Exploring the relation between TGF-β pathway activity and response to checkpoint inhibition in patients with metastatic melanoma.

Introduction: Immune checkpoint inhibition (ICI) is highly effective for the treatment of melanoma, but intrinsic resistance is present in a subgroup of patients. TGF-β pathway activity may play a role in this resistance by preventing T-cells from entering the tumor microenvironment, causing immune escape. We investigated the association of TGF-β signal transduction pathway activity with resistance to ICI treatment in advanced melanoma.

Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial.

Background: RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).

Patients And Methods: Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab.

Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.

Introduction: Knowledge about the distribution and frequency of the respective haplotypes on the wildtype and mutant allele is highly relevant in the context of future gene therapy clinical studies in Spinocerebellar Ataxia Type 3, the most common autosomal dominantly inherited ataxia. Single nucleotide polymorphisms associated to the disease-causing gene, ATXN3, have been determined. We wanted to investigate the frequency and regional distribution of two intragenic single nucleotide polymorphisms (SNPs) in a large European SCA3 cohort and their relation to the clinical phenotype.

Diagnosing primary lateral sclerosis: a clinico-pathological study.

Background:  Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by upper motor neuron degeneration, diagnosed clinically due to the absence of a (neuropathological) gold standard. Post-mortem studies, particularly TDP-43 pathology analysis, are limited.

Methods: This study reports on 5 cases in which the diagnostic criteria for PLS were met, but in which neuropathology findings showed (partially) conflicting results.

Muscle contractile properties and perceived fatigue in the general and diseased population.

Knowledge of muscle contractile properties, physical fitness, and their associations with perceived fatigue may provide insights into mechanisms inducing fatigue and treatment targets. We aimed to identify differences in contractile properties and physical fitness between populations, and examine associations with perceived fatigue. We pooled data on perceived fatigue, physical fitness, and contractile properties from six studies, including a control group (n = 90), cancer survivors (n = 27), patients with chronic obstructive pulmonary disease (COPD; n = 16), chronic myeloid leukemia (CML; n = 20), and statin users (n = 64).

The frequency and impact of drug-related problems with postoperative medication reported by orthopaedic patients after discharge.

Unlabelled: Following orthopaedic surgery, medication is vital for recovery and preventing complications, however drug-related problems (DRPs) can hinder medication use. The prevalence, types, and impact of DRPs on patients' activities of daily living (ADL) and the medication involved are unknown. Insight is needed for targeted interventions.

Gender issues in myopia: a changing paradigm in generations.

Myopia is becoming an important cause of visual impairment. Determining risk profiles will help to develop targeted prevention strategies. This study aims to explore the difference in myopia development between genders in two cohorts representing different generations, and to assess whether hypothetical interventions targeting education or lifestyle factors would reduce a gender gap.

Advances in tuberculosis biomarkers: unravelling risk factors, active disease and treatment success.

Tuberculosis (TB) is a major global health threat and demands improved diagnostic and treatment monitoring methods. Conventional diagnostics, such as sputum smear microscopy and culture, are limited by slow results and low sensitivity, particularly in certain patient groups. Recent advances in biomarker research offer promising solutions in three key areas: risk of disease, diagnosis of active disease and monitoring of treatment response.

The Utility of Total Thrombus-Formation Analysis System (T-TAS) in the Thrombosis and Hemostasis Field: A Scoping Review.

Background: A wide variety of laboratory hemostasis tests is available, but the majority is plasma-based, static and unable to assess platelet function and fibrin formation simultaneously. The Total Thrombus-Formation Analysis System (T-TAS) is a microchip-based flow chamber system that simulates in vivo conditions for evaluating whole blood thrombogenicity.

Aim: A comprehensive overview of its applicability in different thrombosis and hemostasis related clinical situations is lacking and therefore this scoping review was performed.

Nails and skin co-infection by Fusarium verticillioides and Proteus vulgaris secondary to arterial occlusion of lower extremity.

Background: Post-traumatic Fusarium infection is rare. Arterial occlusive disease, a common vascular disorder in the elderly, often leads to ischemic necrosis of the lower extremities, which in turn increases the likelihood of secondary infections. Those secondary infections can be caused by bacteria, virus, or fungi.

Plasma proteomics improves prediction of coronary plaque progression.

Aims: Coronary computed tomography angiography (CCTA) offers detailed imaging of plaque burden and composition, with plaque progression being a key determinant of future cardiovascular events. As repeated CCTA scans are burdensome and costly, there is a need for non-invasive identification of plaque progression. This study evaluated whether combining proteomics with traditional risk factors can detect patients at risk for accelerated plaque progression.

Patient experiences with person-centred and integrated chronic care, focussing on patients with low socioeconomic status: a qualitative study.

Background: effectiveness of single disease management programs (DMP) in general practice may be limited for patients with low socioeconomic status (SES), as DMPs insufficiently take into account the specific problems and needs of this population. A Person-Centred Integrated Care (PC-IC) approach focusing on patient's needs could address these problems.

Aim: to explore experiences of patients with (multiple) chronic diseases with regard to the acceptability of a general practice-based PC-IC approach, with a focus on patients with low SES, and to establish which modifications are needed to tailor the approach to this group.

MIP4IBD: An Easy and Rapid Genotyping-by-Sequencing Assay for the Inflammatory Bowel Diseases Risk Loci.

Background: Inflammatory bowel diseases (IBD) are polygenic, with many genetic variants contributing to disease risk. Knowing the genotype of specific variants or calculating a combined genetic risk score benefits translational and functional research. To address this, we developed MIP4IBD, a flexible and cost-effective genotyping-by-sequencing assay using molecular inversion probes (MIPs).

Predictors of coronary atherosclerosis in middle-aged and older athletes: the MARC-2 study.

Aims: Exercise improves cardiovascular health, but high-volume high-intensity exercise is associated with increased coronary artery atherosclerosis and calcification (CAC). We aimed to identify predictors of CAC in athletes.

Methods And Results: We assessed the association of traditional and non-traditional cardiovascular risk factors with CAC using linear and logistic regression.

Lung ultrasound in pneumonia: a guide for effective implementation.

In patients with pneumonia, lung ultrasound is a useful diagnostic and monitoring tool and has been proven to be superior to physical examination and chest X-ray in terms of feasibility and diagnostic accuracy. Guidelines do not address lung ultrasound as part of the diagnostic workup or as monitoring tool which is surprising. This article provides a succinct overview on the currently available evidence on efficacy and utility of lung ultrasound in patients with a clinical suspicion of pneumonia.

The Correlation Between Fear Avoidance Beliefs and Physical Activity in Unilateral Vestibulopathies.

Background And Purpose: In individuals with unilateral vestibulopathy (UVP), physical activity (PA) is recommended to stimulate central vestibular compensation. However, the presence of fear avoidance beliefs might negatively influence PA. The objectives of this study were to investigate the relationship between fear avoidance beliefs and PA and to compare PA levels between individuals with UVP in an acute/subacute vs chronic phase.

Treatments for RYR1-related disorders.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To analyse the benefits and harms of pharmacological or other interventions (e.g.