Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability.

Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify the underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed.

Proteomic profiling of peripheral blood mononuclear cells reveals immune dysregulation and metabolic alterations in kidney transplant recipients with COVID-19.

The COVID-19 pandemic has significantly impacted global health, especially in vulnerable populations like kidney transplant recipients (KTRs). Recently, mass spectrometry-based proteomics has emerged as a powerful tool to shed light on a broad spectrum of dysregulated biological processes in KTRs with COVID-19. In this study, we prospectively collected blood samples from 17 COVID-19-positive KTRs and 10 non-infected KTRs between May and September 2020.

The influence of the dynamic context of the pandemic on the predictive performance of mortality predictions over time in older patients hospitalised for COVID-19.

Objective: During the COVID-19 pandemic, dynamic factors such as governmental policies, improved treatment and prevention options and viral mutations changed the incidence of outcomes and possibly changed the relation between predictors and outcomes. The aim of the present study was to assess whether the dynamic context of the pandemic influenced the predictive performance of mortality predictions over time in older patients hospitalised for COVID-19.

Study Design And Setting: The COVID-OLD study, a multicentre cohort study in the Netherlands, included COVID-19 patients aged 70 years and older hospitalised during the first (early 2020), second (late 2020), third (late 2021) or fourth wave (early 2022).

Tumor gene expression is associated with venous thromboembolism in patients with ductal pancreatic adenocarcinoma.

Introduction: In patients with pancreatic cancer, the risk of venous thromboembolism (VTE) is high compared to other cancer types, suggesting that tumor-intrinsic features drive hypercoagulability. Tumor gene expression analysis may help unravel the pathogenesis of VTE in these patients and help to identify high-risk patients.

Aim: To evaluate the association between tumor gene expression patterns and VTE in patients with pancreatic cancer.

NanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.

Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.

Skeletal muscle adaptations and post-exertional malaise in long COVID.

When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms.

Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.

Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.

Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.

Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS).

Longitudinal assessment of immunoglobulin response and disease progression in critically ill patients with community acquired pneumonia.

Background: Low endogenous immunoglobulin(Ig)-levels are common in critically ill patients with sepsis, but it is unknown whether low Ig-levels are associated with poor outcome, and in which patients Ig-replacement therapy (IgRT) improves outcome. Given the crucial role of immunoglobulins in eliminating certain encapsulated pathogens, we examined the relationship between serial Ig-levels and disease course in critically ill patients with community acquired pneumonia (sCAP) caused by encapsulated or other pathogens.

Methods: We included a cohort of consecutive critically ill patients with CAP, and PaO/FiO-ratio < 200 with or without septic shock, from an existing biorepository where microbiological causes of infection had been adjudicated in a protocolized manner.

Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity.

Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals.

Association of epigenetic landscapes with heterogeneity and plasticity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes.

Limited evidence of infection with other tick-borne pathogens in patients tested for Lyme neuroborreliosis in the Netherlands.

Ixodes ricinus is the main vector of the causative agents of Lyme neuroborreliosis. This tick species can also transmit tick-borne encephalitis virus (TBEV), spotted fever group (SFG) Rickettsia and Borrelia miyamotoi to humans. These tick-borne pathogens are present in Dutch ticks and have also been associated with human neurological infections, but well characterized disease cases are seldom reported.

Identifying colorectal cancer-specific vulnerabilities in the Wnt-driven long non-coding transcriptome.

Background: Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved.

Objective: In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome and exploit essential molecules as novel therapeutic targets.

Clinical Subtype Trajectories in Sepsis Patients Admitted to the ICU: A Secondary Analysis of an Observational Study.

Objectives: Sepsis is an evolving process and proposed subtypes may change over time. We hypothesized that previously established sepsis subtypes are dynamic, prognostic of outcome, and trajectories are associated with host response alterations.

Design: A secondary analysis of two observational critically ill sepsis cohorts: the Molecular diAgnosis and Risk stratification of Sepsis (MARS) and the Medical Information Mart for Intensive Care-IV (MIMIC-IV).

Gut Microbiome in Human Melioidosis: Composition and Resistome Dynamics from Diagnosis to Discovery.

Background: Melioidosis, attributable to the soil-dwelling bacterium , stands as a paramount global health challenge, necessitating extended courses of antibiotics. While murine studies identified the gut microbiota as a modulator of bacterial dissemination during melioidosis, the human intestinal microbiota during melioidosis remains uncharacterized. Here, we characterized gut microbiota composition and antimicrobial resistance (AMR) genes at diagnosis, during treatment, and postdischarge for melioidosis.

Karyotype evolution in response to chemoradiotherapy and upon recurrence of esophageal adenocarcinomas.

The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC (low-purity inference of absolute copy-number alterations [CNAs]), a bio-informatics technique that allows inference of absolute CNAs of low-purity samples by leveraging the information of high-purity samples from the same cancer.

Proteomic profiling of neutrophils and plasma in community-acquired pneumonia reveals crucial proteins in diverse biological pathways linked to clinical outcome.

Introduction: Neutrophils play a dichotomous role in community-acquired pneumonia (CAP), providing protection and potentially causing damage. Existing research on neutrophil function in CAP relies on animal studies, leaving a gap in patient-centered investigations.

Methods: We used mass spectrometry to characterize the neutrophil proteome of moderately ill CAP patients at general ward admission and related the proteome to controls and clinical outcomes.

Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Background & Aims: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.

Methods: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies.

Quality of care after a horizontal merger between two large academic hospitals.

Background: Hospital mergers remain common, but their influence on healthcare quality varies. Data on effects of European hospital mergers are ill defined, and academic hospitals in particular. This case study assesses early quality of care changes in two formerly competing Dutch academic hospitals that merged on June 6, 2018.

Integrating Clinical Variables, Radiomics, and Tumor-derived Cell-Free DNA for Enhanced Prediction of Resectable Esophageal Adenocarcinoma Outcomes.

Purpose: The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of patients with resectable esophageal adenocarcinoma is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions.

Methods And Materials: A cohort of 111 patients with resectable esophageal adenocarcinoma from 2 centers treated with neoadjuvant chemoradiation therapy was used for exploratory retrospective analyses.

Empirical antibiotic therapy for sepsis: save the anaerobic microbiota.

Antibiotics are fundamental in sepsis management; however, the optimal empirical treatment remains debated. Despite anaerobes rarely being the causative pathogen of sepsis, antibiotics targeting them are frequently used, which might lead to unintended consequences. Multiple studies have shown that depletion of commensal anaerobic gut microbes by anti-anaerobic antibiotics influences systemic immunity and is associated with increased mortality in patients with sepsis.

Bridging the gap: Insights in the immunopathology of Lyme borreliosis.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity.

Effect of mesenchymal stem cells on the host response in severe community-acquired pneumonia.

Mesenchymal stem cells (MSC) have immune regulatory properties that may ameliorate pathophysiological processes in sepsis. We determined the effect of allogeneic adipose-derived MSCs (Cx611) on the host response during sepsis due to community-acquired bacterial pneumonia (CABP) by measuring 29 plasma biomarkers and blood transcriptomes at six time points in 82 patients randomised to two intravenous infusions of Cx611 or placebo. Cx611 treatment enhanced several endothelial cell and procoagulant response plasma biomarkers, and led to increased expression of pathways related to innate immunity, haemostasis and apoptosis.

Topical adjunctive treatment with flagellin augments pulmonary neutrophil responses and reduces bacterial dissemination in multidrug-resistant infection.

Objective: Antimicrobial resistance is an emerging problem and multi-drug resistant (MDR) () represents an enormous risk of failing therapy in hospital-acquired pneumonia. The current study aimed to determine the immunomodulatory effect of topical flagellin in addition to antibiotic treatment during respiratory infection evoked by hypervirulent antibiotic-susceptible and antibiotic-resistant in mice.

Methods: C57BL6 mice were inoculated intranasally with hypervirulent (K2:O1) which was either antibiotic-susceptible or multi-drug resistant.