Citations

ABSTRACT Background and Aims It remains unclear whether different factors influence 30‐ and 90‐day readmission rates. We identified predictors of 90‐day mortality in a global cohort of hospitalised patients with cirrhosis. Methods Variables associated with 30‐ and 90‐day post‐discharge readmission, liver transplantation (LT), and mortality were compared in prospectively enrolled, non‐electively hospitalised adult patients with cirrhosis. Results We enrolled 4208 patients from 125 centres across 37 countries. Alcohol‐related liver disease was the most common aetiology of cirrhosis (40%), followed by hepatitis B virus infection (21%); 47% were readmitted, 8% received liver transplantation (LT), and 23% died within 90 days post‐discharge. In multivariable analysis, country income was significantly associated with both 30‐ and 90‐day readmission rates, the receipt of LT, and mortality within 30 and 90 days post‐discharge (all p ‐values < 0.001). Independent predictors of higher rates of 30‐ and 90‐day readmissions, respectively, were disease severity ( p < 0.001, p = 0.003), prior ascites ( p = 0.025, p = 0.016), prior hospitalisation ( p < 0.001), hyponatremia ( p < 0.001, p = 0.008), and in‐hospital vasopressor use ( p = 0.002, p = 0.011). Prior variceal bleeding independently predicted higher 90‐day readmission rates, whereas age, disease severity, mechanical ventilation, and in‐hospital vasopressor use (all, p < 0.001) increased odds of 30‐ and 90‐day post‐discharge death. Additionally, admission ( p = 0.011) and nosocomial ( p = 0.022) infections increased the odds of 90‐day post‐discharge death. Conclusion In a global cohort of hospitalised patients with cirrhosis, patients in high‐income countries exhibited the highest rates of 30‐ and 90‐day readmission, alongside lower mortality rates and a higher incidence of LT. Variables that predict 30‐day readmission also predicted 90‐day readmission. Understanding these disparities is essential for achieving health equity.

Background: Noninvasive tests are well validated in metabolic dysfunction–associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test–based clinical care pathways for fibrosis risk stratification in MetALD and ALD. Methods: This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013–2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC. Results: Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0–61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD). Conclusions: In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD.

Abstract Technological advancements have increased the number of human spaceflights, including the advent of space tourism and deep space travel. The structure and function of the pulmonary system are gravitationally dependent, highlighting the importance of understanding functional changes within the pulmonary system during transient and sustained microgravity exposure. This systematic review and meta-analysis provide an overview of effects of microgravity (0G) on various functional outcome measures of the human lungs relative to Earth gravity (1G). Twenty-eight studies comprising parabolic flights (~20 seconds), short- (≤30 days) and long-duration spaceflight (>30 days) were assessed. Outcome measures reported in 1G (before flight) and 0G (in-flight) were extracted. Fixed effects models showed microgravity caused a reduction in elastic work and carbon dioxide production, and increases in pulmonary diffusion capacity, compliance, and pulmonary capillary blood volume. Despite this, the effect sizes were small and likely have little clinical significance in healthy individuals. However, they could impact space tourists who have lower health requirements for space travel, and those with underlying obstructive respiratory disorders. The results demonstrate how traditional functional pulmonary testing provides essential physiological benchmarks that complement high-throughput data collection methods, enabling an integrated understanding of how molecular changes translate into functional respiratory outcomes in microgravity.

Importance Clinical trials in cardiovascular medicine aim to deliver high-quality evidence with greater efficiency, including smaller sample sizes and shorter timelines. The selection of sensitive and reliable end points is central to this goal. Right ventricular (RV) structure and function play a critical role in many cardiovascular conditions; however, RV-specific parameters remain underused and inconsistently applied in interventional clinical trials. In this article, the current and emerging role of RV-focused imaging and hemodynamic parameters as end points in clinical trials are explored and a comprehensive framework for their development, validation, and broader implementation is proposed. Observations Across multiple disease domains, RV-focused parameters derived from echocardiography, cardiac magnetic resonance imaging, computed tomography, and right-sided heart catheterization demonstrate potential value in assessing the therapeutic effects of new medicines or devices across a wide range of conditions including heart failure, cardiomyopathies, valve diseases, pulmonary hypertension, and congenital heart conditions. However, their use is inconsistent, and feasibility challenges are common, particularly in multicenter clinical trial settings. Key limitations include variability in imaging acquisition, incomplete data capture, lack of standardized protocols, and insufficient validation linking short-term RV changes to long-term clinical outcomes. Emerging tools such as artificial intelligence may improve reproducibility and efficiency, while collaborative, multidisciplinary efforts are essential for advancing end-point development. Conclusions and Relevance RV-specific end points hold substantial promise for enhancing the sensitivity and mechanistic insight of clinical trials but remain inadequately integrated into current practice. Optimal end-point selection requires balancing clinical relevance, analytical validity, and operational feasibility, with consideration of disease-specific pathophysiology and trial design. Standardization of acquisition, validation of clinically meaningful changes, and centralized data analysis are important next steps. Broader adoption of robust RV metrics supported by technological innovation and cross-sector collaboration has the potential to improve trial efficiency, accelerate therapeutic development, and ultimately enhance patient outcomes.

Background With improved cardiac surgical outcomes, attention has shifted to patient-centred outcomes, including cosmetic appearances of surgical scars. Minimally invasive cardiac surgery (MICS) is often promoted for its cosmetic benefits, yet empirical evidence remains limited. This study aimed to systematically evaluate scar-specific outcomes comparing MICS to conventional full median sternotomy (FMS) in adult cardiac surgery. Methods A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Embase, Central, and Scopus were searched from inception to August 2025. Studies comparing MICS to FMS, reporting scar-related patient-reported outcomes, wound complications, or cosmetic satisfaction, were included. The primary outcome was scar assessment using validated instruments. Random-effects models calculated standardised mean differences (SMD) and risk ratios (RR) with 95% confidence intervals. Results Twenty-two studies comprising 3131 patients (1459 MICS, 1672 FMS) met inclusion criteria. MICS demonstrated significantly better scar assessment scores (SMD −0.74, 95% CI −1.27 to −0.22; p < 0.01; I 2 = 88%, six studies), higher patient satisfaction rates (RR 1.42, 95% CI 1.21–1.66; p < 0.001; I 2 = 84%, 12 studies), and reduced wound complications (RR 0.31, 95% CI 0.20–0.47; p < 0.001; I 2 = 0%, nine studies). Only six studies reported validated scar assessment scores, highlighting limited integration of these measures. Substantial heterogeneity was observed due to diverse assessment tools and surgical techniques. Conclusions MICS can offer significant advantages in scar-specific outcomes compared to FMS in carefully selected patient populations. Cosmetic outcomes should be interpreted within the context of overall effectiveness and may support shared decision making only when clinical outcomes between surgical approaches are comparable. The lack of standardised scar assessment protocols and limited reporting of cosmetic outcomes represent critical gaps. Future research should prioritise standardised scar evaluation tools and expand cosmetic outcome reporting across all cardiac surgical procedures.

Abstract Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p < 1 × 10 −5 ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.