ORTHOPAEDICS

Systemic sclerosis (SSc) is a prototypical inflammatory fibrotic disease involving inflammation, vascular abnormalities and fibrosis that primarily affect the skin and lungs. Of all the rheumatic diseases, SSc carries the highest all-cause mortality rate and represents an unmet medical need. In this review, we discuss the latest insights into the role of DNA methylation, histone modifications and non-coding RNAs in SSc and how these epigenetic alterations affect disease features. In particular, histone modifications have a role in the regulation of gene expression pertinent to activation of fibroblasts to myofibroblasts, governing their fate. DNA methyltransferases are crucial in disease pathogenesis by mediating methylation of DNA in specific promoters, regulating expression of specific pathways. We discuss targeting of these enzymes for therapeutic gain. Innovative epigenetic therapy could be targeted to treat the disease in a precision epigenetics approach.

Understanding Epigenetic Alterations in Systemic Sclerosis (SSc): Insights into DNA Methylation, Histone Modifications, and Non-Coding RNAs for Therapeutic Targeting

RHEUMATOLOGY

Study finds high supplement use and potential supplement–medication interactions among adults with systemic lupus erythematosus.

Dietary Supplement Use and Drug Interactions in SLE

A study of 451 adults with systemic lupus erythematosus found that 80.9% used at least one dietary supplement, with vitamin D, multivitamins and calcium most common. Nearly one-third (29.5%) had a supplement–medication combination with potential for interaction, highlighting the need for routine supplement review, particularly in patients with polypharmacy.

58.5% of US adults with arthritis reported moderate to severe joint pain in 2023, with no significant progress since 2019.

Joint Pain Remains Common Among US Adults With Arthritis

A 2023 analysis of US National Health Interview Survey data found that 58.5% of adults with diagnosed arthritis, or 30.8 million people, reported moderate to severe joint pain. Prevalence was higher among those with disability, poorer self-rated health, depressive or anxiety symptoms, COPD and cancer. Rates showed no significant improvement from 2019 to 2023.

ENDO-DIABETOLOGY

Study suggests improved proinsulin processing may lower HbA1c in type 2 diabetes without improving beta-cell compensation.

Proinsulin Processing May Improve Glucose Control in T2D

A randomized trial of 90 adults with type 2 diabetes found that adding meal-time insulin lispro or exenatide to basal insulin reduced HbA1c and the fasting proinsulin-to-C-peptide ratio without improving measures of insulin sensitivity or beta-cell compensation. Mediation analysis identified improved proinsulin processing as a potential driver of glucose lowering.

CARDIOLOGY

4D flow MRI could provide advanced assessment of aortic flow and transcatheter valve performance beyond conventional echocardiography.

4D Flow MRI for Transcatheter Aortic Valve Assessment

A review highlights the potential of 4-dimensional flow cardiac MRI to assess aortic flow after transcatheter aortic valve replacement beyond conventional pressure gradients. Metrics including flow displacement, flow reversal, wall shear stress and energy efficiency could help evaluate physiological flow restoration, ventricular remodeling and future valve performance, although clinical benefits remain unproven.

Study finds bipolar bone loss in one-third of adolescents with shoulder instability, with male sex and repeated dislocations as predictors.

Bipolar Bone Loss in Adolescent Shoulder Instability

A cohort study of 181 adolescents with anterior shoulder instability found bone loss in 74.6% at initial evaluation, including bipolar bone loss in 34.3%. Male sex and five or more prior dislocations independently predicted bipolar bone loss. Findings suggest that isolated Bankart repair may be insufficient for many adolescents with substantial bone loss.

Initial UNICORN and BATMAN results were favorable, but further studies are needed to optimize patient selection and long-term outcomes.

UNICORN and BATMAN Show Favorable Initial Results in Valve Procedures

Initial multicenter results for UNICORN and BATMAN, used to prevent coronary or LVOT obstruction during transcatheter valve procedures, were favorable. UNICORN achieved 94.2% procedural success, while BATMAN achieved 64%. Further studies are needed to refine patient selection and establish longer-term safety and outcomes.

TAVR reduced short-term complications and mortality versus SAVR in aortic stenosis with heart failure, but increased pacemaker use.

TAVR vs SAVR Outcomes in Aortic Stenosis With Heart Failure

A meta-analysis of 11 studies involving 63,022 patients with aortic stenosis and heart failure found TAVR was associated with lower acute kidney injury, myocardial infarction, hospital stay, and short-term mortality than SAVR. However, TAVR increased permanent pacemaker implantation, while long-term mortality did not differ significantly between the procedures.

Clopidogrel after PCI reduced MACCE, stroke, and myocardial infarction without increasing major bleeding or mortality.

Clopidogrel vs Aspirin After PCI: Lower Risk of Ischemic Events

A meta-analysis of five studies involving 17,010 patients found that clopidogrel monotherapy after DAPT following PCI with drug-eluting stents reduced major adverse cardiac and cerebrovascular events by 30% versus aspirin. Clopidogrel also lowered stroke and myocardial infarction risk, without significant differences in major bleeding or mortality.

TAVI lowered cardiovascular complications versus SAVR but increased pacemaker implantation and paravalvular regurgitation.

TAVI vs SAVR in Low-to-Intermediate Risk Patients: Umbrella Review

An umbrella review of 58 meta-analyses found that in low-to-intermediate-risk patients, TAVI was associated with lower cardiovascular mortality, atrial fibrillation, and acute kidney injury than SAVR across short- to mid-term follow-up. However, TAVI increased permanent pacemaker implantation and paravalvular regurgitation, while all-cause mortality remained similar.

NEUROLOGY

Thrombectomy improved 90-day functional outcomes in large-core stroke patients transferred from primary to comprehensive stroke centers.

Thrombectomy Benefits Large-Core Stroke Patients After Inter-Hospital Transfer

A post hoc analysis of the LASTE trial found that thrombectomy plus medical management improved 90-day functional outcomes compared with medical management alone in 157 patients with large-core anterior circulation stroke transferred from primary to comprehensive stroke centers. Benefit was seen across ASPECTS strata, including scores of 0–2.

CSF GDF15 showed high diagnostic accuracy for leptomeningeal metastasis from lung and breast cancers.

CSF GDF15 Shows Promise as a Biomarker for Leptomeningeal Metastasis

Objective
As leptomeningeal metastasis (LM) has a poor prognosis, reliable cerebrospinal fluid (CSF) diagnostic biomarkers are urgently needed. This study evaluated the diagnostic value of CSF growth differentiation factor 15 (GDF15) in LM from lung adenocarcinoma (LUAD) and breast cancer (BC).


Methods
A cohort of 726 CSF samples, including those from patients with LUAD LM, LUAD without LM (LUAD Non‐LM; comprising LUAD without brain metastasis and LUAD with parenchymal brain metastasis), neurological controls, and patients with primary intracranial solid tumors, as well as a BC cohort of 83 CSF samples from BC LM and BC Non‐LM patients, were enrolled in the study. The GDF15 and carcinoembryonic antigen‐related cell adhesion molecule 6 (CEACAM6) levels were measured by the chemiluminescence method.


Results
CSF GDF15 levels were elevated >25‐fold in LUAD LM compared with Non‐LM and neurological controls. CSF GDF15 excellently discriminated LUAD LM from Non‐LM (AUC 0.959 and 0.912) and neurological controls (AUC 0.975 and 0.929) in 2 independent cohorts. CSF GDF15 levels effectively distinguished LUAD LM from parenchymal brain metastasis (AUC 0.954) and primary intracranial solid tumors (AUC 0.950). High CSF GDF15 levels were associated with shorter overall survival in LUAD LM patients. CSF CEACAM6 similarly differentiated LUAD LM from parenchymal brain metastasis (AUC 0.956) and primary intracranial solid tumors (AUC 0.970). In the BC cohort, GDF15 (AUC 0.899) and CEACAM6 (AUC 0.869) both performed well in distinguishing LM from Non‐LM. The combination of GDF15 and CEACAM6 outperformed either biomarker alone in diagnosis of LUAD LM and BC LM.


Interpretation
CSF GDF15 is a high‐performance diagnostic biomarker for LUAD LM and BC LM. ANN NEUROL 2026 ANN NEUROL 2026

UROLOGY

Gonadotropin therapy restored sperm production in 74% and supported pregnancy in 52% of couples with male hypogonadism.

Gonadotropin Therapy Boosts Fertility in Male Hypogonadism

A systematic review of 50 studies involving 1,583 men with hypogonadotropic hypogonadism and azoospermia found that gonadotropin therapy induced spermatogenesis in 74% of patients, with sperm production taking about 12 months on average. Pregnancy occurred in 52% of couples, while combined gonadotropin therapy outperformed hCG alone.

GASTROENTEROLOGY

UDFF accurately detected liver steatosis in children, offering a non-invasive approach for MASLD screening and monitoring.

UDFF Shows High Accuracy for Detecting MASLD in Children

A prospective study of 70 children found that ultrasound-derived fat fraction (UDFF) closely matched MRI-PDFF for detecting liver steatosis. UDFF showed strong correlation with MRI-PDFF and achieved 97.6% sensitivity and 92.9% specificity for detecting steatosis, supporting its potential as a non-invasive, reproducible tool for screening, staging, and monitoring paediatric MASLD.

Baseline testosterone did not predict the severity of body composition, physical, energy or sexual changes during ADT.

Baseline Testosterone Does Not Predict ADT Side Effects

A study of 39 men receiving 24 weeks of androgen deprivation therapy (ADT) for prostate cancer found substantial increases in fat mass and declines in lean mass, physical function, energy, and sexual desire. However, pretreatment testosterone levels were not associated with the severity of these changes, suggesting baseline testosterone does not predict ADT-related adverse effects.

One year of GAHT increased upper-body strength in transmasculine people but reduced strength and power in transfeminine people.

GAHT Changes Upper-Body Muscle Strength and Power

A prospective study of 92 transgender people found that 1 year of gender-affirming hormone therapy produced opposite changes in upper-body muscle performance. Maximal strength increased by 12% in treatment-naïve transmasculine participants, while it decreased by 23% in treatment-naïve transfeminine participants, accompanied by a 23% reduction in muscle power.

Advances in epigenetics i...

Advances in epigenetics in systemic sclerosis: molecular mechanisms and therapeutic potential