Dural arteriovenous fistulas (dAVFs) involving the optic nerve sheath are rare and often present subtly. We report a case of a woman in her 50s with a month-long history of left eye redness, swelling and watering. Examination revealed proptosis and chemosis without vision loss or cranial nerve deficits. MRI showed a dilated superior ophthalmic vein (SOV), initially suggesting a carotico-cavernous fistula. However, digital subtraction angiography confirmed a slow-flow intraorbital dAVF supplied by the left ophthalmic and accessory meningeal arteries, draining via the SOV. Conservative management with carotid compression failed, and after 1 year, worsening symptoms and thrombosed venous outflow precluded standard endovascular access. A direct ultrasound-guided SOV puncture was performed using a micropuncture needle. Embolisation with detachable coils and Menox 18 achieved complete fistula occlusion, with clinical improvement. This case highlights the role of catheter angiography in diagnosing intraorbital dAVFs and demonstrates the feasibility of direct SOV puncture when conventional routes are inaccessible.

'Time is brain' is an important concept in ischaemic brain stroke, where expeditious intervention is essential for the preservation of neural tissue. Therapeutic strategies involve the prompt administration of thrombolytic agents and in select circumstances the implementation of mechanical thrombectomy. Central retinal artery occlusion (CRAO) constitutes an ophthalmological emergency and is a form of ischaemic stroke, frequently resulting in profound and irreversible visual impairment. There are currently no universally accepted guidelines delineating the optimal therapeutic time window. In this report, we present the case of a man in his 60s who developed acute, painless monocular vision loss, was rapidly diagnosed with CRAO and subsequently received intravenous tenecteplase and showed near-complete visual recovery within 1 week. This case demonstrates the importance of early interdisciplinary collaboration between ophthalmology and stroke teams and the need for establishment of standardised clinical pathways for the management of CRAO.

Stroke triggers acute vascular and inflammatory mechanisms that predispose the brain to rapid neurodegeneration. Up to 52% of stroke survivors develop cognitive impairment within 6 months and 20% receive a clinical diagnosis of dementia within 5 years. The subacute phase (<6 months) represents a critical window in which the brain may be most responsive to neuroprotective interventions. Multimodal aerobic and resistance training improves cognition in chronic stroke, but whether it improves cognition, neuroimaging markers and blood biomarkers of dementia risk when delivered during this early window remains unknown. The PROTECT trial will compare the effects of 12 weeks of multimodal exercise (moderate-to-high-intensity resistance and aerobic training) versus a low-intensity exercise comparator on cognition, neuroimaging outcomes, blood biomarkers of cognitive decline and dementia risk in people with subacute stroke.

The PROTECT trial is a 12-week, Phase 3, assessor-blinded, multisite Bayesian adaptive randomised controlled trial (RCT) following a two-arm parallel group sequential design with 6-month and 12-month follow-up (NCT07445841). Participants will be randomised to multimodal training or the comparator using concealed allocation with permuted blocks of varying sizes. The primary outcome is cognition, measured using the 13-item Alzheimer's Disease Assessment Scale-Cognitive assessment (ADAS-Cog-13). Secondary outcomes include ADAS-Cog-Plus, structural and perfusion neuroimaging and blood biomarkers of inflammation and neurodegeneration. Tertiary outcomes include cardiorespiratory fitness, functional mobility, muscle strength, body composition, neuropsychological status, patient-reported cognition, quality of life, fatigue and healthcare utilisation. Outcomes will be assessed at baseline, post-intervention (primary endpoint) and at 6-month and 12-month follow-up. Sample size was estimated via 20 000 Monte Carlo simulations using an ADAS-Cog effect size of Cohen's d=0.63 from a previous exercise RCT. The target was ≥80% power to detect this treatment effect at a one-sided type I error rate of 2.5%, using a weakly informative prior centred at zero with a variance of 100. The minimum required was 45 completers per arm (N=90) and accounting for 25% attrition, up to 120 participants (60 per arm) will be enrolled. Pre-planned adaptive features include: (1) two interim analyses at 50% and 75% of completers; (2) early stopping for efficacy and futility; and (3) sample size re-estimation.

Ethical approval to conduct this study has been granted by the Centre de recherche interdisciplinaire en réadaptation du Montréal métropolitain (CRIR MP-50-2025-2294) and Hamilton Integrated Research Board (HIREB 19222). Any protocol amendments will be submitted to the appropriate ethics boards. Written informed consent to participate in this study will be obtained from all participants by study coordinators or assistants. Study results will be published and reported in peer-reviewed journal following Adaptive Designs Consolidated Standards of Reporting Trials extension guidelines.

NCT07445841.

Pregnancy-associated hypertension (PAH) is a prevalent complication during pregnancy. Maternal obesity is a known risk factor for PAH. As nutrition is a key modifiable driver of obesity and metabolic health, this study aimed to evaluate whether early-pregnancy abdominal fat thickness and nutrient intake are associated with the development of PAH.

A prospective cohort study was conducted including pregnant women during 9 to 13+6 weeks of gestation. The abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by ultrasound. Daily intake of key nutrients was assessed using a validated food frequency questionnaire. The primary outcome was development of PAH, encompassing gestational hypertension and pre-eclampsia.

A total of 1912 pregnant women were recruited in this study. The overall incidence of PAH was 7.1% (136/1912). High VAT was associated with a higher PAH incidence than normal VAT (11.2% vs. 4.5%). Independent of BMI, high SAT (≥17.05 mm; adjusted odds ratios (aOR): 2.74, 95% confidence interval (CI): 1.89-3.96) and high VAT (≥28.85 mm; aOR: 2.42, 95% CI: 1.67-3.50) significantly increased risk of PAH. Comparatively, obesity (BMI ≥30 kg/m²) was associated with an aOR of 7.04 (95% CI: 3.94-12.6) for PAH, while the aOR for overweight was 3.16 (95% CI: 2.11-4.71). A predictive model incorporating these adiposity indicators demonstrated an area under the ROC curve of 0.745 (95%CI: 0.703-0.788). In contrast, no significant associations were observed between daily nutrient intake and PAH risk.

In this prospective cohort study, both early-pregnancy SAT and VAT are significant predictors of PAH independent of BMI. The developed predictive model facilitates the early identification of high-risk women, enabling timely interventions to reduce adverse perinatal outcomes.

Vitamin D has been proposed to influence several cardiometabolic risk factors; however, evidence from randomized controlled trials (RCTs) and recent meta-analyses remains inconsistent regarding the magnitude of these effects. This meta-analysis evaluated the effects of vitamin D supplementation on lipid profile, blood pressure, and glycaemic parameters, and explored whether age and baseline serum vitamin D concentrations modified these associations.

A systematic review and meta-analysis of RCTs was conducted to compare oral vitamin D supplementation with placebo in adults. PubMed, the Cochrane Library, and ClinicalTrials.gov were searched systematically. Risk of bias was as-sessed using the Cochrane risk-of-bias tool. Pooled effect sizes with 95% confidence intervals (CIs) were estimated using random-effects models.

A total of 14,051 abstracts were identified, and 45 RCTs were included in the final analysis. Vitamin D supplementation significantly reduced low-density lipoprotein cho-lesterol (LDL-C) by 0.136 mmol/L (95% CI: -0.215, -0.056), systolic blood pressure (SBP) by 2.79 mm Hg (95% CI: -4.65, -0.94), fasting blood glucose (FBG) by 0.11 mmol/L (95% CI: -0.19, -0.04), and hemoglobin A1c (HbA1c) by 0.164% (95% CI: -0.32, -0.01) compared with placebo. Subgroup analyses showed reductions in SBP and LDL-C among participants aged ≥55 years, whereas FBG was reduced in those aged <55 years. While favorable effects on FBG and HbA1c were observed with a baseline blood level of vitamin D of less than 50 nmol/L.

Vitamin D supplementation may modestly improve selected cardiomet-abolic risk factors. Age and baseline vitamin D status may influence these effects, although their clinical sig-nificance remains uncertain. Further well-designed RCTs are needed.

Early identification of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients remains challenging using conventional parameters alone. This retrospective study aimed to assess whether combining left atrial (LA) reservoir strain (εs) with left ventricular (LV) longitudinal strain improves the discrimination of HFpEF among hypertensive patients. We included 50 hypertensive patients with HFpEF (HTN-HFpEF), 56 hypertensive patients without HFpEF, and 50 healthy controls. Cardiac magnetic resonance feature tracking (CMR-FT) was used to measure LV global longitudinal strain (LVGPLS) and strain rates, as well as LA εs, conduit (εe), and booster (εa) strains. Parameters were compared across the three groups. Binary logistic regression was performed to identify predictors of HTN-HFpEF, and receiver operating characteristic (ROC) curves were generated to calculate the area under the curve (AUC). From controls to HTN to HTN-HFpEF, LVGPLS and strain rate showed progressive impairment, while LAVImax and LAVImin progressively increased (all p < 0.001). Compared to the HTN group and healthy controls, the HTN-HFpEF group demonstrated significant impairment in LA functional and strain parameters (all p < 0.001). Binary logistic regression analyses revealed that LVMI, LAVImin, LAεs, and LVGPLS remained independently associated with HFpEF. LAεs alone showed the highest diagnostic performance (AUC = 0.790), and the combination of LAεs and LVGPLS further improved the AUC to 0.841. In conclusion, CMR-FT-derived LA strain demonstrates high discriminative ability for HFpEF in hypertensive patients. The combination of LAεs and LVGPLS offers optimal diagnostic value and may serve as a sensitive non-invasive biomarker for identifying HFpEF in this population.

Autoimmune hypothyroidism (Hashimoto's thyroiditis) is common and has a strong genetic component. Here we performed multi-ancestry genome-wide association meta-analyses encompassing 48,694 Hashimoto's thyroiditis cases, using a precise case definition, and 1,044,134 controls. We identified 155 significant (P < 5 × 10^-8) independent genetic associations, of which 45 variants and 19 loci were not previously associated with hypothyroidism. Six loci were specific for individuals of European ancestry reference populations. Functional enrichment analyses of Hashimoto's thyroiditis-associated genes highlighted immune cells and the spleen, underpinning the importance of T cells in Hashimoto's thyroiditis development. This observation was further supported by 161 significant colocalizations with expression quantitative trait loci in immune cells and 40 in thyroid tissue (for example, TG, VAV3, IRF5), highlighting the interplay between the immune system and the thyroid. Mendelian randomization indicated causal effects of Hashimoto's thyroiditis on cardiovascular traits and expected associations with thyroid hormone levels.

In the osteoarthritic joint, activated macrophages release pro-inflammatory factors that promote cartilage degeneration. The CD200:CD200R immune checkpoint pathway is a promising therapeutic target that inhibits classical macrophage activation. We hypothesized that the presentation of CD200 to macrophages would shift their cytokine profile from pro-inflammatory to pro-regenerative, thereby reducing chondrocyte catabolism. CD200 encapsulated in poly(lactide-co-glycolide) microparticles (MPs) were incubated with murine bone marrow-derived macrophages. CD200 MP treatment reduced protein and gene expression of pro-inflammatory mediators in M1 macrophages and increased protein and gene expression of anti-inflammatory mediators in M2 and M1/2 macrophages. Conditioned media from CD200 MP-treated M1 macrophages reduced the expression of catabolic enzyme genes in chondrocytes. This study is the first to demonstrate that delivery of CD200 alters the inflammatory cascade and paracrine signaling to chondrocytes. There is significant potential for the CD200:CD200R inhibitory signaling pathway to be leveraged as an intra-articular treatment of OA.

Aortic aneurysm and dissection (AA/AD) are life-threatening vascular diseases with high mortality, yet no effective drugs to delay progression. Lipoprotein(a) [Lp(a)] is genetically determined and associated with atherosclerotic disease, but high-quality evidence on its causal role in AA/AD remains limited.

To investigate the association between Lp(a) and AA/AD and assess potential causal relationships with major aortic disease subtypes.

A prospective cohort of 312,332 UK Biobank participants was analyzed. Kaplan-Meier curves, Cox regression, and Fine-Gray competing-risk models assessed associations between Lp(a) and incident AA/AD. Two-sample Mendelian randomization (MR) analyses evaluated the potential causal effects of Lp(a) on AA, abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), and AD.

During a median follow-up of 16.5 years, 3122 AA/AD events occurred. Elevated Lp(a) independently predicted AA/AD with a dose-response relationship (hazard ratio [HR] = 1.40 for >180 vs <50 nmol/L; HR = 1.15 per 75 nmol/L increment). Competing-risk analyses yielded consistent results. MR analyses supported a causal association between Lp(a) and AA (odds ratio [OR] = 1.31, 95% CI: 1.08-1.62) and AAA (OR = 1.80, 95% CI: 1.37-2.37), whereas MR analyses did not provide sufficient evidence for causal associations with TAA or AD.

Lp(a) may serve as a promising biomarker for risk assessment and stratification in aortic disease. However, the MR analysis for AD was limited by low statistical power, and the clinical utility of Lp(a) measurement requires further investigation.