Infectious diseases can cause lasting immune disturbances, but whether they contribute to later inflammatory bowel disease (IBD) is unclear. Hospital-treated infections may be especially informative because they reflect substantial immune challenge, yet their relation to IBD risk and the role of host genetics remain poorly defined. It examines hospital-treated infections and incident IBD in a prospective cohort and integrates gene-environment interaction analyses to identify susceptibility pathways and develop a post-infection risk score. Hospital-treated infections of multiple pathogen types and sites were associated with higher subsequent IBD risk. This association is stronger in carriers of immune-related risk variants, with Crohn's disease linked mainly to innate immune and autophagy pathways and ulcerative colitis to JAK-STAT, T-cell differentiation, and chemokine signaling. An Infection IBD Score based on 44 immune-related genes stratified post-infection risk. These findings support infections as triggers of IBD in genetically susceptible individuals and highlight a potential tool for risk stratification.

VEXAS syndrome is characterized by a complex spectrum of inflammatory and hematologic manifestations. Clinical research to identify effective therapies is urgently needed but is hindered by the lack of validated outcome measures. A VEXAS-specific disease activity index (DAI) is an essential tool for reliably capturing changes in disease activity over time, thereby supporting clinical research and informing patient care in this emerging disease. This study aimed to develop a comprehensive DAI to assess disease-related inflammation across affected organ systems in patients with VEXAS syndrome.

Inflammatory manifestations of VEXAS were previously identified through a systematic literature review and expert input. A multinational expert advisory committee developed the VEXAS-DAI using modified Delphi methodology until consensus (defined as ≥75% concurrence) was reached. Item grading was adapted from the Common Terminology Criteria for Adverse Events (CTCAE) criteria. Scoring criteria were developed based on 158 test cases using the Physician Global Assessment of Inflammation.

Consensus on the VEXAS-DAI was achieved after four Delphi rounds. The index assesses inflammatory activity at the time of evaluation across 12 domains: inflammatory rash, chondritis, periorbital, ophthalmologic, joint, pulmonary, cardiovascular, genitourinary, neurological, oral and gastrointestinal, renal, and constitutional symptoms. The total score ranges from 0 to 40.

The VEXAS-DAI is a novel instrument designed to quantify active inflammation over time in patients with VEXAS syndrome. Prospective validation within a clinical trial setting is ongoing.

Safety and efficacy of HRT in women with chronic medical conditions remain incompletely understood. As life expectancy rises and the use of HRT becomes more common, condition-specific recommendations are crucial to support clinical decisions.

Systematic review on disease-specific effects of HRT in peri- and postmenopausal women with chronic medical disorders.

Comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was conducted from inception to 31 August 2025. Cross reference was undertaken.

Systematic reviews, meta-analysis, Randomised controlled trials, cohort, and case-control studies examining oral, transdermal, or other HRT formulations in peri- or postmenopausal women with chronic diseases were included. Case reports, editorials, conference abstracts, and non-English publications were excluded.

Titles, abstracts, and full-text articles were independently evaluated by three reviewers. Data extraction included study design, participant characteristics, HRT regimen, and outcomes.

Fifty-four studies met inclusion criteria, covering neurological (epilepsy, migraine, Alzheimer's, Parkinson's, multiple sclerosis, meningioma), metabolic, cardiovascular, autoimmune, renal, hepatic, and endocrine conditions. Oral estrogen formulations may increase risk whereas transdermal preparations may confer lower thrombotic and hepatic risk (limited evidence). Neurological benefits were observed in Parkinson's disease and multiple sclerosis, but evidence was limited for Alzheimer's disease and migraine. HRT was generally safe in stable autoimmune conditions. Cardiovascular safety is supported in women without pre-existing disease.

HRT should be individualised according to comorbidities, formulation, and route, with preference for transdermal or low-dose regimens in high-risk populations.

Registration: PROSPERO ID CRD420251233527.

Surgical resection remains a cornerstone in the treatment of various hepatobiliary diseases. However, preoperative quality of life (QoL) in patients undergoing liver resection remains insufficiently studied. This study aimed to evaluate preoperative QoL and identify factors associated with impaired QoL in patients scheduled for liver surgery.

This single-center prospective observational study included patients undergoing liver resection for hepatobiliary diseases. Preoperative QoL was assessed using the Short Form-36 (SF-36) Health Survey, comprising eight domains and the Physical and Mental Component Summary (PCS and MCS) scores. Scores were compared with reference values from the 1998 German Federal Health Survey. Univariate and multivariable linear regression analyses were performed to identify preoperative predictors of QoL.

159 patients were included in the final analysis. Of these, 20 (12.6%) had benign lesions, 80 (50.3%) primary malignant tumors, and 59 (37.1%) secondary malignant tumors. Compared with the general German population, patients demonstrated significantly lower scores in 7 of 8 SF-36 domains as well as in both summary scores. Multivariable analyses identified female sex, absence of preoperative chemotherapy, anemia, history of depression, cardiovascular disease, and renal disease as independent predictors of impaired QoL across multiple domains. The mean R² across all multivariable models was 0.23.

Patients awaiting liver resection exhibit substantially impaired QoL compared with the general population. A combination of demographic, clinical, and laboratory factors influences preoperative QoL. Recognition of these factors may facilitate risk stratification, improve preoperative counseling, and support targeted interventions for patients at increased risk of impaired QoL.

Chronic venous insufficiency (CVI) produces heterogeneous lower-extremity skin changes that often mimic inflammatory dermatoses, complicating the differentiation between venous etiologies and conditions requiring dermatologic care. Coexisting venous signs further confound visual interpretation, leading to diagnostic variability. To address this unmet clinical need, we developed and externally validated a pose-guided, high-resolution deep learning pipeline to classify CVI-related skin lesions from routine clinical photographs.

A deep learning framework was developed using a multicentre dataset (8672 images) from Korea University Guro Hospital, Chung-Ang University Gwangmyeong Hospital and Heartwell Vein Clinic. The pipeline integrated Sapiens-based pose estimation for limb localization and a U-Net model refined with Segment Anything Model 2 (SAM2) for skin segmentation. Multiple backbone architectures were evaluated, and ResNet-34 was selected based on optimal performance, taking refined masks and RGB images as input. Performance was evaluated on an internal test set, an independent clinical dataset (n = 183), and the Fitzpatrick17k dataset.

ResNet-34 emerged as the optimal architecture, achieving an internal AUROC of 0.922 with balanced sensitivity (0.679) and specificity (0.943) at 1024 × 1024 resolution. Pose-guided skin segmentation improved discrimination compared to using raw images (AUROC 0.920) or skin masking alone (AUROC 0.905). Multicentre training enhanced generalizability, yielding an external AUROC of 0.877 and maintaining high performance on the Fitzpatrick17k dataset (sensitivity 0.918).

Our pose-guided, high-resolution pipeline enables robust, objective detection of CVI-related skin lesions. By demonstrating high generalizability across multicentre and public datasets, this framework serves as a reliable decision-support tool to standardize clinical phenotyping and facilitate consistent triage and management of chronic venous disease across diverse care settings.

To report an atypical phenotype associated with two rare COL4A1 glycine missense variants located in exon 23.

Clinical, neuropsychological, and brain imaging data of four patients with such variants were reported.

Four unrelated patients presented with late-onset cognitive alterations starting between 55 and 65 years of age. Brain magnetic resonance imaging (MRI) showed extensive white-matter hyperintensities on T2 or Flair images in all subjects, associated with multiple dilated perivascular spaces in the basal ganglia with features of status cribrosum in the three oldest individuals. None of the patients had a history of haemorrhagic stroke. Three of these patients had previously experienced mood disturbances. All had a family history of depression and/or suicide. Three of these unrelated patients shared a rare missense variant p.(Gly474Arg) in COL4A1, whereas the fourth one carried a p.(Gly486Glu) variant; these two variants affect two closely linked glycine residues encoded by exon 23 and located in a major cell-binding site of the triple helix.

Missense variants affecting closely clustered glycine residues within the glycine-X-Y repeats encoded by exon 23 of COL4A1 are associated with an atypical, late-onset form of cerebral small vessel disease, characterised by diffuse leukoencephalopathy with a status cribrosum pattern and predominantly cognitive and/or neuropsychiatric manifestations.

Incretin mimetics are increasingly prescribed for the treatment of overweight and obesity, resulting not only in significant weight reduction but also co-occurring improvements in cardiovascular health and quality of life. Incretin mimetic use among older adults is expected to increase as the population ages into obesity. However, older adults experience accelerated losses in skeletal muscle mass and bone mineral density, and it remains unclear how incretin mimetics affect these processes. This review outlines the age-associated changes in muscle and bone and explores current evidence reporting the effects/associations of incretin mimetics on these tissues, as well as on physical function and fragility fracture risk. We identified several incretin mimetic weight reduction trials that demonstrated significant losses in lean soft tissue (n = 6 studies) and/or indices of bone (n = 3); however, the clinical significance of these decrements on physical function and/or fragility fracture remains unclear. Considering a rising trend in the prescription of incretin mimetics to treat obesity in older adulthood, a more robust characterization of the impact of these medications on lean soft tissue, physical function, and fragility fracture is needed to support future clinical decision-making in older adults with overweight/obesity.

The activation of endoplasmic reticulum stress (ERS), specifically the PERK/eIF2α/CHOP signaling, is a recognized consequence of ischemic stroke. However, the roles and mechanisms of CRM-1 regulating ERS in stroke are poorly elucidated. A murine model of stroke was generated via transient middle cerebral artery occlusion (MCAO). The endpoints included TTC-derived infarct volume, H&E/TUNEL histopathology, p-PERK immunohistochemistry, and Western blot. Oxygen-glucose deprivation/reoxygenation (OGD/R) was employed in HT22 neurons. The CRM1-ALKBH5 interaction and subcellular distribution were assessed by co-immunoprecipitation (co-IP), cytoplasm-nucleus fractionation, and confocal microscopy. m⁶A regulation of BANF1 was examined using MeRIP-qPCR, RIP-qPCR, and a dual-luciferase reporter assay. Knockdown of CRM-1 reduced the infarct size, decreased ER stress activation, decreased apoptosis in vivo, and improved cell viability after OGD/R. CRM-1 was attached to ALKBH5 and promoted its export from the nucleus, which increased m⁶A modification and expression on BANF1. IGF2BP2 and YTHDF1, respectively, enhanced the stability and translation of BANF1 mRNA, thereby upregulating its expression. BANF1 overexpression restored PERK/eIF2α/CHOP activation and apoptosis in the CRM-1 knockdown context. CRM-1 exacerbated ischemic stroke injury by exporting ALKBH5 to upregulate BANF1 in an m⁶A-IGF2BP2/YTHDF1-dependent manner. This cascade subsequently activated the PERK/eIF2α/CHOP ERS pathway.

Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-β) superfamily, thereby regulating diverse physiological processes, including regulation of skeletal muscle, adipose, and bone homeostasis. FST also promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles and metabolic health in mice. Given the emerging association between brown adipose tissue (BAT) activation and reduced atherosclerosis, we investigated the anti-atherogenic potential of FST. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area and positively correlated with the expression of multiple adipose browning-associated genes. Adeno-associated viral delivery of Fst (AAV1-FST344) in Ldlr^-/- mice significantly reduced aortic lesion area, improved plasma lipid profiles, and decreased expression of adhesion (VCAM1) and inflammatory (iNOS, TNF-α) markers in white adipose tissue (WAT), liver, and heart. Fst gene delivery also markedly increased uncoupling protein 1 (UCP1) expression in WAT, consistent with WAT browning. Integrated correlation analyses of Fst expression with tissue metabolites, together with plasma metabolite-lesion associations identified in the HMDP, implicated the arginase 1 (Arg1)-mediated metabolic pathway as a key regulator of atherogenesis. Consistent with these findings, Arg1 expression was significantly elevated in WAT, liver, and heart of AAV1-FST344-treated mice and in wild-type versus Fst-knockout mouse embryonic fibroblasts (MEFs). Immunostaining localized Arg1 predominantly to CD68⁺ macrophages in heart and liver. Given recent evidence identifying Arg1 as a novel mediator of efferocytosis, these findings suggest that Arg1 may promote macrophage metabolic reprogramming and resolution of inflammation by enhancing the clearance of apoptotic cells. Furthermore, Fst gene delivery increased the expression of fibroblast growth factor 21 (Fgf21) and adiponectin (AdipoQ) in WAT. Collectively, these findings identify Fst as a novel anti-atherogenic regulator that protects against vascular disease by promoting adipose browning, improving lipid metabolism, and activating Arg1-mediated metabolic pathways.