Stroke survivors experience profound skeletal muscle deterioration, typically losing 15%-20% of skeletal muscle mass in the affected limb within 4-6 months post-stroke. This deterioration accelerates functional decline, falls and secondary sarcopenia. While combined nutrition and exercise interventions have shown synergistic effects in other muscle-wasting conditions, the evidence for stroke remains fragmented. This systematic review and meta-analysis aims to evaluate the efficacy of combined nutrition and exercise interventions on muscle health and performance in patients after stroke.

We will systematically search PubMed, Scopus, Web of Science Core Collection and CNKI from inception without language or date restrictions. Randomised controlled trials evaluating combined structured exercise and nutritional interventions in adults (aged ≥18 years) with stroke will be included. Primary outcomes are muscle strength and muscle mass; secondary outcomes include functional performance, balance, daily living habits, neurological function and muscle composition. Two independent reviewers will conduct screening, data extraction and outcome-level risk-of-bias assessment using the Cochrane Risk of Bias tool for randomised trials. Hierarchical decision rules and robust variance estimation will be applied to address dependent effect sizes arising from multiple time points or concurrent outcome measures. Meta-analyses will be performed using random-effects models, with predefined criteria for switching to narrative synthesis under irreconcilable clinical or statistical heterogeneity. Pre-planned subgroup analyses will explore key moderators (eg, stroke chronicity, baseline nutritional status, exercise modality and supplement type). Certainty of evidence will be graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Ethical approval is not required as this review involves secondary analysis of published data. Findings will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO, CRD420261335163.

Contemporary data show an increasing incidence of venous thromboembolism in children, yet there are few evidence-based treatment guidelines on direct oral anticoagulant use for venous thromboembolism in this population. We aimed to investigate the safety and efficacy of apixaban in paediatric patients with venous thromboembolism.

This prospective, open-label, multicentre, randomised, controlled descriptive study was conducted in 120 sites in 14 countries and included a 12-week main treatment phase followed by an optional 6-12-week extension in the apixaban treatment group for patients who required additional anticoagulation for their index event, were adherent to apixaban administration, and had completed all study visits and activities. Patients were eligible if they were younger than 18 years with an index venous thromboembolism event confirmed by the investigator via imaging and were currently tolerating enteric medications. Exclusion criteria included more than 14 days of standard-of-care anticoagulant treatment before random assignment, active bleeding or a high risk of bleeding, and baseline abnormal liver function or inadequate kidney function. Patients were randomly assigned 2:1 to oral apixaban or standard-of-care (unfractionated heparin, low-molecular-weight heparin, or vitamin K antagonists) per local practice via a central randomisation and drug assignment system (stratified by age). The study used a fixed-dose-by-bodyweight-tier oral apixaban regimen (with nasogastric or gastric feeding, if required). Neonates initiated 0·1 mg oral apixaban twice daily for days 1-7, with the dose remaining at 0·1 mg twice daily thereafter unless otherwise indicated by the results of pharmacokinetics analysis on day 1. For children aged 28 days or older, doses ranged from 0·6 mg twice daily for the first 7 days and 0·3 mg thereafter (4 kg to <5 kg tier) and 10 mg twice daily for the first 7 days and 5 mg twice daily thereafter (highest weight tier, ≥35 kg). The primary efficacy endpoint was a composite of incidence of recurrent venous thromboembolism and venous thromboembolism-related mortality during the main phase (analysed in all randomly assigned patients). The primary safety endpoint was a composite of major bleeding and clinically relevant non-major bleeding during the main phase (analysed in all randomly assigned and treated patients). Efficacy and safety endpoints were adjudicated by an independent committee whose members were masked to treatment assignment. Adverse events were monitored using a combination of solicited and unsolicited event collection. The study is registered with ClinicalTrials.gov (NCT02464969) and is complete.

Between Nov 22, 2015, and April 30, 2024, 229 patients were randomly assigned: 155 to apixaban and 74 to standard of care. Median age was 14·2 years (IQR 6·1-16·5), with 137 (60%) patients age 12 years to younger than 18 years, 44 (19%) age 2 years to younger than 12 years, 32 (14%) age 28 days to younger than 2 years, and 16 (7%) age 27 days or younger. 128 (56%) patients were female, 101 (44%) were male, and 175 (76%) were White. Median treatment duration during the main phase was 83 days (IQR 78-90) in the apixaban group and 83 days (77-86) in the standard-of-care group. The primary efficacy endpoint occurred in four (2·6% [95% CI 0·8-6·7]) of 155 patients assigned to apixaban and two (2·7% [0·2-9·9]) of 74 assigned to standard of care; all events were recurrent venous thromboembolism. The primary safety endpoint occurred in two (1·3% [0·1-5·0]) of 152 apixaban-treated patients and one (1·4% [0·0-8·1]) of 73 standard-of-care-treated patients; all events were clinically relevant non-major bleeding, with no major bleeding events. Rates of any-grade adverse events were numerically similar in the apixaban (131 [86%] of 152 patients) and standard-of-care (61 [84%] of 73]) groups. The most common events were headache (25 [16%] in the apixaban group vs 11 [15%] in the standard-of-care group), epistaxis (24 [16%] vs 14 [19%]), and vomiting (20 [13%] vs four [5%]). There were three treatment-related serious adverse events with apixaban (two [1%] participants with haematochezia and one [1%] with cerebral venous sinus thrombosis) and none with standard of care. There were no treatment-related deaths during the study.

In this descriptive study, the safety and efficacy profile of a fixed-dose-by-bodyweight-tier apixaban regimen was similar to that of standard of care for the treatment of venous thromboembolism and prevention of venous thromboembolism recurrence in children younger than 18 years, providing a potential additional treatment option in this patient population.

Pfizer and Bristol Myers Squibb.

Subarachnoid hemorrhage (SAH) is associated with high mortality and long-term morbidity, as well as a considerable economic burden. Screening for unruptured intracranial aneurysms (UIAs) has the potential to reduce mortality and disability related to SAH, but whether the related costs are justified and provide true health benefits-either in general or specific high-risk populations-remains unclear. Therefore, we conducted a systematic review to determine whether screening of UIAs has been estimated to be cost-effective in any population.

We conducted a literature search in PubMed, Scopus, and Web of Science for studies reporting economic analyses of UIA screening. Eligible studies assessed screening in the general population or in populations with an increased risk of SAH or UIAs. Data were extracted on input parameters, type of model, perspective, and cost-effectiveness outcomes. Study quality was assessed using a modified ECOBIAS checklist.

We included 15 modelling studies from 8 countries, published during 1996-2025. Nine studies evaluated high-risk populations (autosomal dominant polycystic kidney disease, bicuspid aortic valve, coarctation of the aorta, family history, and female smokers), 5 evaluated the general population and 1 examined both. Model input parameters varied widely across studies; assumed UIA prevalence ranged from 0.5% to 19% and annual rupture rates from 0.16% to 12.9%. Twelve studies reported screening as cost-effective (n = 8) or cost-saving (n = 4). All 10 studies evaluating high-risk populations found screening cost-effective. Of 6 studies analyzing screening of general population, 3 concluded it was not cost-effective or was dominated by no screening. All 15 studies were classified as of low quality according to the risk of bias assessment.

Current economic analyses suggest that screening is cost-effective for high-risk populations, whereas evidence for general population remains conflicting. However, the evidence consists exclusively of modelling studies, many with important methodologic limitations. Until prospective data better define SAH risk in screened populations and models more accurately reflect the natural history of aneurysms, the economic analyses of screening should be interpreted with caution. Future research should address these limitations and restrict screening strategies to populations with a demonstrated increase in the incidence of SAH rather than with elevated UIA prevalence alone.

This study aimed to explore the prevalence of these overlapping premorbid geriatric conditions and examine the association between the number of these conditions and the risk of mortality and major cardiovascular events within 1 year after acute stroke.

In this single-centre prospective cohort study, consecutive stroke patients admitted between November 2020 and September 2024 were enrolled. Premorbid frailty was assessed using the 33-item Rockwood Frailty Index. Multimorbidity was defined as the presence of two or more chronic comorbidities other than stroke. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition criteria. Patients were categorised according to the number of overlapping conditions (NOCs), ranging from 0 to 3. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular events within 1 year after admission. Cox proportional hazards regression models adjusted for potential confounders were used to estimate adjusted hazard ratios.

Among 781 patients (mean age 77.9 ± 12.6 years; 390 [49.9%] female), 226 patients (28.9%) were NOC 0, 289 (37.0%) were NOC 1, 161 (20.6%) were NOC 2 and 105 (13.4%) were NOC 3. Compared with NOC 0, the adjusted hazard ratios for the composite outcome were 1.52 (95% CI 0.86-2.68) for NOC 1, 2.64 (95% CI 1.44-4.85) for NOC 2 and 5.20 (95% CI 2.77-9.73) for NOC 3.

One-third of patients with acute stroke had overlapping premorbid geriatric conditions. The NOCs was significantly associated with a composite event in a dose-response manner.

We aimed to develop a machine learning model to predict activities of daily living (ADL) at discharge in stroke patients and identify key predictors to guide rehabilitation decisions.

Data of 589 stroke inpatients (2019-2024) were split into good (BI ≥ 60) and poor (BI < 60) ADL groups. Continuous variables were processed using Z-score normalization, followed by preliminary univariate regression screening (P < 0.05) and final feature selection via LASSO regression (lambda.1se = 0.0488). The screened features were used to train and validate ten machine learning algorithms; 30% of the dataset (n = 177) was allocated as an independent test set for model evaluation, and SHAP analysis was performed to interpret the optimal model.

Six of 41 features were retained. Random forest achieved the best performance (AUC = 0.958; accuracy = 0.936; sensitivity = 0.934; specificity = 0.950). SHAP identified the top drivers: admission Barthel Index, standing balance, Brunnstrom stages (upper and lower limb), dressing, and grooming abilities.

The ADL risk prediction model constructed using machine learning, particularly the random forest model, shows excellent predictive performance and clinical interpretability, making it valuable for individualized risk assessment of daily living skills in stroke patients at discharge.

While maternal congenital heart disease (CHD) is associated with increased risks of adverse pregnancy outcomes, its impact on long-term child development remains unknown. This study aimed to investigate if in-utero exposure to maternal CHD is associated with child developmental vulnerability at school entry.

This population-based cohort study included 256,629 singleton offspring born in British Columbia, Canada between January 1, 1995 and December 31, 2016, with follow up through linkage to teacher-rated Early Development Instrument (EDI) surveys administered in kindergarten around 5-6 years of age. Over 90% children enrolled in participating schools completed the questionnaire. Developmental vulnerability was defined as a score <10th percentile in any two of the five EDI domains: physical health and wellbeing, social competence, emotional maturity, language and cognitive development, and communication and general knowledge. The association between maternal CHD and child developmental vulnerability was examined using modified Poisson regression models, adjusted for maternal age at delivery, parity, country of birth, marital status, neighborhood income quintiles, preexisting psychiatric disorders, and pre-gestational diabetes. A counterfactual four-way decomposition method was used to quantify potential mediation and moderation by preterm birth. Of the 256,629 children (51.4% female) included in the analysis, 456 (0.2%) were exposed to maternal CHD. Developmental vulnerability was identified among 25.2% children exposed to maternal CHD compared with 16.6% among the unexposed. In the adjusted model, maternal CHD was associated with 28% higher risk of developmental vulnerability (aRR 1.28; 95% CI [1.11, 1.48]) compared with no maternal CHD. The increased risk was observed across multiple developmental domains related to physical health and wellbeing (aRR 1.31; 95% CI [1.11, 1.54]), social competence (aRR 1.22; 95% CI [1.02, 1.45]), language and cognitive development (aRR 1.39; 95% CI [1.13, 1.70]), and communication and general knowledge (aRR 1.33; 95% CI [1.09, 1.63]). Preterm birth mediated only about 8% of the overall association. Severe CHD was more strongly associated with developmental vulnerability (aRR 1.98; 95% CI [1.31, 3.00]) compared to mild CHD (aRR 1.19; 95% CI [1.00, 1.42]). However, the study had limited capacity to separate intrauterine effects from potential genetic and postnatal familial influences. Some degree of CHD misclassification is possible, which would likely bias the association toward the null.

In this population-based study, maternal CHD was associated with child developmental vulnerability at school entry. While further research is required to elucidate the mechanisms, enhanced clinical monitoring and tailored support to reproductive age women with CHD may help reduce the risk of developmental vulnerability in their children.

Risk stratification in non-ischemic cardiomyopathies (NICM) remains challenging despite guideline-based phenotypic classification using multimodal diagnostics including endomyocardial biopsy (EMB). We aimed to identify EMB-derived histological and molecular markers that improve phenotypic characterization and long-term risk stratification in patients with NICM.

In this prospective cohort study, 703 consecutive patients with symptomatic NICM underwent standardized multimodal evaluation, including clinical assessment, cardiac imaging, and endomyocardial biopsy. Biopsy specimens were analyzed using histology, immunohistochemistry, and targeted myocardial mRNA profiling. Associations between endomyocardial markers, and fibroinflammatory remodeling, imaging parameters, and molecular signatures were assessed cross-sectionally. Long-term prognostic relevance was evaluated using survival and multivariable prediction analyses during follow-up of up to fifteen years for all-cause mortality, cardiovascular mortality, implantable cardioverter-defibrillator (ICD) implantation, and appropriate ICD discharge.

Elevated myocardial Gremlin-1 expression was associated with increased fibrosis, adverse cardiac remodelling, reduced left ventricular function, and enrichment of pro-fibrotic and inflammatory mRNA signalling pathways. Myocardial and circulating Gremlin-1 expression was independently associated with all-cause and cardiovascular mortality, and ICD implantation and discharge. Machine learning-based phenotyping using histological EMB data identified Gremlin-1 as a key predictive feature of poor prognosis. Incorporation of Gremlin-1 into predictive models significantly improved long-term cardiovascular risk stratification in NICM patients.

Our results unveil that Gremlin-1 is associated with inflammation and cardiac remodelling in patients with NICM, and patients with Gremlin-1⁺ EMB and high plasmatic Gremlin-1 concentrations are at elevated risk to develop adverse cardiovascular events. Thus, the histological evaluation of Gremlin-1 may help to improve risk discrimination and management of NICM and HF patients.

Accidental hypothermia is an unintentional drop in core body temperature below 35 °C. It can occur at any time of year and in any climate, and can affect all age groups. The epidemiology of accidental hypothermia reflects the interaction between biological susceptibility, social conditions and exposure to environmental factors. As core temperature falls and thermoregulation mechanisms become insufficient, the metabolism slows, consciousness deteriorates and the hypothermic myocardium becomes increasingly prone to arrhythmias and cardiac arrest. The prognosis is variable, and treatment outcomes are dependent on multiple factors, with cardiac arrest being the decisive determinant, carrying an in-hospital mortality rate of up to 50%. Diagnosis relies on accurate core temperature measurement whenever possible, together with clinical staging when measurement is unavailable. The management of accidental hypothermia should follow the hypothermic chain of survival: prevent further cooling, handle the patient gently, provide airway, breathing and circulatory support, choose the correct destination hospital, and rewarm the patient using passive, active external, active internal or extracorporeal techniques according to severity. Extracorporeal life support is crucial for patients with hypothermic cardiac arrest. Most survivors of hypothermic cardiac arrest have excellent neurological outcomes. Effective prevention and education, together with well-organized regional pathways of care and personalized strategies to prevent cardiac arrest, are needed to improve outcomes.

The prevalence of carotid atherosclerotic plaque and hyperlipidemia in China is high and continues to rise. Specifically, the incidence of hyperlipidemia among adults is 40.4%, and nearly one-third of asymptomatic adult patients present with carotid plaque; the co-occurrence rate of hyperlipidemia with carotid atherosclerotic plaque is as high as 48%-62%. Although modern medicine has made progress in lipid lowering, plaque stabilization, and surgical intervention, how to leverage the advantages of multi-target comprehensive intervention and simultaneously inhibit the core inflammatory pathways that drive disease progression to reduce high residual risk while improving lipid metabolism through single-target approaches, has become a pressing clinical challenge. In TCM, hyperlipidemia with carotid atherosclerotic plaque falls under the category of vessel impediment and is related to conditions such as &quot;headache&quot; &quot;dizziness&quot;, and &quot;stroke&quot;. Its etiology includes dietary irregularities, emotional disturbances, and constitutional insufficiency. The pathogenesis involves the Qi depression pattern in the early stage, the phlegm-turbidity pattern in the progressive stage, and the dampness-heat pattern in the mid-to-late stage. Regarding treatment strategies, Chaihu-based formulas such as Dachaihu Decoction, Xiaochaihu Decoction, Xiaoyao Powder, Chaihu Shugan Powder, and Chaihu Longgu Muli Decoction are recommended for the Qi depression pattern; Wendan Decoction, Chaichen Zexie Decoction, and Banxia Baizhu Tianma Decoction are suggested for the phlegm-turbidity pattern; Gegen Qinlian Decoction is advised for the dampness-heat pattern. Clinical practice should adhere to the principles of &quot;formula-syndrome correspondence&quot; and &quot;pathogenesis combined with pathology, medicinal nature combined with pharmacology&quot;, with flexible selection and combination of formulas to enhance therapeutic efficacy. Its mechanism of action may be associated with regulating lipid metabolism, inhibiting inflammatory responses, combating oxidative stress, protecting vascular endothelium, and stabilizing plaque structure.

This study aimed to investigate the neuroprotective effects and potential mechanism of Xiaoxuming Decoction(XXM) against cerebral ischemia-reperfusion injury in mice. The middle cerebral artery occlusion/reperfusion model was established in male KM mice using the suture method. The experimental animals were randomly divided into the following groups: sham, model, nimodipine, XXM, Mahuang-Guizhi(MG), and Xiaoxuming Decoction without Mahuang-Guizhi(DXXM). Neurological function deficit scores were assessed using the Zea Longa scoring system. Cerebral infarction rate was measured by 2,3,5-triphenyltetrazolium chloride(TTC) staining. Pathological changes in brain tissue were observed via hematoxylin and eosin(HE) staining and Nissl staining. Non-targeted metabolomics analysis was performed using the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) to explore the potential mechanism. Serum interleukin-1β(IL-1β) and matrix metalloproteinase-2(MMP-2) levels were detected by the enzyme-linked immunosorbent assay(ELISA). Additionally, the expression of tight junction proteins in the blood-brain barrier was detected by Western blot. According to the results, compared with the model group, both XXM and DXXM interventions significantly improved neurological function scores while reducing cerebral infarction rate, neuronal damage, and pathological changes in brain tissue. XXM exhibited a superior protective effect than DXXM did. MG intervention also improved neurological function scores and alleviated pathological damage. Metabolomics analysis revealed 82, 23, and 187 differential metabolites screened from the XXM, MG, and DXXM groups, respectively. The metabolic pathways commonly affected by both XXM and DXXM were purine, alanine, aspartate, and glutamate metabolism, while MG primarily affected the arachidonic acid metabolism pathway. ELISA results showed that XXM and MG significantly reduced IL-1β and MMP-2 levels, while DXXM significantly reduced IL-1β levels. Western blot results indicated that both XXM and DXXM up-regulated the expression of tight junction proteins in the brains of model mice. In conclusion, XXM and DXXM may exert anti-cerebral ischemia-reperfusion injury effects by inhibiting inflammatory factor release, reducing excitatory amino acid toxicity, and enhancing the expression of tight junction proteins in the blood-brain barrier via purine, alanine, aspartate, and glutamate metabolism pathway regulation. XXM exhibited superior effects compared to DXXM. MG may exert neuroprotective effects, to some extent, by regulating arachidonic acid metabolism and reducing pro-inflammatory factor levels.