A5003744221- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Mast cells and histamine
- Acute Myeloid Leukemia Research
- Eosinophilic Disorders and Syndromes
- Asthma and respiratory diseases
- Hematopoietic Stem Cell Transplantation
- Neutropenia and Cancer Infections
- Legionella and Acanthamoeba research
- Pneumocystis jirovecii pneumonia detection and treatment
- Urticaria and Related Conditions
- Chronic Lymphocytic Leukemia Research
- Infectious Diseases and Mycology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- Antimicrobial Resistance in Staphylococcus
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Dermatology and Skin Diseases
- Ocular Infections and Treatments
- Allergic Rhinitis and Sensitization
- Sepsis Diagnosis and Treatment
- Autoimmune Bullous Skin Diseases
- Bacterial Identification and Susceptibility Testing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parasitic Diseases Research and Treatment
University Medical Center Groningen
2014-2024
University of Groningen
2014-2024
Pfizer (United Kingdom)
2016
Palmetto Hematology Oncology
2015
Maastricht University Medical Centre
2007-2010
University Medical Center Utrecht
2009-2010
Radboud University Nijmegen
1992-2007
Radboud University Medical Center
2001-2007
University Medical Center
2001
Presbyterian St. Luke's Medical Center
1997-1998
Abstract Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of prespecified interim analysis an ongoing pivotal single-arm phase 2 trial (no. NCT03580655 ) avapritinib, potent, selective D816V inhibitor administered primarily at once-daily starting dose 200 mg in patients with AdvSM ( n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints...
During an infection or inflammation, several drug-metabolizing enzymes in the liver are down-regulated, including cytochrome P450 iso-enzymes. Since voriconazole is extensively metabolized by iso-enzymes, metabolism of can be influenced during inflammation via reduced clearance drug, resulting higher trough concentrations.To investigate prospectively influence on and concentrations.A prospective observational study was performed at University Medical Center Groningen. Patients were eligible...
In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius® multiplex real-time PCR assay identifies clinically relevant Aspergillus species and four resistance-associated mutations (RAMs; TR34/L98H/T289A/Y121F) in the Cyp51A gene. This multicentre study evaluated diagnostic performance of this on bronchoalveolar lavage (BAL) fluid correlated presence RAMs treatment failure mortality. Stored BAL...
Abstract Background Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. Methods In prospective study, we evaluated the clinical value AsperGenius polymerase chain reaction (PCR) assay hematology patients from 12 centers. This PCR detects most frequent cyp51A mutations A. conferring azole resistance. Patients were included when computed tomography...
ABSTRACT Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored correlation between inflammation, reflected C-reactive protein (CRP) concentrations, voriconazole trough concentrations. A retrospective chart review patients with at least one steady-state concentration CRP measured on...
Voriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment superior standard for invasive aspergillosis. A multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole. All received dose at the start of treatment. Blood/serum/plasma periodically collected...
Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response patients under VCZ medication might also influence this fluctuation concentrations. In study, we explored the association between inflammation, reflected C-reactive protein (CRP) concentration, trough...
ABSTRACT Invasive aspergillosis and candidemia are important causes of morbidity mortality in immunocompromised critically ill patients. The triazoles voriconazole, fluconazole, posaconazole widely used for the treatment prophylaxis these fungal infections. Due to variability pharmacokinetics among within individual patients, therapeutic drug monitoring is optimizing efficacy safety antifungal treatment. A dried blood spot (DBS) analysis was developed clinically validated 28 Furthermore, a...
Invasive fungal infections (IFIs) occur mostly in immunosuppressed patients and can be life-threatening. Inadequate treatment is associated with high morbidity mortality. We examined the role of 2-fluorodeoxyglucose positron emission tomography integrated CT (FDG-PET/CT) monitoring IFIs therapy decision-making, evaluated baseline metabolic parameters predicting response. All between October 2009 March 2018, diagnosed IFIs, treated antifungal drugs, who underwent FDG-PET/CT at one or more...
The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance.To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in transplant patient population.An observational study was performed recipients from June 2018 February 2020. Dose adjustments were advised the TDM pharmacist as part clinical care. For prophylaxis, trough concentration (Cmin) 1-2 mg/L an AUC24h >50 mg·h/L aimed for. treatment, Cmin 2-4 80-120...
To study the apoptotic process in time, we used following flow cytometric (FCM) techniques: phosphatidylserine (PS) translocation by Annexin-V (AnV), DNA fragmentation situ end labeling (ISEL), and propidium iodide (PI) staining. Because PS is assumed to be an early feature of programmed cell death (PCD), questioned if AnV positivity implies inevitable death.Apoptosis was induced Jurkat cells gamma-irradiation, incubation with camptothecin (CPT), or cytosine beta-D-arabinofuranoside (Ara-C)....
Voriconazole pharmacokinetics shows a large inter- and intrapatient variability. Inflammation is associated with changes in the expression of CYP isoenzymes. Here, we evaluated influence inflammation, marked by C-reactive protein (CRP) levels blood, on metabolism voriconazole. Observational data showed an association between CRP level ratio voriconazole N-oxide to
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients experience prolonged neutropenia after treatment with intensive chemotherapy, leading to a high risk of invasive fungal infections (IFI). The present study evaluates the cost effectiveness posaconazole vs. standard azoles for prevention IFIs in neutropenic Netherlands.A decision-tree model was developed using data from randomized trial that compared azole (fluconazole or itraconazole) prophylaxis receiving...
Objectives: Historically, patients with a hematologic malignancy have one of the highest mortality rates among cancer admitted to ICU. Therefore, physicians are often reluctant admit these The aim our study was examine survival who and multiple organ failure Design: This retrospective cohort study, part HEMA-ICU group, designed after admission Patients were followed for at least 1 year. Setting: Five university hospitals in Netherlands. Patients: One-thousand ninety-seven Interventions:...
Posaconazole exposure seems to be subtherapeutic in some patients with invasive fungal disease. Due the pharmacokinetic variability of posaconazole, therapeutic drug monitoring may help optimize efficacy this antifungal drug.A retrospective study treated posaconazole from January 2008 April 2014 and for whom serum concentrations were available was conducted. Risk factors underexposure detected, relationship between treatment outcome according European Organization Research Treatment Cancer...
Summary Patients with haematological malignancies are at risk for invasive fungal diseases ( IFD ). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards the context of azole‐resistance. In 8 centres, a haematologist microbiologist filled questionnaire that focused different subgroups patients. Fungal prophylaxis during neutropaenia directed against Candida consisted fluconazole and/or amphotericin B...
Anatomy-based imaging methods are the usual used in assessing invasive fungal infections (IFIs). [18F]FDG PET/CT has also been evaluation of IFIs. We assessed added value when to most frequently anatomy-based studies The study was conducted two University Medical Centers Netherlands. Reports and performed within weeks scan were retrieved, presence sites IFI lesions documented for each procedure. included 155 scans 73 patients. A total 216 including 80 chest X-rays, 89 computed tomography...
The paradox of pancytopenia despite cellular bone marrows (BM) was investigated in 120 patients with myelodysplastic syndromes (MDS). Detailed cell cycle kinetics were examined following vivo infusions iodo-and/or bromodeoxyuridine (IUdR/BrdU), while the incidence apoptosis measured by situ end labeling (ISEL) fragmented DNA. Results showed that MDS are highly proliferative disorders an equally high apoptotic intramedullary death accounting for cellularity/cytopenia. By double-labeling BM...
Leukaemic patients receiving intensive chemotherapy and undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect leaving chronic untreated on development in intensively treated haematological patients. We included prospectively evaluated all leukaemic ASCT who were referred our medical centre between September 2012 May 2014,...