Abstract Background and aims Minocycline is a promising anti-inflammatory agent for improving futile recanalization, but whether it improves clinical outcomes in basilar-artery stroke patients treated with endovascular therapy (EVT) remains unclear. In this study, we aimed to assess the efficacy and safety of oral minocycline combined with EVT on outcomes in patients who had basilar-artery stroke. Methods The Minocycline for acute Ischemic Stroke undergoing endovascular Treatment due to Basilar artery occlusion (MIST-B) trial was a multicenter, randomized, open-label clinical trial with blinded outcome assessment in 12 Chinese hospitals. Adults with basilar-artery stroke no more than 24 hours after onset were randomized (1:1) to receive oral minocycline (200 mg loading, then 100 mg every 12 hours for 5 days) plus EVT or EVT alone. The primary efficacy outcome was the expanded National Institutes of Health Stroke Scale (e-NIHSS) score at day 5. Results From March 4, 2023, to March 4, 2025, 90 patients were randomized, and 86 were analyzed (mean age 61.7 years, 31.4% women). At day 5, mean e-NIHSS was 15.0 (SD 13.5) in the minocycline group and 17.2 (SD 16.9) in the control group (adjusted mean difference -2.44 [95% CI -7.78 to 2.89]; P = 0.37). Other efficacy and safety outcomes, including symptomatic intracranial hemorrhage within 24 hours, 90-day modified Rankin Scale, did not differ significantly. Conclusions These results did not provide evidence to support prescribing minocycline to improve early neurological outcomes in patients with acute basilar-artery stroke undergoing EVT. Larger trials of minocycline with extended treatment duration are warranted. Conflict of interest All other authors declare no competing interests.

Objectives: To determine the long-term risk factors for rehemorrhage (primary outcome) in patients with ruptured brain arteriovenous malformations (BAVMs) after different treatment strategies and to evaluate the impact of different treatment strategies on lesion obliteration (secondary outcome) over a 10-year follow-up. Methods: This single-center retrospective cohort included 645 patients with ruptured brain arteriovenous malformations (BAVMs) treated between 2010 and 2019, with a median follow-up of 96 months. Patients were randomly divided into training (70%) and validation (30%) cohorts to identify and validate predictors of rehemorrhage-free survival (RFS). Cox regression analyses were performed to assess risk factors for RFS, while logistic regression and propensity score matching (PSM) were used to evaluate the impact of treatment strategies on obliteration and rehemorrhage. Results: Obliteration was observed in 66.0% (384/582) of the patients, and 109 patients (16.9%) experienced rehemorrhage. In the training set, the multivariate Cox regression analysis revealed that, deep location ((hazard ratio (HR) = 2.033, 95% confidence interval (CI) = 1.166-3.545; p = 0.012)/posterior location (HR=2.215, 95% CI=1.213-4.043; p = 0.010), lesion diameter >6 cm (HR = 4.901, 95% CI = 2.046-11.737; p < 0.001), and multiple drain veins (HR = 2.287, 95% CI = 1.207-4.335; p = 0.011), were significant independent risk factors for rehemorrhage-free survival. In the validation set, lesion diameters of 3-6 cm (HR = 4.910, 95% CI = 1.677-14.377; p = 0.004) and >6 cm (HR = 19.416, 95% CI = 5.152-73.173; p < 0.001) remained significant in the multivariate Cox regression analysis. After PSM, univariate logistic analysis revealed that, compared with radiosurgery, preradiosurgery embolization + radiosurgery resulted in a lower non-obliteration rate ((odd ratio) OR = 0.352, 95% CI = 0.134-0.926; p = 0.034). Conclusions: Lesion size, lesion location, and multiple draining veins were independently associated with long-term RFS. Preradiosurgical embolization improved the obliteration rate but did not significantly alter the risk of rehemorrhage. These findings directly inform treatment selection for ruptured BAVMs.

Minocycline is a promising anti-inflammatory agent for reducing futile recanalization, but whether it improves clinical outcomes in basilar-artery stroke patients treated with endovascular therapy (EVT) remains unclear. In this study, we aimed to assess the efficacy and safety of oral minocycline combined with EVT on outcomes in patients who had basilar-artery stroke. The Minocycline for acute Ischemic Stroke undergoing endovascular Treatment due to Basilar artery occlusion (MIST-B) trial was a multicenter, randomized, evaluator-blinded, open-label, pilot trial in 12 Chinese hospitals. Adults with basilar-artery stroke no more than 24 h after onset were randomized (1:1) to receive oral minocycline (200 mg loading, then 100 mg every 12 h for 5 days) plus EVT or EVT alone. The primary efficacy outcome was the expanded National Institutes of Health Stroke Scale (e-NIHSS) score at day 5; the primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 24 h. Participants were followed up 90 days after randomization. Modified intention-to-treat analysis examined treatment effect for the primary efficacy outcome using linear mixed models, with the baseline measurement of e-NIHSS score as a covariate. From March 4, 2023, to March 4, 2025, 90 patients were randomized, and 89 were analyzed (mean age 61.7 years, 31.5

OBJECTIVE:The aim of this study was to elucidate the adverse factors associated with brain arteriovenous malformation (BAVM)-related de novo headache after stereotactic radiosurgery (SRS) or microsurgery. BACKGROUND:There is a paucity of literature on posttreatment de novo headaches in initially headache-naïve patients who undergo treatment. METHODS:This retrospective cohort study analyzed patients aged 18 years or older who underwent SRS or microsurgery for a BAVM at our single center in Sichuan Province, China, between January 2010 and December 2019. Patients who did not present with headaches before treatment were included. Headache diagnosis and characteristics were performed according to the International Classification of Headache Disorders, 3rd edition criteria. The primary outcome was BAVM-related de novo headache after treatment. Statistical analysis was conducted on demographic, clinical, and radiographic characteristics to assess the distributions of the two groups of patients with and without posttreatment de novo headache. Subgroup analysis was further conducted on the SRS and microsurgery. RESULTS:Over the 10-year study period, we identified 194 patients with BAVM who presented without headache and who underwent SRS or microsurgery. Thirty-seven patients (19.1%) developed posttreatment de novo headache. In the SRS treatment cohort, statistically significant differences were detected between the headache and nonheadache subgroups with respect to the Spetzler-Martin (SM) grade (p = 0.018) and lesion diameter (p = 0.028). Multivariable logistic regression analysis confirmed that only the higher SM grade remained an independent adverse factor for de novo headache (adjusted odd ratio [OR] = 3.48, 95% confidence interval [CI] = 1.29-9.35, p = 0.013; high grade versus low grade BAVM). In the microsurgery treatment cohort, the lesion size in the de novo headache subgroup was significantly larger than that in the nonheadache subgroup, with a mean lesion diameter of 3.8 ± 0.3 cm versus 2.9 ± 0.2 cm (p = 0.024). Univariable logistic regression analysis revealed that only a larger diameter was significantly associated with increased odds of de novo headache (OR = 1.52, 95% CI = 1.04-2.21, p = 0.030; per 1 cm increase in diameter). CONCLUSION:In the microsurgery treatment subgroup, a larger BAVM was associated with increased odds of de novo headache (per 1 cm increase); in the SRS treatment subgroup, grades III-V were associated with increased odds of de novo headache.

Background Endothelial‐to‐mesenchymal transition (EndMT) is a key contributor to cardiac fibrosis, yet the role and underlying mechanisms of endothelial integrin β3 (ITGB3) activation in EndMT remain poorly understood. This study aims to explore the involvement of a novel ITGB3– CaMKIIα (calcium‐calmodulin–dependent protein kinase IIα)–CREB1 (cAMP‐responsive element binding protein) signaling axis in EndMT and to demonstrate that targeting endothelial ITGB3 mitigates pressure overload–induced heart failure (HF) by reducing cardiac fibrosis. Methods Endothelial‐cell–specific ITGB3 knockout mice were subjected to transverse aortic constriction to induce HF. Cardiac function, and the expression of EndMT‐associated genes were assessed to evaluate changes in cardiac remodeling. RNA sequencing and primary human endothelial cells and mouse cardiac microvascular endothelial cells were used to investigate downstream mechanisms. Additionally, the ITGB3‐specific inhibitor RGDfK was applied in the treatment of HF. Results The activation of ITGB3 was predominantly observed within endothelial cells. Endothelial cell–specific ITGB3 deletion attenuated cardiac dysfunction. Mechanistically, ITGB3 knockdown and CaMKII inhibition reduced CaMKII activation and subsequently lowered nuclear CREB1 phosphorylation levels. Reciprocally, the genetic overexpression of ITGB3 in endothelial cells increased EndMT by activating the CaMKIIα–CREB1 axis. These results were further substantiated by pharmacological studies with the ITGB3 specific cyclic‐RGD (Arg‐Gly‐Asp) peptide inhibitor (RGDfK). RGDfK treatment ameliorated pressure overload–induced cardiac remodeling and markedly improved cardiac function, establishing the disease‐specific role of ITGB3 in vivo. Conclusions This study demonstrates that endothelial ITGB3 regulates EndMT and contributes to the progression of pressure overload–induced HF, partly through the CaMKIIα–CREB1 signaling pathway. Targeting ITGB3 to inhibit EndMT may offer a promising therapeutic strategy for HF.

Background: Aortic dissection (AD) is a life-threatening vascular emergency with limited effective pharmacological treatments. Recent studies have identified Src homology 2 domain-containing transforming protein C1 (p66Shc) as a crucial mediator of oxidative stress, apoptosis, and inflammation in aortic cells, thereby contributing to cellular dysfunction and vascular remodeling implicated in AD development and progression. Despite its established role in promoting vascular dysfunction and remodeling, the protective potential of targeting p66Shc in AD remains unclear. Methods: We quantified activated protein C (aPC) levels in clinical plasma samples from control subjects and AD patients using enzyme-linked immunosorbent assay (ELISA). To evaluate changes in p66Shc expression, we analyzed aortic tissues by Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) staining. An in vivo AD model was established in thrombomodulin (TM)-mutant ApoE-/- mice, which display impaired TM-dependent PC activation, and exogenous PC was administered to evaluate its therapeutic effect. In parallel, mechanistic studies were performed in human endothelial cells using WB, co-immunoprecipitation (Co-IP), dual-label IF staining, chromatin immunoprecipitation (ChIP), luciferase reporter assays, and mitochondrial functional analyses. Results: In this study, we demonstrate that aPC, a coagulation protease with known cytoprotective properties, downregulates p66Shc expression through epigenetic modifications. Additionally, aPC can modulate the expression of a cold shock protein Y-box-binding protein 1 (YB1), which acts as a transcription factor, leading to elevated O-linked N-acetylglucosamine transferase (OGT) levels. This upregulation enhances the O-glycosylation of p66Shc on its 29th tyrosine residue, preventing its mitochondrial translocation, preserving mitochondrial membrane potential, and reducing reactive oxygen species (ROS) production. Consequently, these molecular mechanisms inhibit the onset and progression of AD. Conclusions: aPC epigenetically represses p66Shc transcription and promotes its O-glycosylation at Thr29 via the YB-1/OGT axis, thereby inhibiting mitochondrial ROS production and preventing vascular injury.

Background: The optimal timing for exchanging an endotracheal tube for a tracheostomy cannula in patients with hypoxic-ischaemic encephalopathy is controversial. Aim: This study aimed to evaluate the effects of early versus late tracheostomy on the prognosis of patients with hypoxic-ischaemic encephalopathy. Study Design: The study was an observational retrospective study that followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. We included adults with hypoxic-ischaemic encephalopathy who underwent tracheostomy between January 2012 and September 2020. The patients were classified into early or late tracheostomy groups. To eliminate differences in baseline characteristics, propensity score matching was conducted, and the outcomes between the two groups were compared. Results: A total of 132 patients were included, and through propensity score matching, 54 pairs of patients were matched. The early tracheostomy group showed a significant reduction in the duration of mechanical ventilation (median, 12 days; interquartile range 7-20 vs. median, 28 days; interquartile range, 15.75-58.25, p < .001), intensive care unit length of stay (median, 14.5 days; interquartile range, 6.75-26 vs. median, 35 days; interquartile range, 20-59, p < .001) and hospital length of stay (median, 19.5 days; interquartile range, 10.87-36.5 vs. median, 39.5 days; interquartile range, 22-66, p < .001). Over a 1-year follow-up period, there were no significant differences between the two groups regarding inhospital mortality (57.4% vs. 46.3%, p = .248), 30-day mortality (59.3% vs. 46.3%, p = .177) and 1-year mortality (61.1% vs. 48.1%, p = .176). Conclusions: In patients with hypoxic-ischaemic encephalopathy undergoing mechanical ventilation, early tracheostomy is associated with a reduction in the duration of mechanical ventilation and decreased intensive care unit and hospital length of stay. Relevance to Clinical Practice: For patients with hypoxic-ischaemic encephalopathy who are at a high risk of requiring prolonged mechanical ventilation, the benefits of early tracheostomy suggest considering it a viable treatment option.

In metabolic dysfunction-related steatohepatitis (MASH), ITGB3 promotes hepatic fibrosis via activating hepatic stellate cells, but whether it directly regulates hepatic lipid metabolism through membrane-scaffolding function and the underlying mechanisms remain unclear. Transcriptomic analyses of human and murine models of MASH revealed consistent upregulation of ITGB3 in hepatocytes. In mice, the hepatocyte-specific overexpression of ITGB3 exacerbates diet-induced obesity, insulin resistance, steatosis, and fibrosis, the deletion of ITGB3 alleviates these phenotypes. Additionally, the overexpression of DHHC5 reversed the hallmarks of MASH in ITGB3-deficient mice, confirming the central role of DHHC5 in this process. Mechanistically, ITGB3 is a novel "accelerator" that directly increases CD36-mediated fatty acid uptake by recruiting LYN, then modulating LYN protein stability, and triggering LYN proteasomal degradation. This degradation relieves LYN-mediated inhibition of DHHC5 and promotes ITGB3/DHHC5/CD36 complex formation, thereby enhancing DHHC5-dependent CD36 palmitoylation and subsequent CD36-mediated fatty acid uptake. Pharmacologic inhibition of ITGB3 using cyclic-RGDfk peptide improved serum lipid profiles and hepatic steatosis. This study uncovers a previously unrecognized mechanism by which ITGB3 acts as a driver of hepatic steatosis of hepatic steatosis. Targeted intervention against ITGB3 to modulate CD36-mediated lipid uptake may represent a novel therapeutic strategy for the treatment of MASH.

Aortic dissection (AD), a life-threatening cardiovascular emergency, continues to impose high mortality due to insufficient therapeutic options, as monotherapy targeting angiotensin II type 1 receptor (AT1R) demonstrates limited clinical efficacy. Utilizing single-cell RNA sequencing, we identified integrin β3 as a critical driver of AD progression, with expression levels positively correlated with disease severity. Histopathological validation in human AD specimens and a murine angiotensin II (AngII)-infusion model confirmed marked upregulation of integrin β3 activation. Pharmacological blockade of integrin β3 with Cyclo(-RGDfK) significantly attenuated aortic pathogenesis in vivo , reducing dissection incidence and aortic degeneration. Mechanistically, AngII-mediated AT1R activation induced formation of a receptor complex with integrin β3, triggering its conformational activation. Transcriptomic profiling revealed that activated integrin β3 potentiates vascular endothelial dysfunction by binding glycogen synthase kinase 3β (GSK3β), which stabilizes β-catenin via a non-canonical Wnt signaling axis. This pathway drives endothelial barrier disruption, hallmarks of aortic wall destabilization in AD. Our findings unveil a previously unrecognized synergy between AT1R and integrin β3, implicating aberrant Wnt/β-catenin signaling as a nexus of endothelial injury in AD pathogenesis. These results advocate for a paradigm-shifting dual-therapeutic strategy concurrently targeting AT1R and integrin β3 to restore vascular homeostasis, offering a mechanistically grounded approach to mitigate this lethal disease. This work bridges critical gaps in understanding AD pathophysiology and provides a transformative framework for precision therapeutics. ### Competing Interest Statement The authors have declared no competing interest.

Epilepsy is a serious neurological disorder; however, the effectiveness of current medications is often suboptimal. Recently, stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases, igniting interest in its applicability for epilepsy treatment. This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells. Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells, including genetically modified variants. Clinical trials involving patient-derived mesenchymal stem cells have shown promising results, with reductions in the frequency of epileptic seizures and improvements in neurological, cognitive, and motor functions reported. Another promising therapeutic strategy involves neural stem cells. These cells can be cultured outside the body and directed to differentiate into specific cell types. The transplant of neural stem cells has the potential to replace lost inhibitory interneurons, providing a novel treatment avenue for epilepsy. Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell. In epilepsy treatment, embryonic stem cells can serve three primary functions: neuron regeneration, the maintenance of cellular homeostasis, and restorative activity. One notable strategy involves differentiating embryonic stem cells into γ-aminobutyric acidergic neurons for transplantation into lesion sites. This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy. Induced pluripotent stem cells share the same genetic background as the donor, thereby reducing the risk of immune rejection and addressing ethical concerns. However, research on induced pluripotent stem cell therapy remains in the preclinical stage. Despite the promise of stem cell therapies for epilepsy, several limitations must be addressed. Safety concerns persist, including issues such as tumor formation, and the low survival rate of transplanted cells remains a significant challenge. Additionally, the high cost of these treatments may be prohibitive for some patients. In summary, stem cell therapy shows considerable promise in managing epilepsy, but further research is needed to overcome its existing limitations and enhance its clinical applicability.

Alzheimer’s disease (AD) and ischemic stroke (IS) are prevalent neurological disorders that frequently co-occur in the same individuals. Recent studies have demonstrated that AD and IS share several common risk factors and pathogenic elements, including an overlapping genomic architecture. However, the relationship between IS risk gene polymorphisms and AD has been less extensively studied. We aimed at determining whether IS risk gene polymorphisms were associated with the risk of AD and the severity of AD in AD patients. We utilized data of AD patients and normal controls (NCs) sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. IS risk single nucleotide polymorphisms (SNPs) were identified through the most recent and largest IS genome-wide association study (GWAS) meta-analysis. Subsequently, we conducted SNP-based association analysis of IS-risk SNPs with the risk of AD, along with amyloid, tau, and neuroimaging for AD. The generalized multifactor dimensionality reduction (GMDR) model was used to assess the interactions among IS-risk SNPs and apolipoprotein E (ApoE) ε4. Protein–protein interactions (PPIs) of the IS-risk genes product and APOE were explored using the STRING database. Seven IS-risk SNPs were involved in the study. Five SNPs were found to be associated with at least one measurement of cerebrospinal fluid (CSF) levels of amyloid-beta 1–42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181), as well as the volumes of the hippocampus, whole brain, entorhinal cortex, and mid-temporal regions. After multiple testing corrections, we found that T allele of rs1487504 contributed to an increased risk of AD in non-ApoE ε4 carriers. The combination of rs1487504 and ApoE ε4 emerged as the optimal two-factor model, and its interaction was significantly related to the risk of AD. Additionally, C allele of rs880315 was significantly associated with elevated levels of CSF Aβ42 in AD patients, and A allele of rs10774625 was significantly related to a reduction in the volume of the entorhinal cortex in AD patients. This study found that IS risk SNPs were associated with both the risk of AD and AD major indicators in the ADNI cohort. These findings elucidated the role of IS in AD from a genetic perspective and provided an innovative approach to predict AD through IS-risk SNPs.

Diabetic cardiomyopathy (DbCM) is a chronic metabolic disorder with few effective treatment strategies. Our previous study demonstrated that activated protein C (aPC), a serine protease, exerts cytoprotective effects in DbCM. However, the mechanisms underlying its role in DbCM require further elucidation. We developed a type 1 diabetic mouse model using thrombomodulin gene point mutation mice (TMP/P) with reduced endogenous aPC generation and investigated the protective effects of aPC on DbCM through intraperitoneal injection of protein C (PC). Myocardial functions and structure were assessed by echocardiography and histology. Transcriptomic analysis and immunological evaluation were conducted to investigate the downstream targets. The anti-senescence role of aPC was reaffirmed by PC treatment in vivo and aPC intervention in cultured neonatal rat ventricular myocytes in vitro. Endogenous aPC levels were reduced and positively correlated with cardiac diastolic function in diabetic mice. Cardiomyocytes manifested a senescent phenotype in DbCM. With impaired aPC activation, TMP/P mice exhibited aggravated diabetes-induced cardiac dysfunction and cardiomyocyte senescence. Mechanistically, aPC alleviated cardiomyocyte senescence in DbCM by acting on PAR1/PAR3 receptors to restore the interaction between P85 and CaMKIIδ, thereby inhibiting CaMKIIδ phosphorylation and its nuclear translocation. In summary, our study highlights that aPC ameliorates cardiomyocyte senescence in DbCM via PAR1/PAR3-P85-CaMKIIδ axis.

Background: Early brain injury (EBI) refers to a severe brain injury that occurs within hours to days after sub-arachnoid hemorrhage (SAH). Neuronal damage in EBI is considered a key factor leading to poor prognosis. Currently, our understanding of the mechanisms of neuronal damage, such as neuronal autophagy, is still incomplete. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in metabolism and plays an important role in autophagy. Based on this, this study will further explore the regulation of autophagy by GAPDH after SAH, which may provide a new treatment strategy for improving the prognosis of SAH patients. Methods: The rat SAH model was established by endovascular puncturing, and the trend of autophagy in hip-pocampal neurons at different time points was discussed. Additionally, an in vitro SAH model was created using the oxygenated hemoglobin and hippocampal neuronal HT22 cell line. Through siRNA and overexpression adenovirus techniques, we further investigated the relationship between the key enzyme GAPDH and autophagy in the in vitro SAH model. Results: We observed significant neuronal damage in the hippocampus 24 h after SAH, and the proteomics showed significant enrichment of autophagy-related pathways at this time point. Further studies showed that the expression of LC3 and Beclin1 peaked at 24 h, and the nuclear translocation of GAPDH occurred simultaneously with SAH-induced neuronal autophagy. Our in vitro SAH model confirmed the role of GAPDH in regulating the level of autophagy in HT22 cells. Knockdown of GAPDH significantly reduced the level of autophagy, while overexpression of GAPDH increased the level of autophagy. Conclusion: This study shows the trend of autophagy in hippocampal neurons after SAH, and reveals the regu-latory role of GAPDH in SAH-induced autophagy. However, further studies are needed to reveal the exact mechanism of GAPDH in the nuclear translocation regulation of autophagy and validate in animal models.

自发性脑出血是指非外伤情况下各种原因导致脑血管破裂而引起的脑实质出血,具有高发病率、高致死率、高致残率的特点.针对出血所致原发性脑损伤的治疗效果并不理想,越来越多的研究将重点放在了继发性脑损伤的治疗.脑水肿是脑出血后必然出现的病理生理过程,是最重要的继发性脑损伤之一,与患者预后直接相关.近年来对脑出血后脑水肿的临床前试验提供了许多新的药物治疗潜在靶点,但由于研究设计、样本量等多方面的不足,这些药物尚未有效转化到临床试验中,需要更多大规模、设计严谨的前瞻性临床试验的探索与验证.目前尚无明确改善脑出血预后的脑水肿治疗药物.本文总结了脑出血后脑水肿的病理生理学机制及目前具有转化潜力的治疗脑出血后脑水肿的药物供研究者参考.

Hypertensive intracerebral hemorrhage (HICH) refers to the sudden onset of hemorrhage within cerebral paren-chyma or ventricles of patients with a history of hypertension

Background Glibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH. Methods The Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of >= 3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530). Findings 220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/ 99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%-21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24-1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%-24.1%; P < 0.001). Interpretation Our study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Many fields, including Natural Language Processing (NLP), have recently witnessed the benefit of pre-training with large generic datasets to improve the accuracy of prediction tasks. However, there exist key differences between the longitudinal healthcare data (e.g., claims) and NLP tasks, which make the direct application of NLP pre-training methods to healthcare data inappropriate. In this article, we developed a pre-training scheme for longitudinal healthcare data that leverages the pairing of medical history and a future event. We then conducted systematic evaluations of various methods on ten patient-level prediction tasks encompassing adverse events, misdiagnosis, disease risks, and readmission. In addition to substantially reducing model size, our results show that a universal medical concept embedding pretrained with generic big data as well as carefully designed time decay modeling improves the accuracy of different downstream prediction tasks.

Background: Cerebral fat embolism (CFE) is a subtype of fat embolism syndrome which tends to cause ischemic cerebral infarction. Fat embolism in the cerebral venous system have not been reported. We hereby present a rare case of fat embolus formed in the cerebral venous system 10 days after cosmetic surgery, and describe our management of this patient. Case presentation: A 26-year-old woman with the disturbance of consciousness and recurrent convulsions of the right upper extremity over a 21-h period was admitted to our hospital. The patient was initially diagnosed with haemorrhagic infarction, and cerebral venous thrombosis (CVT) was suspected based on computed tomography (CT). A diagnosis of CFE was confirmed based on surgical findings. Breast and hip augmentation performed 10 days ago was considered the underlying cause. Drug-induced hypothermia, low molecular weight heparin, atorvastatin, dexamethasone, piperacillin/tazobactam, valproic acid, and mannitol were applied. On hospital day 30, she was discharged with a Montreal Cognitive Assessment score of 25. Conclusions: Fat embolism can occur in the cerebral venous system, and may mimic CVT symptoms rather than CFE symptoms. Early identification of the nature of the embolus is essential. The use of heparin may prevent secondary thrombus formation, and accelerate fat embolus decomposition.

Background: The sulfonylurea receptor 1–transient receptor potential melastatin 4 (SUR1–TRPM4) channel is a target key mediator of brain edema. Sulfonylureas (SFUs) are blockers of the SUR1–TRPM4 channel. We made two assessments for the pretreatment of SFUs: (1) whether it associates with lower perihematomal edema (PHE) and (2) whether it associates with improved clinical outcomes in diabetic patients who have acute basal ganglia hemorrhage.Methods: This retrospective case-control study was conducted in diabetic adults receiving regular SFUs before the onset of intracerebral hemorrhage (ICH). All of the patients received the clinical diagnosis of spontaneous basal ganglia hemorrhage. The diagnosis was confirmed by a CT scan within 7 days after hemorrhage. For each case, we selected two matched controls with basal ganglia hemorrhage based on admission time (≤5 years) and age differences (≤5 years), with the same gender and similar hematoma volume. The primary outcome was PHE volume, and the secondary outcomes were relative PHE (rPHE), functional independence according to modified Rankin Scale score and Barthel Index at discharge, and death rate in the hospital.Results: A total of 27 patients (nine cases and 18 matched controls), admitted between January 1, 2009 and October 31, 2018, were included in our study. There was no significant association between SFU patients and non-SFU patients on PHE volumes [15.4 (7.4–50.2 ml) vs. 8.0 (3.1–22.1) ml, p = 0.100]. Compared to non-SFU patients, the SFU patients had significantly lower rPHE [0.8 (0.7–1.3) vs. 1.5 (1.2–1.9), p = 0.006]. After we adjusted the confounding factors, we found that sulfonylureas can significantly reduce both PHE volume (regression coefficient: −13.607, 95% CI: −26.185 to −1.029, p = 0.035) and rPHE (regression coefficient: −0.566, 95% CI: −0.971 to −0.161, p = 0.009). However, we found no significant improvement in clinical outcomes at discharge, in the event of pretreatment of SFUs before the onset of ICH, even after we adjusted the confounding factors.Conclusion: For diabetic patients with acute basal ganglia hemorrhage, pretreatment of sulfonylureas may associate with lower PHE and relative PHE on admission. No significant effect was found on the clinical outcomes when the patients were discharged. Future studies are needed to assess the potential clinical benefits using sulfonylureas for ICH patients.