Hypertension and dyslipidaemia are key modifiable risk factors of dementia, and the combined use of statins and antihypertensive medications (AHMs) may offer protective benefits. However, evidence on specific combinations remains limited. This study examined associations between dementia risk and the use of statins with angiotensin-II (Ang-II) promoting AHMs (drugs that increase Ang-II formation) compared with statins combined with Ang-II suppressing AHMs (drugs that decrease Ang-II formation).

This was a prospective study using data from the 45 and Up Study cohort, a large population-based cohort in New South Wales, Australia. Participants aged ≥ 45 years with hypertension and dyslipidaemia were included if they had concurrent statin and AHM use. Exposure groups were defined as either users of statins and Ang-II promoting AHMs (angiotensin II receptor blockers [ARBs], thiazides, and dihydropyridine calcium channel blockers [DHP CCBs]) or statins and Ang-II suppressing AHMs (angiotensin-converting enzyme inhibitors [ACEIs], beta-blockers [BBs], and non-DHP CCBs). Medication exposure was determined based on a proportion of days covered (PDC ≥ 80%). Baseline characteristics of the two groups were balanced using 1:1 pair propensity score matching. The Cox proportional hazards model was used to estimate hazard ratios (HRs) adjusted for diet, physical activity, comorbidities, and concomitant medications.

Among 34,610 matched participants (17,305 per group; a mean age [standard deviation (SD)] of 65.8 (8.8) years; a mean follow-up (SD) of 12.4 (5.1) years), use of a statin plus Ang-II promoting AHM was associated with a 12% lower dementia risk (HR, 0.88; 95% CI, 0.79-0.98) and 13% lower all-cause mortality (HR, 0.87; 95% CI, 0.82-0.93) compared to statin plus Ang-II suppressing AHM combinations. Combinations of rosuvastatin or atorvastatin with Ang-II promoting AHMs (HR, 0.43; 95% CI, 0.36-0.50 and HR, 0.74; 95% CI, 0.64-0.84, respectively) conferred greater benefit compared with simvastatin combined with Ang-II promoting AHMs. The effects were consistent across both sexes, with the protective association observed only in the 65-74-year age group, and combinations involving ARBs demonstrated superior benefit compared to those with ACEIs. Findings were robust across sensitivity analyses, including applying a competing-risks model for death.

Combined therapy with a statin plus Ang-II promoting AHMs, particularly rosuvastatin or atorvastatin with an ARB, was associated with lower dementia risk, suggesting cognitive benefits may inform therapy selection. Future randomised trials should confirm these findings and explore underlying mechanisms.

Hemiplegic shoulder pain (HSP) is a major cause of disability that is still challenging to manage in clinical practices. Both pulsed radiofrequency (PRF) and repetitive transcranial magnetic stimulation (rTMS) could reduce poststroke HSP to certain extents. However, it remains unknown whether combined PRF and rTMS treatment could increase analgesic efficacy for poststroke HSP.

To evaluate the therapeutic efficacy of combined PRF and transcranial magnetic stimulation in treating HSP.

This was a randomized, assessor-blinded pilot study.

The rehabilitation department of a single hospital.

In this pilot study, a 3-arm study design was utilized to compare the treatment efficacy of combined PRF and rTMS treatment with a single PRF or rTMS strategy. Patients were randomly assigned to receive PRF, rTMS, or combined treatment. Outcomes assessments included pain intensity, motor activity, and neurophysiological activities.

Our data indicated that rTMS acted more efficiently to reduce pain than PRF treatment. Combined treatment had a larger long-term efficacy than rTMS treatment alone. Both combined and single treatment improved motor recovery and neural transmissions, such as suprascapular nerve amplitude and somatosensory N20.

As we designed a pilot study, the sample size was small in each treatment arm. Our findings thus need to be validated in future large studies.

These novel findings provide a safe and effective treatment strategy for poststroke HSP by combining PRF with rTMS treatment.

Chinese Clinical Trial Registry: ChiCTR2500100181.

Chronic post-stroke aphasia is heterogeneous, and focal lesion models do not fully explain persistent language impairment. We tested whether accelerated brain aging and regional white matter hyperintensity (WMH) burden provide complementary MRI markers of residual brain vulnerability in chronic post-stroke aphasia.

We analyzed Western Aphasia Battery Aphasia Quotient (WAB-AQ), brain-predicted age difference (Brain-PAD), aphasia subtype, fluency phenotype, regional WMH burden, and lesion-volume/site measures in 137 participants from the Aphasia Recovery Cohort using covariate-adjusted regression, mixed-effects modeling, lesion-aware sensitivity analyses, and internal validation.

Higher Brain-PAD was associated with lower WAB-AQ in the full cohort (β = -3.38, p < 0.001) and remained significant after accounting for subtype and fluency structure. Non-fluent participants had higher Brain-PAD than fluent participants (β = 2.19, p < 0.001). Among candidate WMH measures, anterior WMH was the most consistently supported vascular feature. In the final WMH-complete model, Brain-PAD (β = -3.11, p < 0.001) and anterior WMH burden (β = -8.20, p = 0.001) were independently associated with lower WAB-AQ and improved model fit beyond Brain-PAD alone (ΔR² = 0.077). In lesion-aware sensitivity analyses, total lesion volume was strongly associated with WAB-AQ, but Brain-PAD and anterior WMH remained associated with WAB-AQ after lesion-volume adjustment.

Chronic post-stroke aphasia severity was better characterized by a lesion-aware dual-vulnerability model in which accelerated brain aging indexed global structural vulnerability and anterior WMH burden captured complementary lobar vascular white matter injury beyond total lesion volume.

This multicenter retrospective study aimed to describe temporal trends in clinical indications for plasma exchange (PE) in adult patients at four quaternary-care hospitals in Bogotá (2008-2024) and to examine their distribution across successive ASFA guideline editions. Adults ≥ 18 years who received ≥ 1 PE session were included; indications were coded using ICD-10, and outcomes were classified as complete improvement, partial improvement, no change, or death. Descriptive statistics were performed using RStudio. Of 970 patients screened, 758 met eligibility criteria. Median age was 47 years (IQR 33-60); 62.4% were women. Neurological and rheumatological indications predominated (n = 634, 83.6%), particularly neuromyelitis optica spectrum disorders and ANCA-associated vasculitis. A total of 3954 sessions were performed (median: 5 per patient; IQR: 5-6). Hypocalcemia was the most frequent complication. Overall, 74.0% achieved complete or partial improvement, with higher rates in neurological conditions. Sixty-nine deaths occurred (9.1%), mostly attributed to systemic autoimmune diseases. Over the study period, neuroimmunological indications increased markedly, while use of PE for ANCA-associated vasculitis declined following its reclassification to ASFA category III in 2023. ASFA categories I and II accounted for 92.7% of indications; Category I representation declined from 66.7% (2008-2010) to 40.6% (2023-2024), while case volume grew from 21 to 266 patients per triennium. Over 16 years, PE indications shifted substantially toward immune-mediated neurological disorders, driven by expanded diagnostic availability for AQP4-IgG and MOG-IgG and evolving ASFA recommendations. These findings underscore the need for prospective studies and a national PE registry in Colombia.

Inpatient care for venous leg ulcers is often inconsistent, with delays in vascular assessment and compression therapy contributing to prolonged healing and fragmented treatment. This evaluation examined a front-door Tissue Viability Nurse-led service providing specialist assessment at hospital admission. A descriptive service improvement evaluation was conducted. From 2022, patients in the Assessment Ward admitted with leg wounds received Tissue Viability assessment within one working day, including Doppler-based vascular evaluation, wound bed preparation, peri-wound skin optimisation and early initiation of compression therapy. Compression bandaging became a core clinical skill for registered nurses, supported by a rationalised product formulary. This observational evaluation and qualitative review suggested that early specialist involvement supported the timely initiation of compression therapy, reduced variation in inpatient wound care and minimised duplicate referrals through clear Tissue Viability-led care plans. Staff confidence in applying compression was perceived to improve, collaboration with vascular, dermatology and community services strengthened and patients informally reported clearer information and greater continuity of care, supporting a timelier approach to care delivery. Positioning Tissue Viability expertise at the Assessment Ward appeared to support improvements in the consistency and safety of care processes in leg ulcer management. This front-door specialist model, rarely described in acute care literature, enhanced timeliness and coordination and provides a scalable approach to addressing international gaps in acute wound care pathways.

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.