Multi-centre modified Delphi exercise to identify candidate items for classifying early-stage symptomatic knee osteoarthritis.

Objective: To generate a list of candidate items potentially useful for discriminating individuals with Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) from those with other conditions and from established osteoarthritis (OA), and to reduce this list based on expert consensus.

Design: We conducted a three-round online international modified Delphi exercise with OA clinicians and researchers ("OA experts"). In Round 1, participants reviewed 84 candidate items and nominated additional item(s) potentially useful for EsSKOA classification; those nominated by ≥3 participants were added.

Survival benefit of cytoreductive surgery in patients with primary stage IV endometrial cancer: a systematic review & meta-analysis.

Background: This systematic review and meta-analysis aimed to investigate the survival outcomes following cytoreductive surgery (CRS) in patients with primary stage IV endometrial cancer (EC).

Methods: We systematically searched the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Science for original studies reporting survival outcomes of primary stage IV EC after complete, optimal, and incomplete CRS. Pooled hazard ratios (HRs) for overall survival (OS) comparing optimal CRS with incomplete CRS were calculated using a random-effects model.

Acute effects of esketamine on hypoxic ventilatory response, haemodynamics, and brain function in healthy volunteers.

Background: The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v.

Preoperative methionine restriction induces perivascular adipose tissue browning and improves vein graft remodeling in male mice.

Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice.

The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

Explainable fully automated CT scoring of interstitial lung disease for patients suspected of systemic sclerosis by cascaded regression neural networks and its comparison with experts.

Visual scoring of interstitial lung disease in systemic sclerosis (SSc-ILD) from CT scans is laborious, subjective and time-consuming. This study aims to develop a deep learning framework to automate SSc-ILD scoring. The automated framework is a cascade of two neural networks.

The implication of TET1, miR-200, and miR-494 expression with tumor formation in colorectal cancer: through targeting Wnt signaling.

Objective: Colorectal cancer (CRC) is a diverse and multifaceted disease characterized by genetic and epigenetic changes that contribute to tumor initiation and progression. CRC pathophysiology has been linked to the deregulation of the Wnt signaling pathway and the ten-eleven translocation (TET) DNA demethylases. This study aimed to evaluate the expression level of selective miRNAs (miR-200 and miR-494), TET1, and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues.

Treatment of Conjunctival Melanoma Cell Lines With a Light-Activated Virus-Like Drug Conjugate Induces Immunogenic Cell Death.

Purpose: Conjunctival melanoma (CJM) is a rare malignant ocular surface tumor, which often leads to local recurrences and metastases. In murine models of subcutaneous tumors, treatment with a novel virus-like drug conjugate (VDC; Bel-sar) showed a dual mechanism of action with direct tumor cell killing as well as stimulation of an antitumoral immune response. Bel-sar is currently being evaluated for the treatment of primary uveal melanoma and indeterminate nevi in a phase III clinical trial.

Decompression without Fusion in Patients with Low-Grade Degenerative Spondylolisthesis and Stenosis: Long-Term Patient-Reported Outcome.

Background: One-third of patients with neurogenic claudication caused by lumbar spinal stenosis have low-grade degenerative spondylolisthesis. Decompression in these patients is considered a risk factor for instability, and it remains unclear whether instrumented fusion should be added. This study aims to assess the long-term clinical outcomes of decompressive surgery without instrumented fusion in patients with symptomatic spinal stenosis regardless of low-grade degenerative spondylolisthesis.

The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer.

Both type I interferon (IFN-I) and CD4 T-cell help are required to generate effective CD8 T-cell responses to cancer. We here outline based on existing literature how IFN-I signaling and CD4 T-cell help are connected. Both impact on the functional state of dendritic cells (DCs), particularly conventional (c)DC1.

Design of the VOILA-intervention study: A 12-week nutrition and resistance exercise intervention in metabolic or mobility compromised Dutch older adults and the response on immune-metabolic, gut and muscle health parameters.

Background: Exercise and nutrition interventions can slow ageing-induced decline in physiology. However, effects are heterogeneous and usually studied separately per outcome domain. In the VOILA study, we simultaneously study various health outcomes relevant for older adults and the inter-individual heterogeneity in response to a lifestyle intervention.

Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study.

Background: Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD).

Patients And Methods: Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT.

The longitudinal association of hand osteoarthritis with paid and unpaid work restrictions and related societal costs: The Hand Osteoarthritis in Secondary Care cohort.

Objectives: To investigate the course of restrictions in paid and unpaid work and corresponding societal costs in patients with hand osteoarthritis (OA).

Methods: Patients with data of at least baseline and one follow-up moment (year one up to year eight) of the Dutch Hand OSTeoArthritis in Secondary care cohort (HOSTAS) were included. The Health and Labour Questionnaire was used to assess over the last two weeks hand OA-related restrictions for paid and unpaid work.

The impact of the multicomponent "Healthy and Vital" 3-month lifestyle intervention in health professionals: a single group pre-(multiple) post-study.

Background: Working in healthcare often involves stressful situations and a high workload, and many healthcare workers experience burnout complaints or suffer from mental or physical problems. This also affects the overall quality of health care. Many previous workplace interventions focused on knowledge exchange instead of other health cognitions, and were not particularly effective.

Multi-omics analyses of cancer-linked clinical salmonellae reveal bacterial-induced host metabolic shift and mTOR-dependent cell transformation.

Salmonellae are associated epidemiologically and experimentally with colon cancer. To understand how Salmonella induces cell transformation, we performed multi-omics and phenotypic analyses of Salmonella clinical strains isolated from patients later diagnosed with colon cancer (case strains) and control strains from patients without cancer. We show that high transformation efficiency is a frequent intrinsic feature of clinical (case and control) salmonellae, yet case strains showed higher transformation efficiency than control strains.

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response.

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs) during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies.

External validation of SCORE2-Diabetes in the Netherlands across various Socioeconomic levels in native-Dutch and non-Dutch populations.

Aims: Adults with type 2 diabetes have an increased risk of cardiovascular events (CVE), the world's leading cause of mortality. The SCORE2-Diabetes model is a tool designed to estimate the 10-year risk of CVE specifically in individuals with type 2 diabetes. However, the performance of such models may vary across different demographic and socioeconomic groups, necessitating validation and assessment in diverse populations.

Approach to the patient with controlled acromegaly and acromegalic arthropathy: clinical diagnosis and management.

Following the description of an illustrative case of a 70-year-old female patient with longstanding active acromegaly and invalidating, progressive joint complaints, current insights regarding diagnosis, treatment, and long-term management of acromegalic arthropathy are summarized. Since clinical trials on this topic are lacking, the reported recommendations are based on extensive clinical and research experience with this clinical entity, and on established diagnostics and interventions in patients with other rheumatic diseases. The cornerstones of the management of acromegalic arthropathy remains normalization of growth hormone and insulin growth factor-1 levels.