Citations

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.

Patients in the liso-cel plus ibrutinib cohort of the phase 1/2, open-label TRANSCEND CLL 004 study had relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and received liso-cel (50×106 [dose level (DL)1] or 100×106 [DL2] chimeric antigen receptor-positive T cells) with concurrent ibrutinib from enrollment through 90 days after liso-cel infusion or longer per investigator discretion. Primary end point was complete response/remission (CR)/CR with incomplete marrow recovery (CRi) by investigator assessment. Among 56 patients who received ibrutinib plus liso-cel (DL1, n=5; DL2, n=51), median (range) age was 64.5 years (44‒77), 98% had high-risk cytogenetics, 55% had progression on Bruton tyrosine kinase inhibitor and venetoclax failure, and median (range) number of prior therapies was 5 (1‒13). Median (range) follow-up was 24.8 months (3.1‒51.8). At DL2, CR/CRi rate was 45% (95% confidence interval [CI], 31‒60) and overall response rate was 86% (95% CI, 74‒94). Median (95% CI) duration of response was not reached (NR; 28.7‒NR) for patients with CR/CRi and 41.4 months (23.3‒NR) for all responders. Median (95% CI) progression-free survival was 31.4 months (20.1‒NR). In DL1+DL2, most common grade ≥3 treatment-emergent adverse events (TEAE) were neutropenia (52%) and anemia (41%). Cytokine release syndrome was reported in 80% of patients (grade 3, 4%; no grade 4/5), and neurological events in 41% (grade 3/4, 11%; no grade 5). Ibrutinib-related TEAEs were reported in 68% of patients (grade 3/4, 43%; no grade 5). Liso-cel plus ibrutinib demonstrated notable efficacy in patients with relapsed/refractory CLL/SLL with predictable and manageable safety. Clinicaltrials.gov: NCT03331198; NCT03435796.

ABSTRACT HLA‐C*03:760 differs from HLA‐C*03:04:01:01 by a single nucleotide substitution in exon 4 at codon 236.

ABSTRACT Introduction Multiple myeloma is a malignant plasma cell disorder predominantly affecting older adults and poses a significant health burden due to its incurable nature, high relapse rate, and associated immune dysfunction. Daratumumab, when added to standard therapy, has shown promising results in large trials. This meta‐analysis compared clinical trials of daratumumab‐containing regimens with standard therapies in the treatment of multiple myeloma. The primary outcomes analyzed were overall response rate (ORR) and progression‐free survival (PFS). Methods A systematic search of PubMed, Scopus, Cochrane CENTRAL, and Google Scholar was performed from January 2015 through December 2024. After screening via Rayyan, data were extracted on an Excel spreadsheet. Quality was assessed using the Cochrane RoB 2.0 tool. Eligible randomized controlled trials (RCTs) were included and analyzed using RevMan 5.4. Outcomes assessed were ORR and PFS. Adverse effects were compared among therapies. Results Nine Phase III RCTs ( n = 4556) were included, with a mean follow‐up of 44.3 months. Daratumumab‐based regimens significantly improved PFS (HR 0.55, 95% CI 0.46–0.66) but did not confer a statistically significant overall survival advantage (RR 0.90, p = 0.25). ORR was inconsistent, with five trials favoring daratumumab and one favoring control. Safety analyses showed higher risks of pneumonia (RR 1.74, p < 0.0001), secondary malignancies (RR 1.46, p = 0.003), neutropenia (RR 1.25, p = 0.006), and thrombocytopenia (RR 1.17, p = 0.01). Lymphopenia showed a numerical increase but was not statistically significant. Conclusion Daratumumab plus standard therapy regimens significantly improve PFS in multiple myeloma, though the overall survival benefit remains unproven. While efficacy is notable, treatment is associated with increased risks of infections, hematological toxicities, and secondary malignancies, highlighting the need for careful patient selection and vigilant monitoring. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Background The management of osteochondral lesions of the talus (OLT) is challenging, with 2 main options being conservative and surgical management. Orthobiologic therapies come to bridge the gap between these 2 options; however, inconsistencies in indication, composition, and heterogeneous evidence limit clinical decision-making. To address these challenges, 3 International Congress Meetings on Cartilage Repair of the Ankle were convened in Pittsburgh, USA (2017), Dublin, Ireland (2019), and New York, USA (2025) to establish agreement on the role of conservative management and injectable orthobiologic strategies in the treatment of OLT. Methods Seventy-five multidisciplinary experts from over 25 countries and 1 territory participated in a structured Delphi-based consensus process. Blinded surveys, structured questionnaires, and in-person discussions were used to develop and refine statements, supported by literature review and graded evidence (A1–E). Consensus strength was defined as consensus (51%-74%), strong consensus (75%-99%), or unanimous (100%) Results In total, 29 consensus statements were achieved across the 3 meetings. Strong agreement was reached regarding indications and expected outcomes of conservative management, including the role of immobilization and appropriate timing for surgical intervention. Orthobiologic injections, including platelet-rich plasma, concentrated bone marrow aspirate, and hyaluronic acid, were considered appropriate in select patients with persistent symptoms, although no superiority was demonstrated among formulations, preparation methods, or injection strategies. When used as adjuncts to surgical procedures, orthobiologics may improve radiological outcomes, with limited evidence for improvement in clinical outcomes. Technical considerations, including preferred harvest sites and a lack of standardized preparation protocols, were identified, along with key principles for patient counseling Conclusion These international consensus statements establish a standardized framework for the conservative management and use of injectable orthobiologic therapies in OLT. By clarifying indications, technical considerations, and current limitations, this work aims to improve consistency in clinical practice, guide treatment decision-making, and inform future research.

Abstract Background Immune dysregulation, immunosuppressive therapy and active inflammatory bowel disease (IBD) increase susceptibility to respiratory syncytial virus (RSV) infection. We evaluated the risk of RSV infection in patients with active and nonactive IBD. Methods Using the TriNetX Analytics Network from October 2024 through March 2025, we identified adult patients (aged ≥18 years) with IBD. Patients were classified as having active IBD if they had recent IBD complications, IBD-related surgery, or elevated inflammatory markers (within preceding 6 months); those without recent complications,surgeries, or elevated inflammatory markers were classified as having nonactive IBD within the same period. Outcomes were assessed within 180 days after the index date and included RSV infection, bacterial pneumonia, intensive care unit (ICU) admission, and mechanical ventilation. Results Among 141 763 patients (47 883 patients with active IBD, 93 880 patients with nonactive IBD), 2879 patients with active IBD and 3583 with nonactive IBD received the RSV vaccination. After matching, each cohort included 46 308 patients. Active IBD was associated with higher odds of RSV infection (adjusted odds ratio [aOR], 1.55; 95% CI, 1.18-2.04), bacterial pneumonia (aOR, 2.58; 95% CI, 2.08-3.19), ICU admissions (aOR, 2.07; 95% CI, 1.88-2.28), and mechanical ventilation (aOR, 2.41; 95% CI, 2.01-2.88). RSV risk remained higher among patients with active IBD both with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD (aOR, 1.26; 95% CI, 0.78-1.79). Conclusion Patients with active IBD had higher risk of RSV infection. Increased RSV risk was observed both among patients with active IBD with and without systemic corticosteroid exposure. Among RSV-vaccinated patients, RSV infection rates were not significantly different between active and nonactive IBD. Further prospective studies are needed to validate these findings.

Purpose of review Hepatorenal syndrome (HRS) is the extreme manifestation of acute renal dysfunction in patients with cirrhosis, resulting from systemic vasodilation and renal vasoconstriction, leading to a reduction in the glomerular filtration rate. Recent findings The diagnostic criteria redefined diagnostic criteria for HRS-AKI (Hepatorenal syndrome -Acute kidney injury) as our understanding of disease progression has improved. This understanding of the HRS disease process guides current management, with the combination of intravascular volume expansion and vasoconstrictor therapy being the cornerstone of treatment. In addition to treatment selection, timing of treatment initiation, duration, dosage, and monitoring during treatment are decisive factors in HRS outcomes. Pathogenesis of HRS-AKI may be different in patients with acute-on-chronic liver failure (ACLF) in comparison to decompensated cirrhosis. Unfortunately, outcomes remain poor with medical therapies alone and a high risk of disease recurrence exists for HRS-AKI with persistence of the cirrhotic milieu. Liver transplantation remains the only definitive treatment of HRS-AKI. Given the critical nature of HRS-AKI, a multidisciplinary approach involving hepatologists, nephrologists, and intensive care physicians is essential for optimal clinical management. Summary Patients with HRS-AKI should be managed ideally in tertiary care centers and referred for liver transplantation promptly when eligible.

Abstract Aims Nutritional counselling is a core component of cardiac rehabilitation (CR), yet the evidence base for specific dietary interventions within CR remains fragmented. This scoping review aimed to map the range of nutritional interventions evaluated in adult CR programmes, characterize their reported outcomes, and identify key gaps in current evidence and practice. Methods and results Following the Arksey and O’Malley framework and reporting according to PRISMA-ScR, a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception to June 2026. Eligible studies included randomized controlled trials, non-randomized trials, and observational studies evaluating an explicitly described nutritional intervention within a structured CR programme in adults with established cardiovascular disease. Of 2765 identified records, 35 studies met eligibility criteria. Interventions spanned Mediterranean and heart-healthy dietary patterns, calorie-restriction and weight-loss programmes, comprehensive lifestyle interventions, structured nutrition education and counselling, supplementation, functional foods, and individualized diet prescriptions. Across categories, improvements in body weight, central adiposity, and adherence to cardioprotective dietary recommendations were commonly reported, particularly when nutrition was delivered with repeated contact and individualized support. Effects on lipid profiles, inflammatory markers, blood pressure, functional capacity, and clinical outcomes were more variable. Conclusion Nutritional interventions within CR were most consistently associated with improvements in intermediate behavioural, anthropometric, and cardiometabolic outcomes, particularly when structured and reinforced over time. However, heterogeneity in study design, intervention delivery, comparator groups, outcome reporting, and follow-up duration precludes definitive conclusions about comparative efficacy, optimal intervention format, or the magnitude of benefit. Greater standardization, longer follow-up, and further evaluation of personalized nutritional strategies are needed to strengthen the nutritional component of CR.

Background: Platelet-rich plasma (PRP) is an emerging therapy that demonstrates potential benefits for knee osteoarthritis (OA); however, the accessibility of PRP remains limited, in part, because its use is not covered by insurance. Purpose: To identify factors contributing to health disparities in PRP treatment for knee OA using machine learning models. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The authors collected data from electronic medical records at 2 upper Midwest medical centers (Mayo Clinic and Detroit Medical Center) from 2022 to 2023 encompassing demographic, socioeconomic, and clinical factors. Data collection encompassed age, sex, race, ethnicity, area deprivation index, marital status, income, rurality, insurance, employment, language, religion, treatment site, and region. Logistic regression and random forest models were applied to 3667 samples (80% training, 20% testing), comparing PRP recipients against a standard care group. Models were evaluated using 10-fold cross-validation to ensure robust performance assessment. Results: Logistic regression revealed that increased age, widowed status, lower income, rural residence, unemployment/disability, and Medicaid/Medicare insurance were associated with lower odds of receiving PRP. Upper-middle income, contracted insurance, and treatment at the Mayo-Arizona and Mayo-Florida sites were associated with higher odds. The model achieved areas under the curve of 0.83 (training set) and 0.82 (testing set). Random forest analysis identified distance to care, age, area deprivation index, income, and treatment site as top predictors, with areas under the curve of 0.92 (training) and 0.87 (testing). Conclusion: The current study demonstrated that both models discerned key barriers (income, distance to care, retirement status) and facilitators (regional differences) affecting PRP accessibility. These findings provide potential policy initiatives aimed at improving PRP access for underserved demographics, offering a quantitative blueprint to foster equitable access to regenerative therapies for knee OA.