Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent and severe liver disease globally, encompassing a spectrum from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. The multifaceted pathogenesis of MASH, particularly in the setting of obesity and type 2 diabetes mellitus (T2DM), has resulted in the exploration of pharmaca that target metabolic, inflammatory, and fibrotic processes. Until quite recently, demonstrating efficacy in phase 3 trials with single agents has been challenging. Multiple combination trials have been conducted, often requiring complex multi-arm designs, but demonstrating limited additive benefit over monotherapy. The recent conditional approval of two monotherapies targeting metabolic pathways, the thyroid hormone receptor beta agonist (THRβ) resmetirom and the glucagon-like peptide 1 receptor agonist (GLP1 RA) semaglutide, is kickstarting the therapeutic armamentarium for MASH. Other promising monotherapies may follow in the near future, in particular fibroblast growth factor 21 (FGF21) analogues and pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor. As a result, the position of combination therapy in MASH may shift toward add-on strategies evaluated in clinical practice rather than pharma-driven trial settings. The four monotherapy classes mentioned may be applied in combination, as is already occurring with resmetirom and semaglutide. In this review, we break down the rationale for the various combinations. In addition, we highlight the unmet need for effective antifibrotic therapies and discuss future directions for combination therapy in MASH. Based on the available data, we provide recommendations for the most promising combination strategies.

Young children with type 1 diabetes are often marginalized in clinical consultations due to communication practices that favor verbal, adult-centered interaction. Developmentally attuned methods to support young children's meaningful participation in routine diabetes care remain limited. This study aimed to develop and examine Child-Centered Narrative Play Tools (CNPTs) and explore how they support participation, communication, expression of agency, and assess their feasibility in pediatric diabetes consultations.

An iterative participatory qualitative design was conducted across two specialist pediatric diabetes clinics in Denmark. Twenty-nine children aged 3-7 years, 29 caregivers, and 12 healthcare professionals participated in workshops, exploratory testing, video-recorded clinical observations, and semi-structured interviews. Narrative story stems and play materials were co-developed and refined through cycles of testing and feedback. Data were analyzed using thematic analysis, combining inductive coding with theory-informed interpretation.

Narrative play functioned as a primary medium through which young children expressed experiences, demonstrated understanding of diabetes management, and exercised agency during consultations. The tools enabled children to articulate everyday experiences of diabetes management and emotional responses that were often not expressed in standard consultations. Healthcare professionals reported increased confidence in communicating at the child's developmental level, and caregivers observed greater ownership and recall of consultation content. Feasibility testing indicated that the tools were feasible for routine clinical practice, with high acceptability and good usability following appropriate training.

Child-Centered Narrative Play Tools (CNPTs) offer pediatric HCPs a feasible, theory-informed framework to operationalize child-centered care and make young children's perspectives visible and actionable in routine diabetes practice.

Anti-cytokine autoantibodies are increasingly recognized as modulators of immune function and determinants of disease risk, yet their genetic basis and population-level impact remain unclear. Here we perform genome-wide association studies of autoantibodies against IL-1α, IL-6, IL-10, IFN-α, IFN-β, IFN-γ and GM-CSF in 15,000 individuals from the Danish Blood Donor Study. We identify 52 genome-wide significant loci, implicating genes enriched in antigen-presentation pathways. Using these data, we derive cytokine-specific polygenic risk scores and evaluate their associations across 300,000 individuals in the Copenhagen Hospital Biobank. Genetic predisposition to IL-1α autoantibodies is associated with reduced risk of rheumatoid arthritis and certain cancers, whereas genetic predisposition to IL-6 autoantibodies is associated with increased risk of diabetes, mirroring prior clinical observations. These findings define the genetic architecture of anti-cytokine autoantibodies and indicate their divergent effects on human disease risk at population scale, providing a framework for mechanistic investigation and potential clinical stratification.

Multiple myeloma (MM) is a chronic haematological malignancy caused by the proliferation of malignant plasma cells in the bone marrow and overproduction of monoclonal antibodies. While no cure is available, treatments aim to control the disease and place patients into remission.

This research aimed to explore the psychological impact and healthcare experiences of patients affected by triple-class refractory (TCR) MM. This research formed part of a wider qualitative study examining the experiences of newly diagnosed, double-class exposed and TCRMM patients.

This qualitative, semi-structured interview study using Interpretative Phenomenological Analysis examined patient experiences. Patients were recruited through Myeloma UK, a charity for patients with MM and carers.

Seven patients diagnosed with TCRMM (five men and two women), aged 41-84 years (M=60 years, 3 months, SD=15 years) provided written consent. Two patients had become TCRMM within 6-12 months of MM diagnosis, one patient within 1-5 years and four patients over 5 years. Three overarching themes were identified that captured the key unmet needs of those affected by TCRMM: (1) Matching psychological support to specific moments identified drivers for regular psychological input at key points in the patient pathway; (2) Finding a voice in treatment decisions reflected patients' perceived lack of involvement in treatment decisions and their desire to be more engaged; and (3) Learning to navigate clinical trials highlighted the challenges associated with accessing transparent information about trials and the complexities of eligibility criteria.

The results demonstrate the psychological burden of TCRMM and the associated treatments across patient management and/or care. Likewise, patient access to informative materials and practical tools to support engagement in informed decision-making, specifically around treatments and clinical trials, needs to be more routinely offered and made available.

Although clinical trials showed outcomes improvement in MCL, their applicability to real-world practice remains limited. Using the prospective REALYSA registry (NCT03869619), we evaluated contemporary management, highlighting evolving practices and differences by age. Among 295 patients, 63% were ≥ 65 years, 48% had a high-risk MIPI score with Ki-67 ≥ 30% in 53% and aggressive morphology in 11%. Younger patients received high-dose cytarabine (93%) and ASCT (78%). Older patients were treated with bendamustine-rituximab (28%), R-CHOP (18%), and low-dose cytarabine (20%). Two-year event-free (EFS-2y) and overall (OS-2y) survivals were 80% and 89% in < 65y; 60% and 77% in ≥ 65y. Among 238 patients responders after induction, rituximab maintenance (RM) use was frequent but lower in older patients (88% vs. 76%). In time-dependent Cox models adjusted for age (< 65 vs. ≥ 65) and MIPI, RM was associated with a lower hazard of EFS events (HR 0.48; 95% CI: 0.25-0.92), although residual confounding related to treatment selection may remain. In the second-line setting (n = 72), most patients were POD24 (89%) and 56% received ibrutinib, yet outcomes remained poor (CR 24%, ORR 35%, median EFS and OS of 6.3 and 25.6 months, respectively). These findings underscore the need for improved strategies for older and high-risk patients. Retrospective landmark analyses suggest a potential association between RM and improved EFS but are limited by baseline differences between groups.

Sarcopenia, characterized by loss of skeletal muscle mass and function, has emerged as a potential prognostic biomarker in oncology. Its role in patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs) remains inadequately defined.

A systematic review and meta-analysis was conducted in accordance with PRISMA 2020. PubMed, Scopus, and the Cochrane Library were searched from inception to March 2026. Observational studies reporting baseline computed tomography (CT)-defined sarcopenia, based on a dichotomized skeletal muscle index (SMI) or skeletal muscle area (SMA), in adults with HNSCC receiving ICIs were included. Studies using non-radiological assessment, continuous-only muscle indices, exposure definitions incorporating on-treatment change, or populations restricted to progression after ICI therapy were excluded, and cohorts were screened for patient overlap. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using a random-effects model with the Hartung-Knapp-Sidik-Jonkman (HKSJ) method incorporating the truncated variance correction. Risk of bias was assessed with the QUIPS tool and certainty of evidence with GRADE as adapted for prognostic factor reviews.

Three retrospective cohort studies (354 patients) met the eligibility criteria. Under the pre-specified primary estimator the pooled hazard ratio for OS was 2.05 (95% CI 1.00-4.20), an interval that marginally includes the null (common-effect HR 2.05, 95% CI 1.48-2.84; I² = 0%); for PFS it was 1.85 (95% CI 1.05-3.27; I² = 0%), excluding the null only narrowly. The wide HKSJ intervals reflect the small number of studies. The pooled OS estimate is closely concordant with an independent published synthesis of the same question (HR 2.05). Certainty of evidence was rated low for both outcomes.

Baseline CT-defined sarcopenia was associated with an approximately two-fold increase in the hazard of death, and of progression or death, in patients with HNSCC treated with ICIs. The primary OS analysis did not reach conventional statistical significance: under the pre-specified HKSJ estimator its 95% confidence interval marginally included the null, and the PFS interval excluded the null only narrowly. The association therefore rests on the size and consistency of the point estimates, the absence of heterogeneity, the common-effect interval and concordance with an independent published synthesis, rather than on the primary interval alone. The evidence base comprises three retrospective cohorts and certainty is low. Sarcopenia should be regarded as a prognostic rather than a predictive marker in this setting and must not be used to justify withholding immunotherapy. Prospective studies with standardized CT-based definitions are required.

Rheumatological diseases such as myositis might be detected during the diagnostic process of lung cancer.This suggests the need for interdisciplinary dialogue concerning thoracooncological and immunosuppressive treatment of myositis and associated interstitital lung diseases. In particular, the side effects of checkpoint inhibitors must be taken into consideration.This case report is about the detection of myositis-associated interstitial lung disease in the course of a thoracooncological treatment regimen.

Pheochromocytomas (PCCs) in dogs are challenging to diagnose. Plasma proteomics offers a minimally invasive approach to identify circulating biomarkers and disease-relevant pathways.

To compare the plasma proteome of dogs with PCC and controls to (1) identify differentially abundant proteins, (2) characterize altered pathways, and (3) nominate candidate circulating biomarkers and therapeutic targets.

Plasma from 10 client-owned PCC dogs and 10 healthy controls.

Multicenter, retrospective, observational, exploratory study using label-free liquid chromatography-mass spectrometry. Primary outcomes were the identification of differentially abundant proteins and characterization of altered pathways and protein functions.

Principal component analysis demonstrated clear separation between PCC and control dogs. Of 261 reliably quantified proteins, 51 were differentially abundant (false discovery rate-adjusted P < .05). Of these, 33 had a log2 fold change of >1 or < -1, with 15 showing higher and 18 lower plasma abundance in PCC. Compared with controls, PCC dogs showed increased abundance of proteins linked to cell adhesion/migration and metastatic potential, hemostasis, and regulation of apoptotic signaling, alongside alterations in oxidative stress and metabolic processes. Several proteins with higher abundance, including CD44, peroxiredoxin-2, and peptidyl-prolyl cis-trans isomerase, emerged as promising candidates for therapeutic exploration.

Dogs with PCC exhibit a distinct circulating protein signature vs healthy controls, providing clues to PCC pathogenesis and nominating proteins as diagnostic biomarker candidates and potential therapeutic targets.

Immune checkpoint inhibitor (ICI) responses in esophageal squamous cell carcinoma (ESCC) are highly variable, and the immune mechanisms underlying therapeutic sensitivity remain unclear. Here we show, using single-cell RNA, T-cell receptor and whole-exome sequencing of 52 ESCC patients from a phase 3 neoadjuvant trial, that treatment response is associated with coordinated tumor microenvironment remodeling. Responders exhibit increased abundance and clonal enrichment of cytotoxic CX3CR1⁺CD8⁺ T-cell clonotypes, accompanied by reduced frequency and clonal dominance of exhausted CXCL13⁺CD8⁺ T-cell states after treatment. CX3CR1⁺CD8⁺ T-cell accumulation is associated with CX3CL1-CX3CR1 signaling and supported by functional, mouse-model and peripheral blood validation. Genomic analyses link higher cancer cell fraction mutation burden and neoantigen abundance to response, consistent with post-treatment immune editing. Tumor epithelial differentiation states and stromal remodeling are also associated with therapeutic outcome. These findings identify a response-associated CX3CR1⁺CD8⁺ cytotoxic effector state that may inform neoadjuvant ICI-based therapy in ESCC.