A5001555381- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- Platelet Disorders and Treatments
- Inflammation biomarkers and pathways
- Intensive Care Unit Cognitive Disorders
- Respiratory Support and Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Nosocomial Infections in ICU
- Erythrocyte Function and Pathophysiology
- Blood disorders and treatments
- T-cell and B-cell Immunology
- Neonatal Respiratory Health Research
- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Tuberculosis Research and Epidemiology
- Immune cells in cancer
- Pneumocystis jirovecii pneumonia detection and treatment
- Atherosclerosis and Cardiovascular Diseases
- Venous Thromboembolism Diagnosis and Management
- Blood groups and transfusion
- Cellular transport and secretion
- Gut microbiota and health
University of Amsterdam
2015-2025
Sanquin
2017-2025
Amsterdam University Medical Centers
2018-2025
Leiden University Medical Center
2023-2024
Amsterdam UMC Location University of Amsterdam
2012-2021
Maastricht University
2021
University Medical Center Utrecht
2021
Molecular Oncology (United States)
2021
Institute of Infection and Immunity
2010-2020
University of Glasgow
2017
Recent studies have revealed that, in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of bacteria critical illness is unknown.
<h3>Rationale</h3> We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and the thereby identified biological phenotypes are associated mortality. <h3>Methods</h3> Consecutive ARDS were included in this prospective observational cohort study. Cluster analysis 20 inflammation, coagulation endothelial activation provided a training cohort, not taking any outcome data into account. Logistic regression...
Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment.To characterize the blood genomic response in patients with suspected CAP identify candidate biomarker rapid diagnosis on ICU admission.The study comprised two cohorts consecutively enrolled treated admission. Patients were designated (cases) no-CAP...
The heterogeneity in sepsis is held responsible, part, for the lack of precision treatment. Many attempts to identify subtypes patients those with shared underlying biology or outcomes. To date, though, there has been limited effort determine overlap across these previously identified subtypes. We aimed concordance critically ill classified by four described subtype strategies.
To investigate whether admission hyperglycemia is associated with the presentation and/or outcome of sepsis, what influence on key host responses to and differentially affects patients diabetes mellitus.A substudy a prospective observational cohort study was conducted in intensive care two tertiary hospitals between January 2011 July 2013.Of all consecutive critically ill sepsis patients, glucose used stratify euglycemia (71-140 mg/dL), mild (141-199 severe (≥ 200 hypoglycemia were excluded....
Background: Sepsis is frequently complicated by the release of cardiac troponin, but clinical significance this myocardial injury remains unclear. We studied associations between troponin during sepsis and 1-year outcomes. Methods Results: enrolled consecutive patients with in 2 Dutch intensive care units 2011 2013. Subjects a clinically apparent cause were excluded. High-sensitivity I (hs-cTnI) concentration plasma was measured daily first 4 unit days, multivariable Cox regression analysis...
Human neutrophilic granulocytes form the largest pool of innate immune cells for host defense against bacterial and fungal pathogens. The dynamic changes that accompany metamorphosis from a proliferating myeloid progenitor cell in bone marrow into mature non-dividing polymorphonuclear blood have remained poorly defined. Using mass spectrometry-based quantitative proteomics combined with transcriptomic data, we report on five developmental stages blood. Integration transcriptomes proteome...
Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these their could be extended to other patients the ICU, irrespective of fulfilling definition ARDS. Methods: This is a secondary analysis prospective observational study adult admitted ICU. We tested both cluster-derived latent-class (LCA)-derived ARDS by evaluating...
Rationale: Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a infection while in intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses.Objectives: To compare systemic proinflammatory host responses who acquire new those do not.Methods: Consecutive length of ICU stay greater than 48 hours were prospectively analyzed for development ICU-acquired Twenty response biomarkers reflective key...
Hypothermia is associated with adverse outcome in patients sepsis. The objective of this study was to characterize the host immune response hypothermic sepsis order determine if an excessive anti-inflammatory could explain immunosuppression and outcome. Markers endothelial activation integrity were also measured explore potential alternative mechanisms hypothermia. Finally we studied risk factors for hypothermia attempt find new clues etiology Consecutive diagnosed within 24 hours after...
The complex biology of asthma compels the use more relevant human allergens, such as house dust mite (HDM), to improve translation animal models into asthma. LPS exposure is associated with aggravations asthma, but mechanisms remain unclear. Here, we studied effects increasing doses on HDM-evoked allergic lung inflammation. To this end, mice were intranasally sensitized and challenged HDM or without (0.001-10 μg). dose-dependently inhibited HDM-induced eosinophil recruitment lungs mucus...
Key Points During a systemic inflammatory response, cell-free DNA is first released by hematopoietic cells and thereafter nonhematopoietic cells.
The extent of non-coding RNA alterations in patients with sepsis and their relationship to clinical characteristics, soluble mediators the host response infection, as well an advocated vivo model acute systemic inflammation is unknown. Here we obtained whole blood from 156 82 healthy subjects among whom eight were challenged lipopolysaccharide a clinically controlled setting (human endotoxemia). Via next-generation microarray analysis leukocyte found that long and, lesser extent, small...
There is limited knowledge on how the source of infection impacts host response to sepsis. We aimed compare in sepsis patients with a single, known at admission (< 24 h) intensive care unit.From molecular diagnosis and risk stratification (MARS) prospective cohort, we measured 16 plasma biomarkers reflective key pathways 621 patients. In subgroup (n = 335), blood leukocyte transcriptomes were compared between sources. Differences clinical patient profiles survival whole cohort 2019).The...
The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence age host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological domains like endothelial cell activation and function, coagulation activation. primary objective this study was gain insight into in key pathways blood transcriptomes sepsis.We analysed clinical outcome (n = 1952), 16 biomarkers providing...
In this study, the relative roles of Toll-like receptor (TLR)2 and TLR4 were investigated independently together. Moreover, we studied role haematopoietic compartment in anti- Klebsiella host defence. We infected TLR2 single-, TLR2×4 double knockout (KO) animals with different doses pneumoniae . addition, bone marrow chimeric mice created infected. played a more prominent antibacterial defence than TLR2, considering that only KO demonstrated enhanced bacterial growth lungs spleen 24 h after...
Preclinical studies suggest that hospitalized patients are susceptible to infections caused by nosocomial respiratory pathogens at least in part because of immune suppression the condition for which they were admitted.We aimed characterize systemic host response hospital-acquired pneumonia (HAP) when compared with community-acquired (CAP).We performed a prospective study two intensive care units (ICUs) 453 HAP (n = 222) or CAP 231). Immune responses determined on ICU admission measuring 19...
Diabetes is associated with chronic inflammation and activation of the vascular endothelium coagulation system, which in a more acute manner are also observed sepsis. Insulin metformin exert immune modulatory effects. In this study, we aimed to determine association diabetes preadmission insulin use sepsis outcome host response. We evaluated 1104 patients sepsis, admitted intensive care unit stratified according presence or absence mellitus. The response was examined by targeted approach (by...
Streptococcus (S.) pneumoniae is a common Gram-positive pathogen in community-acquired pneumonia and sepsis. Triggering receptor expressed on myeloid cells-1 (TREM-1) phagocytes known to amplify inflammatory responses. Previous studies showed that TREM-1 inhibition protects against lethality during experimental Gram-negative We here aimed investigate the role of an model pneumococcal pneumonia, using TREM-1/3-deficient (Trem-1/3(-/-) ) wild-type (Wt) mice. Additionally ex vivo responsiveness...
Objective: To determine the association of gender with presentation, outcome, and host response in critically ill patients sepsis. Design Setting: A prospective observational cohort study ICU two tertiary hospitals between January 2011 2014. Patients: All consecutive admitted sepsis, involving 1,815 admissions (1,533 patients). Interventions: The was evaluated on admission by measuring 19 plasma biomarkers reflecting organ systems implicated sepsis pathogenesis (1,205 admissions) applying...
Rationale: Myocardial injury, as reflected by elevated cardiac troponin levels in plasma, is common patients with community-acquired pneumonia (CAP), but its temporal dynamics and etiology remain unknown.Objectives: Our aim was to determine the incidence of release CAP identify risk factors that may point underlying etiologic mechanisms.Methods: We included consecutive admitted severe two intensive care units Netherlands between 2011 2015. High-sensitivity I measured daily during first week....
Abstract MYD88 is the key signaling adaptor-protein for Toll-like and interleukin-1 receptors. A somatic L265P mutation within Toll/interleukin-1 receptor (TIR) domain of found in 90% Waldenström macroglobulinemia cases a significant subset diffuse large B-cell lymphomas. MYD88-L265P strongly promotes NF-κB pathway activation, JAK-STAT lymphoma cell survival. Previous studies have identified other residues TIR-domain crucially involved including serine 257 (S257), indicating potentially...