• Identification of clinical phenotypes in Behçet's syndrome using latent class analysis: a step toward precision medicine.
    4 weeks ago
    Behçet's syndrome (BS) is characterised by extreme clinical heterogeneity, underscoring the need for precise patient classification to enable personalised management. While traditional distance-based cluster analysis (CA) has provided new insights, its deterministic approach may not fully capture the complexity of BS. The primary objective of this study was to define BS clinical phenotypes using latent class analysis (LCA), a probabilistic, model-based clustering method that identifies hidden classes based on unobserved patterns. We also aimed to examine sex-related differences in clinical manifestations and treatment requirements across the identified classes.

    We conducted a retrospective, observational, single-centre study including all adult BS patients followed in our department between 2012 and 2022, targeting a sample of 500 patients. LCA was performed using clinically relevant indicators (sex, oral and genital ulcers, skin lesions, articular involvement and major organ involvement). Models were compared based on fit indices, class number, separation, assignment and size. The final model was selected based on both clinical relevance and statistical performance.

    A total of 553 patients (409 males, 144 females) were enrolled, with a mean age of 32±7 years. Five latent classes (C1-C5) with distinct phenotypes were identified. C1 (n=215; 39%), 'vascular type': all patients had vascular lesions, with the highest prevalence of cardiac involvement (12%). C2 (n=171; 31%), 'ocular type': characterised by 100% uveitis and frequent mucocutaneous lesions. C3 (n=40; 7%), 'neurological type': all patients exhibited parenchymal neurological involvement, and 40% had concomitant uveitis. C4 (n=98; 18%), 'skin-mucosa and articular type': marked by 100% oral and genital ulcers, with the highest prevalence of papulopustular lesions (54%) and articular involvement (48%). C5 (n=29; 5%), 'uncertain BS': with 60% uveitis, 48% vascular lesions, and the lowest mucocutaneous involvement. Sex-related clinical differences were observed, with significant male predominance across all major organ classes (C1, C2, C3, and C5), whereas a near-equal sex distribution was noted in the skin-mucosa and articular class (p<0.001). Treatment patterns varied considerably, with higher corticosteroid doses and conventional immunosuppressant use in major organ classes, while biologics were mostly prescribed in the 'ocular class' (C2) and 'uncertain BS' (C5) (p< 0.001).

    This study is the first to apply LCA for BS clinical phenotyping, providing a probabilistic classification that uncovers complex patient subgroups. Five latent classes were identified, with distinct clinical profiles, significant sex disparities, and varying therapeutic needs. These findings are crucial for advancing precision medicine in BS and ultimately improving patient outcomes.
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  • Predictors of post-operative cardiovascular complications for Behçet's disease with pre-operative immunosuppressive therapy.
    4 weeks ago
    Patients with Behçet's disease (BD) with cardiovascular involvement often have more post-operative complications in correcting the pathology by surgical means. This study aims to explore the benefits of pre-operative immunosuppressive therapy, predict complications using inflammatory biomarkers, and evaluate optimal surgery timing.

    This retrospective study analysed predictors of post-operative complications in BD patients who underwent cardiovascular surgery with perioperative immunosuppressive therapy at Guangdong Provincial People's Hospital from 2012 to 2024.

    In-hospital complications were lower in patients who received pre-operative immunosuppressive therapy (9% vs. 58.8%, p<0.001). Rheumatoid factor (RF, hazard ratio [HR] 1.088; 95% confidence interval [CI], 0.998-1.187; p=0.056), platelet-to-lymphocyte ratio (PLR, HR 1.004; 95% CI, 1.000-1.008; p=0.075), and neutrophil-to-lymphocyte ratio (NLR, HR 1.065; 95% CI, 1.002-1.133; p=0.045) were identified as independent risk factors for post-operative complications, while pre-operative immunosuppressive therapy (HR 0.206; 95% CI, 0.061-0.693; p=0.011) was a protective factor. The area under the curve (AUC) for the receiver operating characteristic curve for four or more positive biomarkers was 0.849.

    Pre-operative immunosuppressive therapy is vital for BD patients. Monitoring inflammatory biomarkers helps identify the best timing for surgery and reduces complications.
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  • Specific cardiovascular morphology on computed tomography angiography in patients with right isomerism.
    4 weeks ago
    Children with right isomerism usually accompany complex congenital heart disease, which is associated with pulmonary atresia, common atrioventricular valve, and total anomalous pulmonary venous connection. This study aimed to explore specific cardiovascular morphology associated with right isomerism on computed tomography angiography (CTA).

    We retrospectively reviewed CTA images to assess the atrio-ventricular connections and the spatial relationship between the systemic and pulmonary channels in children with right isomerism.

    We studied 33 patients (17 females). Atrial situs was classified into solitus and inversus in 21 and 12 patients, respectively. Atrioventricular valve morphology included unilateral insertion in 15/33 (46%), balanced insertion into both ventricles in 11/33 (33%), unbalanced insertion into both ventricles in 7/33 (21%), and common atrioventricular valve in 27/33 (82%). The pulmonary connection included atresia and stenosis in 14/33 (42%) and 17/33 (52%), respectively. The anteroposterior relationship between the aorta and the pulmonary trunk was observed in 15/33 (46%). Total anomalous pulmonary venous connection concurred in 21/33 (63%), including supracardiac type in 16/21 (76%) and infracardiac type in 2/21 (10%). Preoperative pulmonary venous obstruction was found in 10/21 (47%). There were 14 patients with bilateral superior caval veins (42%). The anteroposterior relationship between the aorta and the pulmonary trunk was significantly correlated to the pulmonary arterial and venous channel anomalies (p = 0.001 and p = 0.027).

    The spatial relationship between the systemic and pulmonary channels was associated with distinct cardiovascular morphology associated with right isomerism.
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  • Comparative effectiveness of GLP-1 receptor agonists and dual agonists in the treatment of patients with metabolic dysfunction associated steatohepatitis: a systematic review and meta-analysis.
    4 weeks ago
    Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists have been shown to induce histological improvements in patients with metabolic dysfunction-associated steatohepatitis (MASH). However, current clinical evidence on their effectiveness in improving hepatic fibrosis and cardiovascular outcomes remains limited and inconsistent.

    This study synthesized randomized controlled trials (RCTs) from major databases up to August 30, 2025, focusing on patients with biopsy-confirmed MASH. Pooled mean differences were calculated using either a fixed-effects or random-effects model, depending on the degree of heterogeneity observed among the studies.

    Six studies including 1,726 participants were analyzed. Compared with placebo, GLP-1RAs and dual agonists significantly increased the likelihood of histological improvement in MASH without worsening hepatic fibrosis. (OR: 4.51, 95% CI: 3.68 to 5.52). It was associated with a ≥1-stage improvement in hepatic fibrosis without worsening MASH (OR: 1.78; 95% CI: 1.47to2.16). In addition, it contributed to MASH resolution accompanied by a ≥1-stage improvement in hepatic fibrosis (OR: 7.42; 95% CI: 2.98to18.48). In subgroup analyses based on post-treatment weight loss, GLP-1RAs and dual agonists demonstrated significant efficacy in promoting hepatic fibrosis resolution without worsening MASH among patients achieving a ≥10% weight loss (OR: 9.59; 95% CI: 4.01to15.18). However, in patients with <10% weight loss, GLP-1RAs and dual agonists did not demonstrate significant differences (OR: 1.30; 95% CI: 0.92to1.83). Moreover, GLP-1RAs and dual agonists achieved a significant pooled reduction in cardiovascular parameters, including total cholesterol (WMD: -4.15 mmol/L; 95% CI: -13.13 to 4.82) and triglycerides (WMD: -17.70 mmol/L; 95% CI: -21.95 to -13.44). Nevertheless, no significant improvement was observed in Low-Density Lipoprotein Cholesterol (LDL-C) levels (WMD: -0.67 mmol/L; 95% CI: -6.55 to 5.21).

    In patients with MASH who achieve a ≥10% weight loss, GLP-1RAs and dual agonists are associated with significant improvements in hepatic fibrosis, whereas their effect is limited in those with <10% weight loss. However, a significant reduction in LDL-C was observed only among patients achieving substantial (≥10%) weight loss. This finding suggests that for patients requiring comprehensive cardiovascular risk management, additional lipid-lowering strategies may be needed to optimize the effectiveness of the intervention.

    https://www.crd.york.ac.uk/prospero/, identifier CRD42025640318.
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  • Self-Monitoring of Blood Pressure in Yemen: Preliminary Insights Into Knowledge, Attitudes and Practices of Hypertensive Patients.
    4 weeks ago
    Self-monitoring of blood pressure (SMBP) is crucial for managing hypertension (HTN). However, there is a lack of information on the knowledge, attitudes and practices (KAPs) of hypertensive patients regarding SMBP in Yemen. Therefore, this study evaluated these KAPs among hypertensive patients in Yemen.

    A descriptive cross-sectional study was conducted among 598 adult hypertensive patients conveniently sampled from 19 hospitals in five governorates of Yemen (Amran, Dhamar, Sa'dah, Sana'a, and Ibb) in 2023. Data about demographics, HTN, and KAPs regarding SMBP were collected using a structured questionnaire and analyzed using descriptive statistics.

    The response rate was 90.6% (598/660). Of respondents, 30.6% were aware of SMBP, with 72.1% of these practicing it at home. Only 20.2% of patients with perceived awareness knew the optimal timing for BP measurements, and 30% were unaware of any of the precautions SMBP. Although 96.2% of patients believed that SMBP can reduce organ complications, only 39.9% considered it accurate. Of patients aware of SMBP, most (84.2%) endorsed recommending it. Nevertheless, 30.3% of those using SMBP practiced it irregularly, and 53% documented their BP readings, 57.6% shared their home BP readings with physicians, 56.1% compared home and clinic values, and 8.3% reported considering all precautions. Healthcare provider advice (85.6%) and family motivation (75.6%) were the most common reasons for practicing SMBP, followed by owning BP devices (46.2%), while difficulty to operate devices (41.2%), and inability to afford them (35.3%) were the most common reasons for not practicing it.

    Adult hypertensive patients in Yemen show low awareness of SMBP, with notable gaps in understanding proper measurement timing, frequency, and precautions. Doubts about SMBP's accuracy are concerning, yet many express willingness to recommend it, trusting healthcare providers' guidance. Reducing cost barriers and simplifying device use could enhance SMBP adoption, improving HTN management in this vulnerable population.
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  • Neutrophil extracellular traps as therapeutics target in vascular aging.
    4 weeks ago
    Blood vessels are critical in systemic aging with arteries stiffening and calcifying due to chronic inflammation and oxidative stress, driving age-related cardiovascular and cerebrovascular diseases. In this review, neutrophil extracellular traps (NETs) -web-like structures composed of decondensed chromatin, histones, and antimicrobial proteins released by neutrophils-are explored as therapeutic targets in vascular aging. NETs are vital for pathogen defense, but their excessive activation leads to inflammation and vascular pathologies, promoting endothelial dysfunction, inflammatory aging, and vascular remodeling in diseases such as hypertension, atherosclerosis, myocardial infarction, heart failure, atrial fibrillation, ischemic stroke, and Alzheimer's disease. Increasing evidence supports that modulating NETs through inhibitors or scavengers can reduce inflammatory responses, preserve endothelial integrity, and improve prognosis. As a potential therapeutic target, growing attention has been directed toward exploring the balance between NET induction, inhibition, and degradation.
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  • Atherosclerotic cardiovascular disease and mortality in a cohort of patients with rheumatoid arthritis: a prospective study investigating microRNAs as predictors of atherosclerosis and mortality.
    4 weeks ago
    Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) that is not fully explained by traditional risk factors. This study investigated whether a novel microRNA (hsa-miR) panel could improve cardiovascular risk prediction and stratification in RA patients. In this 8-year prospective cohort study, 235 RA patients were enrolled, of whom 148 completed follow-up. We quantified six hsa-miRs (hsa-miR-24, -146, -Let7a, -425, -451, and -155-5p) using qPCR and evaluated their predictive value for two primary endpoints: ASCVD progression (new atherosclerotic plaques and/or non-fatal cardiovascular events) and all-cause mortality using partial least squares discriminant analysis (PLS-DA), linear mixed models, and multivariate regression. During follow-up, 58 patients (39%) experienced ASCVD progression, and 35 died (ASCVD accounting for 31% of deaths). PLS-DA models indicated that baseline hsa-miR levels predicted both ASCVD progression and mortality, explaining 43% and 42% of outcome variability, respectively. Longitudinal changes in five hsa-miRs (-24, -146, -let-7a, -425, and -155-5p) also predicted ASCVD progression. Age, hypertension, and disease duration modulated hsa-miR expression levels over time. This hsa-miR panel represents a promising tool for improving cardiovascular risk prediction in RA, potentially addressing critical gaps in current stratification approaches. Following validation, it could support implementation of personalized cardiovascular risk assessment in RA clinical practice.
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  • Efficacy of adjunctive antidepressants in treating negative symptoms of schizophrenia: a systematic review and network meta-analysis.
    4 weeks ago
    The treatment response for the negative symptoms of schizophrenia is not ideal, and the efficacy of antidepressant treatment remains a matter of considerable controversy. This systematic review and meta-analysis aimed to assess the efficacy of adjunctive antidepressant treatment for negative symptoms of schizophrenia under strict inclusion criteria.

    A systematic literature search (PubMed/Web of Science) was conducted to identify randomized, double-blind, effect-focused trials comparing adjuvant antidepressants with placebo for the treatment of negative symptoms of schizophrenia from database establishment to April 16, 2025. Negative symptoms were examined as the primary outcome. Data were extracted from published research reports, and the overall effect size was calculated using standardized mean differences (SMD).

    A total of 15 articles, involving 655 patients, were included in this review. Mirtazapine (N = 2, n = 48, SMD -1.73, CI -2.60, -0.87) and duloxetine (N = 1, n = 64, SMD -1.19, CI -2.17, -0.21) showed significantly better efficacy for negative symptoms compared to placebo. In direct comparisons between antidepressants, mirtazapine showed significant differences compared to reboxetine, escitalopram, and bupropion, but there were no significant differences between other antidepressants or between antidepressants and placebo. No publication bias for the prevalence of this condition was observed.

    These findings suggest that adjunctive use of mirtazapine and duloxetine can effectively improve the negative symptoms of schizophrenia in patients who are stably receiving antipsychotic treatment. Therefore, incorporating antidepressants into future treatment plans for negative symptoms of schizophrenia is a promising strategy that warrants further exploration.
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  • Healing Right Way: A Stepped Wedge Cluster Randomised Controlled Trial Aiming to Enhance Quality of Life for Aboriginal Australian Survivors of Stroke and Traumatic Brain Injury.
    4 weeks ago
    To determine the effect of cultural security training (CST) for health professionals and access to an Aboriginal Brain Injury Coordinator (ABIC) for Aboriginal Australians with stroke or traumatic brain injury (TBI).

    A stepped wedge cluster randomised controlled trial; the intervention package consisted of CST for hospital professionals and 6-month access to ABICs providing education, support, liaison and advocacy; the commencement order of the intervention phase was randomised.

    Four urban and four rural hospitals in Western Australia, 2018-2022.

    Aboriginal adults ≥ 18 years hospitalised with stroke or TBI.

    Primary outcome was quality of life (Euro QOL-5D-3L Visual Analogue Scale (EQ-VAS)) score at 26 weeks post-injury. Secondary outcomes were modified Rankin Scale, Functional Independence Measure, Hospital Anxiety and Depression Scale, Modified Caregiver Strain Index at 12 and 26 weeks, rehabilitation occasions of service, hospital compliance with minimum processes of care (MPC), acceptability of interventions, feasibility of ABIC role and costs.

    In total, 108 participants recruited (target 312), 75% rural residents; 26-week outcomes assessment completed for 78% of participants. The adjusted mean QoL showed no significant difference (p = 0.83). The MPC outcome favored the intervention group, adjusted difference in means 6.8% at 26 weeks, 95% CI (0.40%, 13.26%). There were no significant differences between control and intervention groups for other secondary outcomes.

    CST and implementation of an ABIC were feasible, acceptable and improved care processes for a predominantly rural population. Health outcomes did not differ. The effects of the COVID-19 context are discussed.

    ACTRN12618000139279.
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  • Impact of Pre-Heart Transplant Levosimendan Administration on Post-Transplant Vasoplegia and Primary Graft Dysfunction.
    4 weeks ago
    Levosimendan, a calcium-sensitizing inotropic agent, is used in patients with advanced heart failure (HF) awaiting heart transplantation (HT). Its prolonged effects, due to an active metabolite, may influence post-transplant vasodilation, particularly when administered shortly before HT. However, its impact on post-HT complications such as vasoplegia and primary graft dysfunction (PGD) remains unclear. This study aimed to evaluate whether preoperative levosimendan affects these outcomes.

    This retrospective, multicenter observational study included adult HT recipients from 2010 to 2022 across three Spanish centers. Patients were grouped based on whether they received levosimendan within 1 month prior to HT. Main outcomes were post-HT vasoplegia (defined as cardiac index ≥2.5 L/min/m2, systemic vascular resistance <1000 dyn·s·cm-5, and either a vasoactive-inotropic score (VIS) > 20 or norepinephrine administration >0.1 µg/kg/min at 24 h post-HT) and severe PGD, as defined by the 2014 ISHLT criteria. Secondary outcomes included all-cause mortality. Subgroup analyses were performed for patients receiving levosimendan within 1 week of HT and by sex. Statistical analyses included propensity score (PS) matching, Kaplan-Meier curves, and multivariate Cox regression models.

    Among 598 HT recipients, 94 (15.7%) received levosimendan preoperatively. After PS adjustment, no significant differences were found in the incidence of vasoplegia (40.0% vs. 39.2%, OR 0.99, p = 0.98) or severe PGD (10.6% vs. 10.3%, OR 1.25, p = 0.63) between groups. Post-HT mortality was also not different (HR 0.78, p = 0.37). Vasoplegia did not affect mortality, while severe PGD was linked to higher mortality. Subgroup and sex-based analyses revealed no significant outcome differences.

    Pre-HT levosimendan use was not associated with increased early post-transplant complications and appears to be a safe strategy.

    This study evaluated whether giving levosimendan before HT affects early post-transplant complications. Among 598 patients, 94 received levosimendan within a month before surgery. Results showed no significant differences in rates of vasoplegia, severe primary graft dysfunction, or mortality. Levosimendan use appears safe in the immediate pre-transplant setting.
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