Publications by authors named "Martijn Bakker"

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

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Objectives: Parainfluenza virus type 3 (PIV3) outbreaks among hematology patients are associated with high morbidity and mortality. Prompt implementation of infection prevention (IP) measures has proven to be the most efficacious approach for controlling PIV3 outbreaks within this patient population. The most suitable IP measures can vary depending on the mode of virus transmission, which remains unidentified in most outbreaks.

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We describe a unique case of a 43-year-old-female with a Bordetella bronchiseptica infection caused by zoonotic transmission following vaccination of her dog. With this report, we want to raise awareness of potential zoonotic transmission of live attenuated vaccines from animals to patients with impaired immunity.

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Many medicines are used "off-label" in children outside the terms of the license. Feasible pediatric clinical trials are a challenge to design. Conect4children (c4c) is an Innovative Medicines Initiative project to set up a pan-European pediatric clinical trial network aiming to facilitate the development of new medicines for children.

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Article Synopsis
  • The study aimed to evaluate the effectiveness of a therapeutic drug monitoring (TDM) program for ganciclovir in transplant patients due to issues like toxicity and resistance.
  • The observational study included 95 transplant patients and monitored 450 serum concentrations, highlighting significant variability in drug levels among individuals.
  • Results showed that standard dosing led to both under- and over-exposure, particularly in patients with varying kidney functions, indicating the need for further research on concentration-guided dosing adjustments.
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Background: Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications.

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Objectives: Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy.

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Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets.

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The rate of contraction of the heart relies on proper development and function of the sinoatrial node, which consists of a small heterogeneous cell population, including Tbx3 pacemaker cells. Here, we have isolated and characterized the Tbx3 cells from knock-in mice. We studied electrophysiological parameters during development and found that Venus-labeled cells are genuine Tbx3 pacemaker cells.

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This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. The first patient is diagnosed with thymoma A, the second is a heart transplant recipient, and the third is an HIV-positive patient. These patients were all diagnosed with cytomegalovirus and treated with ganciclovir.

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During inflammation, several cytochrome P450 enzymes are downregulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is metabolised only to a limited extent by cytochrome P450 enzymes and to a wider extent by phase 2 enzyme systems.

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Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole.

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Selective functionalization of white phosphorus is achieved by addition of ArLi to unique cationic coinage metal η(2)-P4 complexes. This novel approach allows controlled P-C bond formation using the bulky DmpLi (Dmp = 2,6-Mes2C6H3) and the unencumbered MesLi, giving sterically diverse doubly complexed RP4 butterfly derivatives in a single step.

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A simple and efficient methodology is presented for the synthesis of a wide range of substituted imines. It is based on stabilizing readily available, but thermally labile, N-alkylnitrilium triflates with pyridine or DMAP to moderately air-stable adducts. These base-stabilized imine synthons react conveniently with phosphorus- and nitrogen-based nucleophiles to amidines and phosphaamidines.

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Article Synopsis
  • * In adult mice, Tbx3 is primarily expressed in hormone receptor-positive luminal cells, crucial for mammary epithelial identity, and its absence affects the formation of these cells.
  • * This study highlights the cell type-specific targets of Tbx3, revealing its vital role in generating hormone-sensing cells in the mammary gland.
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The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers.

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Aim: Treatment of disorders of the sinus node or the atrioventricular node requires insights into the molecular mechanisms of development and homoeostasis of these pacemaker tissues. In the developing heart, transcription factor TBX3 is required for pacemaker and conduction system development. Here, we explore the role of TBX3 in the adult heart and investigate whether TBX3 is able to reprogramme terminally differentiated working cardiomyocytes into pacemaker cells.

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TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood.

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The sinus node generates the electrical impulse, which spreads rapidly over both atria, causing them to contract simultaneously. In the normal heart, a layer of connective tissue electrically insulates the atria and ventricles. The only pathway that crosses this plane is the atrioventricular conduction axis, through which the impulse reaches the ventricles.

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Disorders of the cardiac conduction system occur frequently and may cause life-threatening arrhythmias requiring medication or electronic pacemaker implantation. Repair or regeneration of conduction system components is currently not possible due to limited knowledge of the molecular regulation of pacemaker myocardium. Origin and development of the cardiac conduction system have been subject to debate for many decades.

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The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the developing AV node.

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