHAP analysis identified WBC, CONUT, TG, UA, and RBC levels, as well as the type of health insurance (urban employee basic medical insurance), as important independent predictors of SAP. Conclusion: BI at admission constitutes a risk factor for the onset of SAP in elderly patients with AIS, Compared to the NIHSS and mRS score, BI may be a more reliable and practical predictor of SAP. [ABSTRACT FROM AUTHOR]

The aberrant acetylation of mitochondrial proteins is involved in the pathogenesis of multiple diseases including neurodegenerative diseases and cerebral ischemic injury. Previous studies have shown that depletion of mitochondrial NAD+, which is necessary for mitochondrial deacetylase activity, leads to decreased activity of mitochondrial deacetylase and thus causes hyperacetylation of mitochondrial proteins in ischemic brain tissues, which results in altered mitochondrial dynamics. However, it remains largely unknown about how mitochondrial dynamics-related protein Drp1 is acetylated in ischemic neuronal cells and brain tissues. Here, we showed that Drp1 and GCN5L1 expression was up-regulated in OGD-treated neuronal cells and ischemic brain tissues induced by dMCAO, accompanied by the increased mitochondrial fission, mtROS accumulation, and cell apoptosis. Further, we confirmed that ischemia/hypoxia promoted Drp1 interaction with GCN5L1 in neuronal cells and brain tissues. GCN5L1 knockdown attenuated, while its overexpression enhanced Drp1 acetylation and mitochondrial fission, indicating that GCN5L1 plays a crucial role in ischemia/hypoxia-induced mitochondrial fission by acetylating Drp1. Mechanistically, ischemia/hypoxia induced Drp1 phosphorylation by CDK5 upregulation-mediated activation of AMPK in neuronal cells, which in turn facilitated the interaction of GCN5L1 with Drp1, thus enhancing Drp1 acetylation and mitochondrial fission. Accordingly, inhibition of AMPK alleviated ischemia/hypoxia- induced Drp1 acetylation and mitochondrial fission and protected brain tissues from ischemic damage. These findings provide a novel insight into the functional roles of GCN5L1 in regulating Drp1 acetylation and identify a previously unrecognized CDK5-AMPK-GCN5L1 pathway that mediates the acetylation of Drp1 in ischemic brain tissues. [ABSTRACT FROM AUTHOR]

Background: Prediction of short-term outcomes in young patients with acute ischemic stroke (AIS) may assist in making therapy decisions. Machine learning (ML) is increasingly used in healthcare due to its high accuracy. This study aims to use a ML-based predictive model for poor 3-month functional outcomes in young AIS patients and to compare the predictive performance of ML models with the logistic regression model. Methods: We enrolled AIS patients aged between 18 and 50 years from the Third Chinese National Stroke Registry (CNSR-III), collected between 2015 and 2018. A modified Rankin Scale (mRS) ≥ 3 was a poor functional outcome at 3 months. Four ML tree models were developed: The extreme Gradient Boosting (XGBoost), Light Gradient Boosted Machine (lightGBM), Random Forest (RF), and The Gradient Boosting Decision Trees (GBDT), compared with logistic regression. We assess the model performance based on both discrimination and calibration. Results: A total of 2268 young patients with a mean age of 44.3 ± 5.5 years were included. Among them, (9%) had poor functional outcomes. The mRS at admission, living alone conditions, and high National Institutes of Health Stroke Scale (NIHSS) at discharge remained independent predictors of poor 3-month outcomes. The best AUC in the test group was XGBoost (AUC = 0.801), followed by GBDT, RF, and lightGBM (AUCs of 0.795, 0, 794, and 0.792, respectively). The XGBoost, RF, and lightGBM models were significantly better than logistic regression (P < 0.05). Conclusions: ML outperformed logistic regression, where XGBoost the boost was the best model for predicting poor functional outcomes in young AIS patients. It is important to consider living alone conditions with high severity scores to improve stroke prognosis. [ABSTRACT FROM AUTHOR]

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members. Case presentation: We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism. Conclusions: When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn't be missed in the evaluation of embolic sources. [ABSTRACT FROM AUTHOR]

Background: Stroke is a major cause of illness, death, and long-term disability and a major health concern worldwide. Experts consider insulin resistance (IR), a defining feature of the metabolic syndrome and a significant risk factor for stroke. Insulin resistance, or IR, is common among stroke patients. The triglyceride-glucose (TYG) index's relevance to both lipotoxicity and glucotoxicity has led to its proposal as an alternative indicator of IR. Aim: Examining the connection between elevated TYG INDEX scores and worse clinical outcomes in ischemic stroke patients is the main goal. Finding out how often bad outcomes (recurrence and all-cause death) are in ischemic stroke patients is the secondary goal. Method: This was a retrospective observational study that involved patients admitted to the 850-bed Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, a tertiary care teaching hospital located in the Krishna district of Andhra Pradesh (India). The study was conducted over a period of six months. All the 95 patients who satisfied the eligibility criteria were included. The patients' TYG INDEX values were first determined and patients with ischemic stroke who had elevated TYG INDEX values were then compared for clinical outcomes including recurrence and all-cause death with ischemic patients with normal TYG INDEX. Results: In this study, the total cholesterol of the patients (mean ± SD) was 165.01 ± 51.5 mg/dL; Triglycerides was 157.031 ± 98.9 mg/dL; HDL-c was 37.253 ± 5.52 mg/dl; LDL-c was 107 ± 48.3 mg/Dl; and FBS was 153.74 ± 71.52 mg/dL. The chi-square test showed that only FBS, Triglyceride, and Total cholesterol were significantly associated with TYG INDEX whereas other variables like age, LDL, and HDL were not. There was no significant association between the TYG INDEX and clinical outcomes of ischemic stroke. In both groups of patients, risk and no risk TYG INDEX values, the mRS score showed variable and unpredictable relationship with the TYG INDEX. Conclusion: Contrary to the few studies that discovered one, our research leads us to the conclusion that there may not be a relevant association between the TYG INDEX and clinical results in patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: As a supportive treatment, the effectiveness of oxygen therapy in ischemic stroke (IS) patients remains unclear. This study aimed to evaluate the relationships between arterial partial pressure of oxygen (PaO2) and both consciousness at discharge and all-cause mortality risk in ICU IS patients. Methods: Blood gas measurements for all patients diagnosed with IS were extracted from the MIMIC-IV database. Patients were classified into four groups based on their average PaO2 during the first ICU day: hypoxemia (PaO2 < 80 mmHg), normoxemia (PaO2 80–120 mmHg), mild hyperoxemia (PaO2 121–199 mmHg), and moderate/severe hyperoxemia (PaO2 ≥ 200 mmHg). The primary endpoint was 90-day all-cause mortality. Secondary outcomes included the level of consciousness at discharge, assessed by the Glasgow Coma Scale (GCS), and 30-day all-cause mortality. Multivariate Cox regression and Restricted cubic spline (RCS) analysis were used to investigate the relationship between mean PaO2 and mortality, and to assess the nonlinear association between exposure and outcomes. Results: This study included a total of 946 IS patients. The cumulative incidence of 30-day and 90-day all-cause mortality increased with decreasing PaO2 levels. RCS analysis revealed a nonlinear relationship between PaO2 and the risk of 30-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001), as well as a nonlinear association between PaO2 and 90-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001). The results remained consistent after excluding the small subset of patients who received reperfusion therapy. Sensitivity analysis indicated that the favorable impact on survival tends to increase with the extended duration of elevated PaO2. Conclusions: For IS patients who do not receive reperfusion therapy or whose recanalization status is unknown, a lower PaO2 early during ICU admission is considered an independent risk factor for short-term and recent mortality. Adjusting respiratory parameters to maintain supraphysiological levels of PaO2 appears to be beneficial for survival, although this finding requires further validation through additional studies. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death worldwide, with oxidative stress and calcium overload playing significant roles in the pathophysiology of the disease. Ozone, renowned for its potent antioxidant properties, is commonly employed as an adjuvant therapy in clinical settings. Nevertheless, it remains unclear whether ozone therapy on parthanatos in cerebral ischemia–reperfusion injury (CIRI). This study aims to investigate the impact of ozone therapy on reducing parthanatos during CIRI and to elucidate the underlying mechanism. Methods: Hydrogen peroxide (H2O2) was utilized to mimic the generation of reactive oxygen species (ROS) in SH-SY5Y cell reperfusion injury in vitro, and an in vivo ischemic stroke model was established. Ozone saline was introduced for co-culture or intravenously administered to mice. Apoptosis and oxidative stress were assessed using flow cytometry and immunofluorescence. Western blotting was utilized to examine the expression of parthanatos signature proteins. The mechanism by which ozone inhibits parthanatos was elucidated through inhibiting PPARg or Nrf2 activity. Results: The findings demonstrated that ozone mitigated H2O2-induced parthanatos by either upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) or activating peroxisome proliferator-activated receptorg (PPARg). Furthermore, through the use of calcium chelators and ROS inhibitors, it was discovered that ROS directly induced parthanatos and facilitated intracellular calcium elevation. Notably, a malignant feedback loop between ROS and calcium was identified, further amplifying the induction of parthanatos. Ozone therapy exhibited its efficacy by increasing PPARg activity or enhancing the Nrf2 translation, thereby inhibiting ROS production induced by H2O2. Concurrently, our study demonstrated that ozone treatment markedly inhibited parthanatos in stroke-afflicted mice. Additionally, ozone therapy demonstrated significant neuroprotective effects on cortical neurons, effectively suppressing parthanatos. Conclusions: These findings contribute valuable insights into the potential of ozone therapy as a therapeutic strategy for reducing parthanatos during CIRI, highlighting its impact on key molecular pathways associated with oxidative stress and calcium regulation. [ABSTRACT FROM AUTHOR]

Background: S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. Methods: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. Results: A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659–51.048, P < 0.001; non-dominant: β 23.645, 95% CI 10.774–36.516, P = 0.007). However, serum S100β levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: β 3.470, 95% CI 2.392–4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936–10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: β 0.326, 95% CI − 0.735–1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538–1.445, P = 0.619). The association of S100β levels and HT was not significant in either stroke lateralization group. Conclusions: Serum S100β levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100β in judging the degree of disease and predicting prognosis. [ABSTRACT FROM AUTHOR]

Background: Optimal blood pressure management during endovascular stroke treatment is not certain. We hypothesized that time or proportion of intraprocedural systolic blood pressure spent in a range around admission blood pressure might be associated with better clinical outcome. Methods: We conducted a retrospective observational study at a single center at a university hospital, which included patients from August 2018 to September 2020 suffering from acute ischemic stroke with anterior circulation vessel occlusion and treated with endovascular therapy. Time and proportion of procedure time where systolic blood pressure (SBP) was near the baseline SBP on admission (bSBP) were used as exposure variables. The primary outcome was the occurrence of mRS score 0–2 three months after stroke. The primary analysis was performed by fitting a logistic regression model adjusted for baseline NIHSS, pre-stroke mRS, mTICI score, intubation, age and sex. Results: We included 589 patients in the analysis. Mean (SD) age was 76 (12) years, 315 were women (53%) and mean (SD) NIHSS score at admission was 15 (7.5). Mean (SD) bSBP was 167 (28) mmHg and mean (SD) intraprocedural SBP was 147 (21) mmHg. The proportion of time where intraprocedural SBP was in range of bSBP ± 20% was associated with a slightly higher odds of achieving favorable outcome (adjusted OR, 1.007; 95% CI, 1.0003–1.013). Conclusion: A higher proportion of intraprocedural time with systolic blood pressure in range of ± 20% of the admission level is associated with higher odds of favorable functional outcome. Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Neural stem cells (NSCs) play a crucial role in the progress of ischemic stroke. Research on zebrafish embryonic demonstrates an association between Strawberry Notch 1 (Sbno1) and central nervous system development. However, the regulation and underlying mechanism of Sbno1 in NSCs have not been studied yet. Here, we investigated the role and the mechanism of Sbno1 in NSCs development and the potential therapeutic value of Sbno1 in ischemic stroke. Methods: Adeno-associated virus (AAV) was used for overexpression or knockdown of Sbno1 in vitro or in vivo. A mouse model of MCAO was established to evaluate the neuroprotective effects of AAV-Sbno1, including balance beam test, rotarod test, and strength evaluation. H&E and immunofluorescence assessed neuronal impairment. Western blot and RT-qPCR were used to detect the expression of Sbno1 and its downstream target genes. RNA-seq and western blot were performed to explore further molecular mechanisms by which Sbno1 promoted endogenous repair of NSCs and macrophages M2 polarization. CCK8 was conducted to assess the effects of Sbno1 on NSCs proliferation. The impact of Sbno1 on NSCs apoptosis was evaluated by flow cytometry. NSCs derived from small extracellular vesicles (sEV) were obtained using ultracentrifugation and identified through nanoparticle tracking analysis (NTA) and western blot analysis. Results: Our results showed that Sbno1 is highly expressed in the central nervous system, which plays a crucial role in regulating the proliferation of NSCs through the PI3k-Akt-GSK3β-Wnt/β-catenin signaling pathway. In addition, with overexpression of Sbno1 in the hippocampus, post-stroke behavioral scores were superior to the wild-type mice, and immunofluorescence staining revealed an increased number of newly generated neurons. sEV released by NSCs overexpressing Sbno1 inhibited neuroinflammation, which mechanistically impaired the activation of the microglial NF-κB and MAPK signaling pathways. Conclusions: Our studies indicate that sbno1 promotes the proliferation of NSCs and enhances endogenous repairing through the PI3k-Akt-GSK3β-Wnt/β-catenin signaling pathway. Additionally, NSCs overexpressing sbno1 improve ischemic stroke recovery and inhibit neuroinflammation after ischemia by sEV through the MAPK and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Cardiac embolism plays a very significant role in acute ischemic strokes (AIS), constituting approximately one-third of cases. The origin of these emboli often stems from intracardiac thrombi in the left atrium or left ventricle. Utilizing the National Readmission Database from 2016 to 2019, we investigate the prevalence of cardiac thrombi in AIS patients and explore their potential correlation with endovascular thrombectomy (EVT) utilization, and mortality rates. Among 1,272,456 AIS patients, 0.6% had concurrent cardiac thrombus, with an increasing trend observed over the study period (P value < 0.001). The cardiac thrombus cohort showed a higher prevalence of comorbidities such as congestive heart failure and atrial fibrillation. After propensity-score matching, groups were well-balanced in terms of baseline characteristics. Patients within the cardiac thrombus cohort experienced a longer hospital stay (median 5 days vs. 3 days), but no significant difference in mortality was noted. Importantly, the cardiac thrombus cohort demonstrated a higher frequency of EVT utilization, suggesting a link to larger vessel occlusions. Despite matching based on atrial fibrillation, the EVT utilization in the cardiac thrombus cohort remained high, highlighting a significant association. While 30-day readmission rates were comparable, cardiac thrombus patients faced a higher risk of gastrointestinal bleeding and hemorrhagic stroke, likely attributed to anticoagulation use. Limitations include potential miscoding in the administrative database and a lack of detailed imaging findings. In conclusion, this study highlights the increased likelihood of EVT in AIS patients with cardiac thrombus, possibly indicative of larger vessel occlusion associated with cardiac thrombus. [ABSTRACT FROM AUTHOR]

Backgrounds: The impact of off-duty hours mechanical thrombectomy on outcomes remains a subject of controversy. The impacts of off-duty hours on procedures are influenced by various factors, but the most critical one is the time delay in initiating the procedure after the patient's arrival at the emergency room. Recently, a report suggested that the impact of time delay on post-procedural outcomes is evident in patients who arrive at the emergency room within 6 h of symptom onset, referred to as the "early window." We hypothesized that the impact of procedure delays on outcomes during off duty-hours would be most significant within this early window. This study aimed to investigate the impact of door-to-puncture time (DTPT) delays in patients who underwent mechanical thrombectomy for acute ischemic stroke (AIS) during off-duty hours in both the early and late time windows. Methods: We investigated patients who presented to the emergency center between 2014 and 2022. Among a total of 6,496 AIS patients, we selected those who underwent mechanical thrombectomy within 24 h of the onset of acute anterior circulation occlusion. The eligible patients were divided into two groups: those who arrived within 6 h of symptom onset and received the procedure within 8 h (early window), and those who received the procedure between 8 h and 24 h after symptom onset (late window). The study assessed the association between the onset to puncture time in each group and poor outcomes, measured by the modified Rankin scores(mRs) at 90 days. Furthermore, the study analyzed the impact of receiving the procedure during off-hours in both the early and late windows on outcomes. Specifically, the analysis focused on the impact of delayed DTPT in patients during off-duty hours on outcomes measured by the 90-days mRS. Results: Among the eligible patients, a total of 501 AIS patients underwent mechanical thrombectomy for acute anterior circulation occlusion within 24 h. Of these, 395 patients (78.8%) fell into the early window category, and 320 patients (63.9%) underwent the procedure during off-duty hours. In the early window, for every 60-minute increase in OTPT, the probability of occurrence a poor outcome at 90 days significantly increased in the fully adjusted model (OR = 1.21; 95% CI, 1.02 to 1.43; p = 0.03). In the early window, delayed procedures during off-duty hours (exceeding 103 min of DTPT) were identified as an independent predictor of poor outcomes (OR = 1.85; 95% CI, 1.05 to 3.24; p = 0.03). However, in the late window, there was no association between DTPT and outcomes at 90 days, and the impact of DTPT delays during off-hours was not observed. Conclusions: Through this study, it became evident that the impacts of off-duty hours in mechanical thrombectomy were most pronounced in the early window, where the impact of time delay was clear. Therefore, it is believed that improvements in the treatment system are necessary to address this issue. [ABSTRACT FROM AUTHOR]

Background: Despite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14). Methods: A Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs. Results: Base-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust. Conclusion: Compared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study. Trial registration: URL http://www.clinicaltrials.gov. Unique identifier NCT00554723 November 7, 2007. [ABSTRACT FROM AUTHOR]

Background: The ideal single antiplatelet therapy for long-term maintenance after coronary stenting remains uncertain. In a head-to-head comparison, we aimed to evaluate the efficacy and safety profile of aspirin and clopidogrel as monotherapies in this patient cohort. Method: We reviewed 1044 patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES) at the Department of Cardiovascular Medicine, Jinshan Hospital of Fudan University, between January 2019 and December 2021 and completed a 12-month Dual Antiplatelet Therapy (DAPT) treatment. They were divided into two groups: 582 were assigned to the aspirin group (100 mg/day) and 422 to the clopidogrel group (75 mg/day). The primary endpoint was the composite cardiac death, ischemic stroke, myocardial infarction, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. Secondary endpoint events included all-cause death, ischemic stroke, myocardial infarction, bleeding (defined as a BARC type ≥ 2 bleeding), and gastrointestinal complications. Results: After a mean observation period of 25 ± 8.4 months, the primary endpoint event occurred in 29 (6.8%) patients in the clopidogrel group and 30 (5.1%) in the aspirin group, with no difference between the two groups (P = 0.253). In BARC type 2 or greater bleeding events, there were 9 (1.5%) in the aspirin group compared to 7 (1.7%) in the clopidogrel group, with no difference between the two groups (P = 0.160). Conclusion: After 12-month DAPT in Chinese patients undergoing DES implantation, aspirin monotherapy versus clopidogrel monotherapy showed no significant difference between the two drugs in terms of safety and efficacy in terms of hemorrhage, myocardial infarction, ischemic stroke, cardiac death, and bleeding with BARC type 2 or greater. [ABSTRACT FROM AUTHOR]

Background: Base excess (BE) is associated with mortality from many diseases. However, the relationship between BE and mortality in patients with ischemic stroke remains uncertain. Our aim is to investigate the relationship between BE values upon admission to the ICU and mortality rates in critically ill stroke patients. Methods: The current study enrolled 1,572 patients with ischemic stroke (863 males and 709 females). The associations of BE with intensive care unit (ICU), hospital, 28-day, and 1-year mortalities were assessed using multivariable logistic regression or Cox proportional hazards model. The potential impact of the Sequential Organ Failure Assessment (SOFA) score (< 5 or ≥ 5) on the prognostic value of BE was further evaluated with interaction and subgroup analyses. Results: BE values less than − 3 mmol/L, greater than 3 mmol/L, and within − 3 to 3 mmol/L (normal BE) were observed in 316 (20.1%), 175 (11.1%), and 1,081 (68.8%) patients, respectively. The restricted cubic splines analyses revealed that a U-shaped curve between BE and the mortality risk. Multivariable analysis indicated that patients with low BE (<-3 mmol/L) had higher rates of ICU mortality (odds ratio [OR], 1.829; 95% confidence interval [CI], 1.281–2.612; P = 0.001), hospital mortality (OR, 1.484; 95% CI, 1.077–2.045; P = 0.016), 28-day mortality (hazard ratio [HR], 1.522; 95% CI, 1.200–1.929; P = 0.001), and 1-year mortality (HR, 1.399; 95% CI, 1.148–1.705; P = 0.001) than patients with normal BE. Subgroup analyses showed consistent results pertaining to SOFA scores ≥ 5. Conclusions: In critically ill patients with ischemic stroke, an initial BE of <-3 mmol/L at ICU admission may indicate an increased risk of ICU, hospital, 28-day, and 1-year mortalities. [ABSTRACT FROM AUTHOR]

Background: Carotid artery dissection is an important cause of stroke. However, the predictors of ischemic stroke in patients with carotid artery dissection are controversial. The study aimed to analyze the predictors of ischemic stroke in patients with carotid artery dissection through retrospective medical records. Methods: Data of discharged patients diagnosed with carotid artery dissection during 2019–2023 were retrospectively collected. Based on the occurrence of ischemic stroke, the patients were divided into the ischemic stroke or non-ischemic stroke groups. Based on the results of univariate analyses, variables with an associated P value < 0.05 were introduced into the multivariable logistic regression analysis.. Results: A total of 165 patients were included in the study, with an average age of 55.00 (48.00, 66.00) years, including 86 patients with internal carotid artery dissection and 79 patients with vertebral artery dissection. Ischemic stroke occurred in 69 patients with carotid artery dissection. Multivariate logistic regression analysis indicated that diabetes (odds ratio [OR]: 3.144, 95% confidence interval [CI]: 1.552–6.508, P<0.002) and high white blood cells count (OR: 1.157, 95% CI: 1.02–1.327,P = 0.028) were related to the incidence of ischemic stroke in patients with carotid artery dissection. Conclusion: Ischemic stroke caused by carotid artery dissection causes severe damage to the nervous system. This study found that diabetes and high white blood cells count were associated with the incidence of ischemic stroke in patients with carotid artery dissection. Therefore, monitoring and controlling blood glucose levels and infections is essential in patients with carotid artery dissection to reduce the incidence of stroke. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke belongs to "apoplexy" and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke. Materials and methods: Middle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke. Results: BHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood–brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke. Conclusion: BHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology. [ABSTRACT FROM AUTHOR]

Introduction: Hospital overcrowding where patient admissions exceed capacity is associated with worse outcomes in Emergency Department. Developments in emergency stroke care have been associated with improvements in stroke outcome but are dependent on effective, organised care. We examined if overcrowding in the hospital system was associated with negative changes in stroke outcome. Methods: Data on overcrowding were obtained from the Irish Nurses and Midwives Organisation (INMO) 'Trolley Count' database recording the number of patients cared for on trolleys/chairs in all acute hospitals each midnight. These were compared with quarterly data from the Irish National Audit of Stroke from 2013 to 2021 inclusive. Variables analysed were inpatient mortality rate, thrombolysis rate for ischaemic stroke, median door to needle time and median length of stay. Results: 579449 patient episodes were recorded by Trolley Watch over the period, (Quarterly Median 16719.5, range 3389–27015). Average Quarterly Thrombolysis rate was 11.3% (sd 1.3%) Median Quarterly Inpatient Mortality rate was 11.8% (Range 8.9-14.0%). Median Quarterly Length of stay was 9 days (8–11 days). Median quarterly door to needle was 65 min (45–80 min). Q1 was typically the worst for overcrowding with on average 19777 incidences (sd 4786). This was significantly higher than for Q2 (mean 13540 (sd 4785) p = 0.005 t-test) and for Q3 (mean 14542 (sd 4753) p = 0.03). No significant correlation was found between quarterly Trolley watch episodes and inpatient mortality (r = 0.084, p = 0.63), median length of stay r=-0.15, p = 0.37) or thrombolysis rate (r = 0.089 p = 0.61). There was an unexpected significant negative correlation between trolley watch data and median door to needle time (r=-0.36, p = 0.03). Conclusion: Despite increasing hospital overcrowding, stroke services still managed to preserve standard of care. We could find no association between levels of overcrowding and deterioration in selected indices of patient care. [ABSTRACT FROM AUTHOR]

Background: The patent foramen ovale (PFO) and interatrial block (IAB) are associated with cryptogenic stroke (CS). However, the role of the interaction between PFO and IAB in CS remains unclear. Methods: This case–control study enrolled 256 patients with CS and 156 individuals without a history of stroke or transient ischemic attack. IAB was defined as P wave duration > 120 ms. PFO was evaluated by contrast transesophageal echocardiography, and classified as no-PFO, low-risk PFO and high-risk PFO. Multiplicative and additive interaction analysis were used to assess the interaction between PFO and IAB in CS. Results: Multiplicative interaction analysis unveiled a significant interaction between IAB and low-risk PFO in CS (OR for interaction = 3.653, 95% CI, 1.115–12.506; P = 0.037). Additive interaction analysis indicated that 68.4% (95% CI, 0.333–1.050; P < 0.001) of the increased risk of CS related to low-risk PFO was attributed to the interaction with IAB. The results were robust in multivariate analysis. However, but no significant multiplicative or additive interaction was observed between IAB and high-risk PFO. When stratified by IAB, high-risk PFO was associated with CS in both patients with IAB (OR, 4.186; 95% CI, 1.617–10.839; P = 0.003) and without IAB (OR, 3.476; 95% CI, 1.790–6.750; P < 0.001). However, low-risk PFO was only associated with CS in patients with IAB (OR, 2.684; 95% CI, 1.007–7.149; P = 0.048) but not in those without IAB (OR, 0.753; 95% CI, 0.343–1.651; P = 0.479). Conclusion: The interaction between IAB and PFO might play an important role in CS, particularly in cases with low-risk PFO. [ABSTRACT FROM AUTHOR]

Background: Associations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH). Aim: The associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively. Methods: We have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode. Results: One hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (β = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (β = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (β = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (β = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (β = 1.88, 95% CI: -0.10, 3.86; P = 0.0649). Conclusion: We observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c. [ABSTRACT FROM AUTHOR]

Background: There are significant sex differences in the incidence of stroke or diabetes mellitus. However, little is known about sex differences in stroke rehospitalization among diabetic patients. Object: To explore the sex differences in short-term and long-term rehospitalization of ischemic stroke patients with Type 2 diabetes mellitus. Methods: A retrospective cohort study was conducted from 2017 to 2021. The rehospitalization events of ischemic stroke patients with diabetes mellitus were identified by the national unified Electronic Health Record. Propensity score matching was applied to adjust for multiple covariates, and LASSO regression was used to screen for independent variables. Cox proportional hazards model was utilized to analyze the different sex in short-term (90 days, 1 year) and long-term (5 years) rehospitalization in ischemic stroke patients with type 2 diabetes mellitus. Result: A total of 10,724 ischemic stroke patients were included in this study, of whom 5,952 (55.5%) were males. After a 1:1 propensity score matching, there were 3,460 males and 2,772 females. After adjusting for confounding factors, female patients with type 2 diabetes had an increased risk of ischemic stroke rehospitalization at 90 days (HR: 1.94, 95%CI: 1.13–3.33, P < 0.05), 1 year (HR: 1.65, 95%CI:1.22–2.23, P = 0.001), and 5 years (HR: 1.58, 95%CI: 1.26–1.97, P < 0.001). However, there was no significant relationship between male patients with type 2 diabetes and the risk of ischemic stroke rehospitalization, either in the short or long term. Conclusion: Females with type 2 diabetes mellitus have a higher risk of ischemic stroke rehospitalization in both the short-term and long-term. [ABSTRACT FROM AUTHOR]

Background: Amantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients. Methods: Retrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine (N = 34) in the years 2016–2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models. Results: There were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9–14) than nonresponders (median = 9, IQR = 8–10, p = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [훃=1.02, 95% CI (0.10, 1.93), p = 0.031], but there was no significant associations with hospital day number started [훃=-0.003, 95% CI (-0.02, 0.02), p = 0.772]. Conclusions: Future randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients' determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials. [ABSTRACT FROM AUTHOR]

Background: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology. Objective: We aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization. Methods: This study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration. Results: A total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%). Conclusions: The ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients' etiology and initiate optimal strategies for secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) results from the rupture of blood vessels causing bleeding within the brain and is one of the major causes of death and long-term disability globally, particularly in low- and middle-income countries. Despite having a lower incidence than ischemic stroke, ICH imposes a greater social and economic burden. To our knowledge, since the release of the 2021 Global Burden of Disease (GBD) report, there has been no comprehensive update on the epidemiology and trends of ICH. This study aims to analyze the impact of gender, age, and the Sociodemographic Index (SDI) on the burden of ICH at global, regional, and national levels. Methods: Data on the incidence, deaths, and disability-adjusted life years (DALYs) of ICH and its related risk factors from 1990 to 2021 were extracted from the GBD 2021 project, encompassing 203 countries and regions. Furthermore, temporal trends of the global intracerebral hemorrhage burden were assessed through Joinpoint analysis. Results: In 2021, there were 3.444 million new cases of ICH worldwide, with an age-standardized prevalence rate of 40.8 per 100,000 people, representing a 31.4% decrease compared to 1990. In 2021, ICH caused 3.308 million deaths, with an age-standardized mortality rate of 39.1 per 100,000 people, a reduction of 36.6% since 1990. Globally, ICH accounted for 79.457 million DALYs, with an age-standardized DALY rate of 92.4 per 100,000 people, representing a 39.1% decrease since 1990. Regionally, Central Asia, Oceania, and Southeast Asia had the highest age-standardized prevalence rates of ICH, whereas Australasia, high-income North America, and Western Europe had the lowest rates. Nationally, the Solomon Islands, Mongolia, and Kiribati had the highest age-standardized prevalence rates, whereas Switzerland, New Zealand, and Australia had the lowest. Hypertension, smoking, and environmental pollution were identified as the primary risk factors for ICH. This study also validated the significant association between SDI and the burden of ICH, with the age-standardized DALY rate of ICH decreasing significantly as SDI increased. Conclusion: Despite the decreasing burden of intracerebral hemorrhage, it remains a significant public health issue in countries with a lower SDI. Prevention strategies should prioritize hypertension management, air quality improvement, and smoking control to further mitigate the impact of intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background: The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. Objectives: This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. Methods: This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. Results: Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. Conclusions: The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications. [ABSTRACT FROM AUTHOR]