Hyperleptinaemia is an emerging mechanism involved in the pathogenesis of obesity-related primary hypertension (HTN). This substudy from a large clinical trial aimed to determine differences in [leptin] in physically inactive adults (n = 69, 46.4% women) with HTN and living with overweight or obesity following a 16-week supervised aerobic exercise training (EX group, 2 days/week) intervention with an attention control (AC, only physical advice) group, both combined with a hypocaloric diet; to analyse whether the changes observed after the intervention were maintained after 6 months (6M); and to explore differences and potential mechanisms affected by sex. Cardiorespiratory fitness and body composition evaluation, and biochemical measurements were conducted. After the intervention [leptin] decreased in both groups (EX, 36%, p = 0.003; AC, 23%, p = 0.06), returning to baseline concentrations after 6M of follow-up in both groups. Changes over time were similar in both sexes, with no significant time × group interaction (p > 0.05). For all participants, body mass index was the only factor independently associated with [leptin] (β = 0.339, B = 2.11, SE = 0.53), explaining 12% of the variability (p < 0.001). Among women, waist-to-hip ratio (12%, β = 0.365, B = 135.8, SE = 59.4) and fat-free mass (11%, β = -0.443, B = -2.33, SE = -2.27) additionally and independently explained leptin variability (p < 0.05). A hypocaloric diet combined with supervised exercise appears to be an effective strategy for regulating [leptin] and improving metabolic health in individuals with HTN and overweight or obesity. The influence of fat distribution on leptin dynamics in women calls for research to consider sexual dimorphism.

Ischemic stroke poses a significant global health burden. Accurately identifying symptomatic carotid atherosclerotic plaques, beyond relying solely on stenosis degree, remains a critical challenge for precise stroke risk stratification. We aimed to develop and validate a deep learning radiomics (DLR) signature based on multicontrast MRI to identify symptomatic carotid plaques accurately.

In this retrospective multicenter study, 409 carotid arteries from 355 patients with carotid atherosclerosis were enrolled (219 training, 95 internal validation, 95 external test). Deep learning (DL) and radiomics features were extracted and combined from automatically segmented plaque regions on multicontrast MRI. The optimized DLR signature derived from a 3-stage feature selection pipeline was leveraged to train diverse machine learning classifiers for robust identification of symptomatic carotid plaques. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC) and compared against clinical models, radiomics-only models, and DL-only models. Subgroup analysis across stenosis severities and comparison of MRI-based American Heart Association lesion types between DLR-defined risk groups were performed.

The DLR model with logistic regression demonstrated excellent performance in identifying symptomatic plaques, achieving AUROCs of 0.975 (95% CI, 0.954-0.992), 0.933 (95% CI, 0.876-0.976), and 0.881 (95% CI, 0.807-0.939) in the training, internal validation, and external validation cohorts, respectively. It significantly outperformed the clinical model (AUROCs of 0.701, 0.749, 0.711; P < .05), radiomics-only model (AUROCs of 0.877, 0.839, 0.789; P < .05), and DL-only model (AUROCs of 0.948, 0.894, 0.845; P < .05 in training/external). Performance remained consistently high across stenosis severity subgroups (AUROCs of 0.895-0.982 for severe, 0.863-0.971 for mild-moderate stenosis). DLR-defined symptomatic groups showed significantly higher prevalence of complex type VI lesions (internal: 50.0% versus 14.8%, P < .001; external: 48.7% versus 20.7%, P = .004) and lower prevalence of predominantly calcified type VII lesions (external: 8.1% versus 43.1%, P < .001) compared with asymptomatic groups.

The developed multicontrast MRI-based DLR signature provides a highly accurate and robust tool for the automated identification of symptomatic carotid plaques, underscoring its potential value as a noninvasive tool to guide personalized stroke prevention strategies.

To determine the correlation between weight-adjusted-waist index (WWI) with prehypertension and hypertension in the general population. This cross-sectional study was conducted from September 13, 2023 to November 30, 2023 and included 4885 permanent residents in Zhejiang Province. The association between WWI with prehypertension and hypertension was carefully evaluated using logistic regression models and penalized spline functions. The category-free analysis was performed to corroborate whether WWI enhanced the ability to estimate prehypertension and hypertension. Multivariable logistic regression indicated that after adjustment for conventional risk factors, each standard deviation increase in WWI levels was associated with a 29% and 50% increased risk of prehypertension (hazard ratio, 1.29; 95% confidence interval, 1.14-1.45) and hypertension (1.50; 1.34-1.68), respectively. Referring to the participants in the lowest quartile of WWI, those in the highest quartile had a significantly increased risk of prehypertension (1.64; 1.17-2.30) and hypertension (2.47; 1.80-3.39). Smoothing curve fitting and trend logistic regression suggested a linear positive correlation, and the robustness of these findings was observed in interaction tests and subgroup analyses. The category-free analysis suggested that adding WWI levels to the traditional model ultimately improved the predictive ability of prehypertension and hypertension. The results of this study confirmed the significant correlation between WWI with prehypertension and hypertension, independent of conventional risk factors. More importantly, these findings suggested the potential usefulness of WWI levels to improve the risk stratification of hypertension and prehypertension.

This boy in mid childhood presented with a sudden, excruciating occipital headache following a week of progressive gait unsteadiness and neck-accentuated meningeal pain. CT demonstrated tetraventricular haemorrhage with early obstructive hydrocephalus and perimesencephalic subarachnoid blood. CT angiography/magnetic resonance angiography (MRA) and digital subtraction angiography revealed a cervicomedullary perimedullary arteriovenous fistula (PMAVF) supplied by the anterior and posterior spinal arteries with a single venous pouch aneurysm at C3-4. Emergency external ventricular drain (EVD) placement was performed. Definitive endovascular cure was achieved 72 hours later using simultaneous bilateral micro-catheterisation of the venous pouch and 'parallel' coiling under multimodality neuromonitoring, completely occluding the shunt while preserving spinal arterial flow. The patient recovered without any neurological deficit, the EVD was gradually weaned over the first 5 postoperative days and removed without clinical or radiological difficulty, and the 12-week MRI/MRA confirmed complete occlusion; at that time, he had returned fully to school and sports including football. This case highlights the importance of cervicomedullary vascular imaging in atraumatic paediatric Subarachnoid Hemorrhage (SAH)/intraventricular haemorrhage and illustrates that complex type III/C PMAVFs can be safely cured in a single session using a dual-pedicle coiling strategy in select cases.

Despite advances in acute treatment, stroke remains the first cause of acquired disability. Today, there is no effective pharmacological therapy to improve recovery beyond the acute phase. Preclinical studies suggest that inhibition of the C-C chemokine Receptor 5 (CCR5) may promote recovery by enhancing plasticity in the peri-infarct cortex. However, the role of CCR5 to improve outcome after ischaemic stroke in humans is unknown.

MAraviroc for STrokE Recovery is a phase II, single-centre, randomised, double-blind, placebo-controlled trial. The aim is to assess the efficacy and safety of the CCR5 antagonist Maraviroc for improving motor recovery of the upper limb after ischaemic stroke. 80 ischaemic stroke patients with moderate but incomplete upper extremity motor impairment will be enrolled within 7 days of onset. Participants will be randomised (1:1) to receive either oral maraviroc (300 mg two times per day) or placebo for 90 days in addition to standard rehabilitation therapy. The primary outcome is upper limb motor function assessed using the Fugl-Meyer Assessment for the Upper Extremity at day 90. Secondary outcomes include motor learning skills and plasticity in the peri-infarct region assessed using MRI connectivity and spectroscopy at 90 days.

The study protocol has been reviewed and approved by the Geneva Competent Ethics Committee (Commission Cantonale d'Éthique, CEC; Reference Number: CCER 2024-02359) and Swissmedic (Swiss Agency for Therapeutic Products). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed publications and scientific conferences.

2024-02359; NCT07080567.

To characterise post-stroke depression (PSD) diagnostic and treatment patterns in an outpatient primary care setting, including timing, screening methods, therapeutic interventions and associations with mortality.

A retrospective cohort study.

Maccabi Healthcare Services, the second largest Healthcare Maintenance Organisation in Israel, covering more than 2.7 million citizens between 2016 and 2022.

Participants were adult patients with a new stroke diagnosis between 2016 and 2022 and a subsequent diagnosis of depression according to International Classification of Diseases clinical criteria or antidepressant medication initiation. Patients with a diagnosis of depression or antidepressant treatment prior to stroke were excluded from the study.

Primary outcomes included PSD diagnosis rates, time to diagnosis and treatment, use of screening questionnaires, specialty of the physician making the diagnosis and all-cause mortality. Secondary outcomes included referral rates to mental health services, rehabilitation participation and its impact on mortality.

Among 11 499 patients, PSD occurred in 4620 (40.2%) patients. Primary care physicians diagnosed 53.1% of cases based on clinical assessment; only 4.5% of patients underwent Patient Health Questionnaire-2 screening. Most diagnoses occurred in the first year (53.4%). Antidepressants, predominantly selective serotonin reuptake inhibitors (58.3%), were initiated within 30 days in 65.1% of diagnosed patients. Patients with PSD demonstrated higher rehabilitation participation (69.5% vs 48.5%, p<0.001) and paradoxically lower mortality rates (22.1% vs 27.9%, p<0.001). Patients without PSD were older with a greater comorbidity burden. Cox regression identified physiotherapy visits (HR=0.625, p<0.001) and mental health consultations (HR=0.642, p<0.001) as protective factors.

In this cohort, in an outpatient primary care setting, primary care physicians diagnosed the majority of PSD cases, predominantly relying on clinical criteria, without using screening tools. The majority of PSD diagnoses occurred during the first year after stroke (53.1%), suggesting that repeated evaluation might be appropriate during this follow-up period. Early antidepressant treatment and enhanced rehabilitation engagement may positively influence mortality outcomes in patients with PSD. Low utilisation of standard screening tools and mental health referrals represents an area for potential improvement in PSD management.

Heart failure occasionally develops after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), despite procedural success. Most cases present with mildly reduced or preserved left ventricular ejection fraction (LVEF), underscoring the role of diastolic dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown benefits across the heart failure spectrum, independent of LVEF. The purpose of this randomised controlled trial is to determine whether adding a SGLT2 inhibitor to conventional medications improves LV diastolic function in patients with preserved LVEF after TAVI.

This study is a prospective, single-centre, open-label, randomised, parallel-group, two-arm trial enrolling patients with mildly reduced or preserved LVEF (≥40%) undergoing TAVI for severe AS. Participants will be randomised in a 1:1 ratio to receive either conventional medications plus empagliflozin or conventional medications alone. In the empagliflozin group, participants will receive conventional medical therapy plus empagliflozin 10 mg orally once daily, initiated 4 weeks after TAVI. Empagliflozin treatment will continue throughout the study period. Participants in the control group will receive conventional medications without empagliflozin. The primary endpoint is the change in E/e', assessed by echocardiography from treatment initiation at 4 weeks post TAVI (day 1) to day 168 (week 24). Each group will include 50 patients, totalling 100 patients.

Ethical approval for this study has been obtained from the Chiba University Hospital Certified Clinical Research Review Board (CRB0111-25).

jRCT1031250190.

Overweight and obesity are major global public health challenges and increase the risk of type 2 diabetes, dyslipidaemia, hypertension and cardiovascular disease. Exercise is a safe and cost-effective non-pharmacological strategy to improve cardiometabolic health, yet the optimal combinations of exercise modality and dose for key cardiometabolic outcomes remain uncertain. This protocol aims to synthesise evidence on the joint effects of exercise modality and dose in adults with overweight or obesity and to identify modality-dose combinations associated with the most favourable cardiometabolic profiles.

We will search PubMed, Embase, Web of Science, the Cochrane Library, Scopus, SPORTDiscus and China National Knowledge Infrastructure (CNKI) from inception to June 2026 for randomised controlled trials of exercise interventions in adults (≥18 years) with overweight or obesity. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. We will conduct a Bayesian model-based dose-response network meta-analysis to estimate modality-specific dose-response relationships across cardiometabolic outcomes, with exercise dose standardised as metabolic equivalent of task minutes per week. Non-linear dose-response curves will be fitted to estimate minimum effective doses and optimal dose ranges. Meta-classification and regression tree analyses will be used to explore potential effect modifiers.

Ethical approval is not required because no primary data will be collected. Findings will be submitted to a peer-reviewed journal.

CRD420251229131.

Surgical and endovascular procedures are established treatments for extracranial stenoses of the internal carotid artery (ICA) according to current guidelines. Revascularization is generally recommended for symptomatic ICA stenoses between 50% and 99%. For asymptomatic stenoses, optimal medical therapy is the primary focus; revascularization should be considered for stenoses between 60% and 99%, depending on the individual risk. The choice between endarterectomy (CEA) and carotid artery stent implantation (CAS) is made by an interdisciplinary team, considering patient- and anatomy-specific factors. Interventional therapy is well-established; however, studies show an increased incidence of minor strokes and transient ischemic attacks (TIAs), which is why patient selection and embolic protection are becoming increasingly important in the field of endovascular revascularization. Technological advancements, such as innovative double-layer stents for improved plaque coverage, increase the safety of the procedure, and reduce the peri-procedural stroke rate. Anatomical features are essential for successful treatment when selecting devices and planning procedures.

Invasive treatment of carotid stenosis is directed towards the prevention of ischemic stroke. Contemporary guidelines, based on the best available evidence, recommend carotid endarterectomy for symptomatic carotid stenosis of 50-99%. Revascularization should ideally be performed within 48 hours to 14 days following the index ischemic event. In asymptomatic patients, intervention is indicated in the presence of clinical or morphological markers associated with an increased risk of carotid stenosis-related stroke. Carotid artery stenting represents a complementary alternative to endarterectomy, particularly in patients at high surgical risk. Given that several recommendations are based on expert opinion rather than high-level evidence, interdisciplinary decision-making plays a crucial role. Patients with limited life expectancy should not undergo invasive treatment; all patients with carotid artery disease should receive optimal medical therapy.