Personalized Antifibrotic Therapy in CKD Progression.

Chronic kidney disease (CKD) is a chronic disorder characterized by kidney fibrosis and extracellular matrix accumulation that can lead to end-stage kidney disease. Epithelial-to-mesenchymal transition, inflammatory cytokines, the TGF-β pathway, Wnt/β-catenin signaling, the Notch pathway, and the NF-κB pathway all play crucial roles in the progression of fibrosis. Current medications, such as renin-angiotensin-aldosterone system inhibitors, try to delay disease development but do not stop or reverse fibrosis.

Delayed Diagnosis of Disseminated Invasive Aspergillosis with Purulent Myocarditis in an Immunocompromised Host.

Invasive aspergillosis (IA) is an opportunistic fungal infection that typically occurs in the immunocompromised host and is associated with severe morbidity and mortality. Myocardial abscess formation is seldomly described. We present a case of IA with purulent myocarditis.

Absenteeism and Productivity Loss Due to Influenza or Influenza-like Illness in Adults in Europe and North America.

Healthy working-age adults are susceptible to illness or caregiving requirements resulting from annual seasonal influenza, leading to considerable societal and economic impacts. The objective of this targeted narrative review is to understand the societal burden of influenza in terms of absenteeism and productivity loss, based on the current literature. This review includes 48 studies on the impact of influenza and influenza-like illness (ILI) and reports on the effect of influenza vaccination, age, disease severity, caring for others, comorbidities, and antiviral prophylaxis on absenteeism and productivity loss due to influenza/ILI, focusing on publications originating from Canada, Europe, and the United States.

Indications for the use of dermal substitutes in patients with acute burns and in reconstructive surgery after burns: A systematic review.

Deep dermal and full-thickness burns often result in scar sequelae such as contractures, hypertrophy, pain and itching following split-thickness skin grafting. Dermal substitutes are currently employed alongside split-thickness skin grafting to enhance clinical outcomes, though their indications remain a subject of ongoing debate. This systematic review aims to clarify the indications for the application of dermal substitutes in burn patients, in both acute and reconstructive settings.

Implementing Findable, Accessible, Interoperable, Reusable (FAIR) Principles in Child and Adolescent Mental Health Research: Mixed Methods Approach.

Background: The FAIR (Findable, Accessible, Interoperable, Reusable) data principles are a guideline to improve the reusability of data. However, properly implementing these principles is challenging due to a wide range of barriers.

Objectives: To further the field of FAIR data, this study aimed to systematically identify barriers regarding implementing the FAIR principles in the area of child and adolescent mental health research, define the most challenging barriers, and provide recommendations for these barriers.

Rapid non-invasive measurement of mitochondrial oxygen tension after microneedle pre-treatment: a feasibility study in human volunteers.

Mitochondrial oxygen tension (MitoPO2) is a promising novel non-invasive bedside marker of circulatory shock and is associated with organ failure. The measurement of mitoPO2 requires the topical application of 5-aminolevulinc acid (ALA) to induce sufficient concentrations of the fluorescent protein protoporphyrin-IX within (epi)dermal cells. Currently, its clinical potential in guiding resuscitation therapies is limited by the long induction time prior to obtaining a reliable measurement signal.

The transcriptional profile of iron deficiency in patients with heart failure: Heme-sparing and reduced immune processes.

Aims: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) and associated with morbidity and poor prognosis, but pathophysiological mechanisms are unknown. We aimed to identify novel biological pathways affected by ID.

Methods And Results: We studied 881 patients with HF from the BIOSTAT-CHF cohort.

Empagliflozin in acute myocardial infarction in patients with and without type 2 diabetes: A pre-specified analysis of the EMPACT-MI trial.

Aims: In the EMPACT-MI trial, empagliflozin reduced heart failure (HF) hospitalizations but not mortality in acute myocardial infarction (MI). Contemporary reports of clinical event rates with and without type 2 diabetes mellitus (T2DM) in acute MI trials are sparse. The treatment effect of empagliflozin in those with and without T2DM in acute MI is unknown.

Imaging-Based Quantitative Assessment of Biomolecular Condensates in vitro and in Cells.

The formation of biomolecular condensates contributes to intracellular compartmentalization, and plays an important role in many cellular processes. The characterization of condensates is however challenging, requiring advanced biophysical or biochemical methods that are often less suitable for in vivo studies. A particular need for easily accessible yet thorough methods that enable the characterization of condensates across different experimental systems thus remains.

Decellularization of human iliac artery: A vascular scaffold for peripheral repairs with human mesenchymal cells.

This work presents strong evidence supporting the use of decellularized human iliac arteries combined with adipose tissue-derived stem cells (hASCs) as a promising alternative for vascular tissue engineering, opening the path to future treatments for peripheral artery disease (PAD). PAD is a progressive condition with high rates of amputation and mortality due to ischemic damage and limited graft options. Traditional synthetic grafts often fail due to poor integration, while autologous grafts may be unsuitable for patients with compromised vascular health.

Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk tools.

Background: Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.

The Many Faces of Good Operating Room Supervision: Supervisors' and Residents' Perspectives After Operating Together.

Objective: Effective operating room (OR) learning requires surgical and surgical-educational skills. Current insights into educational skills of surgical educators are derived from general perceptions of supervisors and residents via survey and interview studies. This study aims to provide insight into what educators and residents perceive as good OR supervision behavior based on actual day-to-day collaboration.

Challenges in Describing Tremor and Dystonia.

Tremor is defined as an oscillatory and rhythmical movement. By contrast, dystonia is defined by sustained or intermittent abnormal postures, repetitive movements, or both. Tremor and dystonia often coexist in the same individual.

Optimization and analytical validation of the Allplex HPV28 genotyping assay for use in first-void urine samples.

Despite first-void urine (FVU) being increasingly recognized as a credible specimen for human papillomavirus (HPV) detection, there is a lack of well-validated testing methods providing full quantitative genotyping required for vaccine impact monitoring from FVU samples. The Allplex HPV28 assay, capable of individually detecting 28 HPV genotypes, presents a promising method. We aimed to evaluate its genotype-specific performance on FVU samples, following optimization of FVU preanalytics.

Genotype-Guided Asthma Treatment Reduces Exacerbations in Children: Meta-Analysis of Two RCTs.

Background: Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment.

Development of the Dutch translational knowledge agenda for inherited metabolic diseases.

Background: Inherited metabolic diseases (IMDs) may have considerable implications for patients and their families. Despite their individual rarity, covering a spectrum of over 1800 distinct diseases, the diseases collectively exert a significant impact, with often lifelong disabilities. The United for Metabolic Diseases consortium was established to catalyze research with translation into the best possible care.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Lost and found: dynamics of relationship and employment status over time in people with affective and psychotic spectrum disorders.

Background: Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.

Aims: We investigated employment and relationship status changes among patients across the affective and psychotic spectrum - in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.

Lower risk of revision in fixed-bearing compared to mobile-bearing total ankle arthroplasties: A register based evaluation of 1246 patients in the Netherlands.

Background: Total ankle arthroplasty (TAA) has been developed as treatment for disabling tibiotalar osteoarthritis. TAAs are divided into mobile- and fixed-bearings. The aim was to determine the incidence and trends of fixed- and mobile bearings over time and investigate the association of bearing type and risk of revision after primary TAA in the Netherlands.

Does a Restrictive Diagnostic Work-up for Thyroid Nodules Lead to a Different Papillary Thyroid Cancer Patient Population? A Comparison Between Dutch and U.S. T1-T3 Patient Population.

Introduction: The 2015 American Thyroid Association guidelines recommend de-escalating surgical treatment for papillary thyroid cancer (PTC). We hypothesize that the Dutch PTC population might differ due to a restrictive diagnostic policy that mainly selects symptomatic and palpable thyroid nodules for further diagnostics, potentially selecting relatively more aggressive tumors. We aimed to describe the Dutch PTC population because differences in populations can have consequences for the adoption of foreign guidelines.

Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.

Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce.

Genomic structural equation modeling of reward-related traits: exploring the genetic factor structure and its relationship with psychopathology.

Reward sensitivity has a partial genetic background, and extreme levels may increase vulnerability to psychopathology. This study explores the genetic factor structure underlying reward-related traits and examines how genetic variance links to psychopathology. We modeled GWAS data from ten reward-related traits: risk tolerance (N = 975,353), extraversion (N = 122,886), sensation seeking (N = 132,395), (lack of) premeditation (N = 132,667), (lack of) perseverance (N = 133,517), positive urgency (N = 132,132), negative urgency (N = 132,559), attentional impulsivity (N = 124,739), motor impulsivity (N = 124,104), and nonplanning impulsivity (N = 123,509) to derive their genetic factor structure.

Multiple Sclerosis: Glial Cell Diversity in Time and Space.

Multiple sclerosis (MS) is the most prevalent human inflammatory disease of the central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease-associated glial subtypes.