Systemic corticosteroids are administered in acute respiratory distress syndrome (ARDS) for their anti-inflammatory effects. However, the factors that influence their therapeutic efficacy remain poorly understood. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating corticosteroid therapy in adults with non-COVID ARDS. Comprehensive searches of PubMed, CENTRAL, and Web of Science were performed through October 2024. A random-effects model was used to pool the risk ratios (RRs) for short-term all-cause mortality. Inverse-variance-weighted univariable meta-regression analyses were conducted to assess associations between study-level characteristics and treatment effects. Subgroup analysis was performed based on the era of lung-protective ventilation (LPV) adoption using a random-effects model. Adverse events including intensive care unit (ICU)-acquired weakness, superinfection, and barotrauma were also evaluated. The credibility of subgroup effects was evaluated using Instrument for assess the Credibility of Effect Modification Analyses (ICEMAN), and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Eleven RCTs encompassing 1,441 patients met inclusion criteria. Meta-regression identified year of publication as the only potential of effect modifier (coefficient: -0.014; 95
Developmental dysplasia of the hip (DDH), a morphological abnormality of the hip joint, is a well-recognized risk factor for hip osteoarthritis (OA). Much remains unknown about the genetic factors of DDH and its subtypes. To further understand its genetic basis, we conducted genome-wide association studies (GWASs) using a total of 1 085 Japanese DDH cases (including 788 hip dysplasia cases without dislocation and 297 cases with dislocated hip) and 24 000 controls. Additionally, we meta-analyzed with United Kingdom (UK) DDH GWAS and the largest hip OA GWAS to date. We identified three genome-wide significant novel loci, COL11A2, CALN1 and TRPM7, associated with hip dysplasia without dislocation. None of these signals were significant in dislocated hips, and additionally two of the signals had an opposite direction of association, suggesting distinct genetic architectures between the subtypes. The Japanese DDH GWAS identified five associated loci (VEGF-C, FOXC1, SMC2, SLC38A4, and TRPM7), and the trans-ancestry meta-analysis with UK revealed two loci (COL11A1 and GDF5) supported by strong trans-ancestry genetic correlation (r = 1.0). In total, nine loci were identified for DDH and its subtypes, with hip dysplasia without dislocation showing distinct genetic signals from hip dislocation. The meta-analysis of DDH and hip OA identified five novel signals for hip OA. Susceptibility loci and heritability enrichment analyses implicated pathways involving bone formation, collagen type XI trimer, and chondrocyte development, as well as their gene regulation, in DDH. These findings enhance understanding of the genetic architecture and biological pathways underlying DDH, providing new insights into its relationship with OA.
This study investigates the effects of counterface surface texturing on the wear behaviour and particle morphology of ultra-high molecular weight polyethylene (UHMWPE) used in artificial joints. A pin-on-disc wear tester was employed to evaluate four types of polyethylene, including virgin and vitamin E-stabilised variants, with and without gamma-ray irradiation. Surface texturing on Co-28Cr-6Mo alloy counterfaces fabricated using micro slurry-jet erosion (a type of wet blasting technique) reduced the gravimetric wear of polyethylene, particularly in vitamin E-stabilised and gamma-irradiated samples. Textured surfaces facilitated the accumulation of polyethylene transfer films, which occasionally detached to form larger wear particles. However, the effectiveness of this mechanism varied with polyethylene composition. Gamma irradiation enhanced wear resistance through polymer cross-linking but increased material brittleness, limiting its compatibility with textured surfaces. Vitamin E reduced wear through boundary lubrication effects but inhibited transfer film formation, leading to smaller particle sizes in textured conditions. Morphological analysis of wear particles revealed significant differences in particle size, with textured surfaces generating larger particles in most cases. This study highlights the complex interplay between polyethylene properties-such as cross-linking and antioxidant stabilisation-and surface texturing in determining wear performance. These findings underscore the potential of surface texturing to optimise wear resistance and reduce peri-implant osteolysis caused by polyethylene debris. Future work should focus on refining texturing patterns and material properties to enhance the longevity and performance of artificial joint materials.
BACKGROUND AND AIM:Long-term nucleos(t)ide analog (NUC) therapy is essential for chronic hepatitis B (CHB) management. However, data on long-term outcomes, particularly for patients switching to tenofovir alafenamide (TAF) and patients with chronic kidney disease (CKD), remain limited. This study aimed to evaluate the 5-year virological effectiveness and renal safety of sequential TAF therapy, with a focus on those with pre-existing CKD. METHODS:This real-world, multicenter, retrospective study included 414 CHB patients aged ≥ 18 years who switched from a prior NUC to TAF and were followed for at least 5 years. Patients were stratified based on renal function (CKD or non-CKD) at baseline. Study endpoints included 5-year virological efficacy, biochemical and fibrosis responses, and renal function changes. RESULTS:Among the patients, 100 (24.2%) had CKD at the time of switching to TAF. Over 5 years, HBV DNA suppression rate increased from 85.0% to 100%, HBV DNA suppression with target not detected rate rose from 74.0% to 91.0%, and alanine aminotransferase normalization rate (AASLD criteria) improved from 66.0% to 79.0%, similar to the results of patients with non-CKD. Estimated glomerular filtration rate remained stable regardless of baseline renal status or prior NUC regimen, demonstrating long-term renal safety. There were no cases of HBV DNA breakthrough, including among those previously on combination NUCs. For patients with cirrhosis, the FIB-4 index significantly improved over time (p = 0.008). CONCLUSIONS:Sequential TAF therapy demonstrated robust virological efficacy, biochemical and fibrosis improvements, and excellent renal safety over 5 years, irrespective of baseline renal function.
