Raphaël Duivenvoorden

Raphaël Duivenvoorden
Radboud University Medical Centre (Radboudumc)

MD, PhD

About

94
Publications
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Introduction

Publications

Publications (94)
Article
BACKGROUND AND AIMS Patients on kidney replacement therapy (KRT) are at a particularly high risk of mortality from COVID-19. In this study, we investigated COVID-19 mortality in KRT patients in the first and second waves of the pandemic and potential reasons for any difference in mortality between the two waves. METHOD Data from the European Renal...
Article
BACKGROUND AND AIMS during the COVID-19 pandemic, several guidelines have recommended the use of the Clinical Frailty Scale (CFS) for triage of critically ill patients with COVID-19 in case of shortage in ICU resources. However, no data on using CFS assessment for ICU triage for dialysis patients is yet available. This study evaluates whether CFS i...
Article
BACKGROUND AND AIMS In the general population with COVID-19, male sex is an established risk factor for mortality. A more robust immune response to COVID-19 in women has been suggested to be one of the factors explaining this sex difference in mortality. Patients on kidney function replacement therapy (KFRT) have an impaired immune response, especi...
Article
Background COVID-19-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients three months after their COVID-19 diagnosis. Methods We analyzed data on dialysis patients diagnosed with COVID-19 from February 1st, 2020-March 3...
Article
Background: Prolonged SARS-CoV-2 shedding has been described in immunocompromised COVID-19 patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable. Methods: Five critically ill COVID-19 patients with severe defects in cellular immune r...
Article
Background: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in patients with COVID-19. Patients with kidney failure, who often use ACEi/ARB, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/AR...
Article
The innate immune system plays a key role in atherosclerosis progression and the pathogenesis of cardiovascular disease. Trained immunity, an epigenetically regulated hyperresponsive state of myeloid cells, is a driving force underlying chronic inflammation in atherosclerosis. Therapeutically targeting innate trained immunity therefore may mature i...
Article
Macrophages play a central role in the pathogenesis of atherosclerosis. The inflammatory properties of these cells are dictated by their metabolism, of which the mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator. Using myeloid cell–specific nanobiologics in apolipoprotein E–deficient ( Apoe −/− ) mice, we found that target...
Article
Full-text available
Reported outcomes, such as incidence rates of mortality and intensive care unit admission, vary widely across epidemiological COVID-19 studies, also in the nephrology field. This variation can in part be explained by differences in patient characteristics, but also methodological aspects must be considered. In this review, we reflect on the methodo...
Article
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Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or a...
Article
Full-text available
Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specif...
Article
Full-text available
Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, sugges...
Article
Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the...
Article
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Reports suggest a role of endothelial dysfunction and loss of endothelial barrier function in COVID-19. It is well established that the endothelial glycocalyx-degrading enzyme heparanase contributes to vascular leakage and inflammation. Low molecular weight heparins (LMWH) serve as an inhibitor of heparanase. We hypothesize that heparanase contribu...
Preprint
Full-text available
Background: Several reports suggest endothelial dysfunction and loss of endothelial barrier function in COVID-19. It is well established that the endothelial glycocalyx-degrading enzyme heparanase (HPSE) contributes to vascular leakage and inflammation. Low molecular weight heparins (LMWH) serve as an inhibitor of heparanase. We hypothesize that he...
Preprint
Full-text available
SARS-CoV-2 infection can cause severe disease for which currently no specific therapy is available. The use of hydroxychloroquine to prevent or treat SARS-CoV-2 infection is controversial and its mode of action poorly understood. We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompani...
Article
Full-text available
Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (19F-HDL) to allow myeloi...
Article
Nanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse...
Chapter
Diabetes is associated with the development of various comorbidities, including retinopathy, neuropathy, nephropathy, and cardiovascular disease. The risk of macrovascular complications, such as myocardial infarction and stroke, is increased two- to threefolds when compared to nondiabetics. The increased risk is conferred by accelerated atheroscler...
Article
Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Using an experimental transplantation mouse model, we demonstrate that local macrophage activation through dectin-1 and toll-like receptor 4 (TLR4) drives trained immunity-associated cytokine production during allograft rejection. We conduc...
Article
Atherosclerosis is a chronic disease of the large arteries and the underlying cause of myocardial infarction and stroke. Atherosclerosis is driven by cholesterol accumulation and subsequent inflammation in the vessel wall. Despite the clinical successes of lipid-lowering treatments, atherosclerosis remains one of the major threats to human health w...
Article
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In the version of this Article originally published, the surname of the author Edward A. Fisher was spelt incorrectly as ‘Fischer’. This has now been corrected.
Article
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Macrophage accumulation in atherosclerosis is directly linked to the destabilization and rupture of plaque, causing acute atherothrombotic events. Circulating monocytes enter the plaque and differentiate into macrophages, where they are activated by CD4⁺ T lymphocytes through CD40–CD40 ligand signalling. Here, we report the development and multipar...
Article
Background: Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression. The authors recently identified small molecule inhibitors that block the interaction between CD40 and tumor necrosis factor receptor-associated factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, there...
Article
Aim: Circulating monocytes infiltrate the plaque and differentiate into macrophages, contributing to an inflammatory environment which is associated with higher risk of cardiovascular events. Although the pivotal role of circulating monocytes in plaque inflammation has been firmly established, the search continues to identify specific monocyte sub...
Article
Full-text available
Purpose To study the interscan reproducibility of manual versus automated segmentation of carotid artery plaque components, and the agreement between both methods, in high and lower quality MRI scans. Methods 24 patients with 30–70% carotid artery stenosis were planned for 3T carotid MRI, followed by a rescan within 1 month. A multicontrast protoc...
Data
MRI scan acquisition parameters. (DOCX)
Article
CKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts fut...
Article
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Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and...
Article
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A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stab...
Article
Objectives: The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities. Background: HDL is a natural nanoparticle that interacts with atherosclerotic plaque macroph...
Article
Full-text available
Background and aims: Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HD...
Data
Supplementary Figures 1-9, Supplementary Tables 1-3, Supplementary Discussion, Supplementary Methods and Supplementary References
Article
Objectives: We describe a 62-year-old woman with a 15-year history of a plasma cell dyscrasia (monoclonal IgGκ), manifested by type I cryoglobulinemia and dermal vasculitis. Methods: In addition to the clinical examinations, light microscopy with immunohistochemistry, sequential multicolor immunohistochemistry, and electron microscopy were used...
Article
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Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imag...
Article
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Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and...
Article
Endothelial shear stress (ESS) dynamics are a major determinant of atherosclerosis development. The frequently used Poiseuille method to estimate ESS dynamics has important limitations. Therefore, we investigated whether Womersley flow may provide a better alternative for estimation of ESS while requiring equally simple hemodynamic parameters. Comm...
Article
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Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins t...
Article
This study hypothesized that (1)H magnetic resonance spectroscopy ((1)H-MRS) can identify carotid plaque cholesteryl ester in vivo in humans. Liquid phase cholesteryl ester comprises a major fraction of atherosclerotic plaque, and its abundance is associated with plaque rupture and atherothrombosis. A noninvasive imaging technique to detect liquid...
Article
This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic even...
Article
To improve carotid 3T magnetic resonance imaging (MRI) dimension measurements in patients with overt atherosclerotic carotid artery disease. In 31 patients with advanced atherosclerotic carotid artery disease, two high resolution (0.25 × 0.25 mm(2); HR) and two routinely used low resolution (0.50 × 0.50 mm(2); LR) carotid 3T MRI scans were performe...
Article
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AimsLow HDL-C is a potent risk factor for cardiovascular disease (CVD). Yet, mutations in ABCA1, a major determinant of circulating HDL-C levels, were previously not associated with CVD risk in cohort studies. To study the consequences of low plasma levels of high-density lipoprotein cholesterol (HDL-C) due to ATP-binding cassette transporter A1 (A...
Article
Objective: Carriers of a functional mutation in LCAT, encoding lecithin:cholesterol acyl transferase, are exposed to lifelong low high-density lipoprotein cholesterol (HDL-c) levels. We investigated whether LCAT mutation carriers have increased arterial stiffness as a marker of cardiovascular disease and whether arterial stiffness was associated w...
Article
Purpose of review: Cholesteryl ester transfer protein (CETP)-inhibiting drugs effectively raise HDL cholesterol. In 2007, the CETP inhibitor torcetrapib unexpectedly showed increased fatality and cardiovascular events, possibly related to increased blood pressure and aldosterone levels caused by torcetrapib. Since then, novel CETP inhibiting drugs...
Presentation
Full-text available
Novel Regulators and Inhibitors of Aortic Valve Calcification –ESC-Congress 2012 ,Munich ,Germany
Article
The aim of this study was to investigate the role of reduced lecithin: cholesterol acyltransferase (LCAT) function on atherogenesis using 3.0-T carotid magnetic resonance imaging (MRI) and B-mode ultrasound. The role of low high-density lipoprotein cholesterol as a causal factor in atherogenesis has recently been questioned. LCAT plays a key role i...
Article
We investigated the prevalence and clinical risk factors of carotid vessel wall inflammation by means of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in a population consisting of coronary artery disease (CAD) patients. The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the arte...
Article
Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness (CIMT), to assess if we could confirm this atherosclerotic con...
Article
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Decreased level of high density-lipoprotein cholesterol (HDL-C) is a rigorous predictor for future cardiovascular events. Much effort is being made to develop HDL-C-raising pharmacotherapies in the attempt to avert the pandemic of atherosclerotic disease. Important properties by which HDL-C-raising compounds are effective involve improvement of cho...
Chapter
Magnetic resonance imaging (MRI) of the arterial wall yields a surrogate marker for atherosclerosis, which can provide an early indication of cardiovascular disease risk and enables assessing the efficacy of novel cardiovascular drugs.
Article
Full-text available
Dalcetrapib increases high-density lipoprotein cholesterol (HDL-C) levels through effects on cholesteryl ester transfer protein (CETP). As part of the dalcetrapib dal-HEART clinical trial programme, the efficacy and safety of dalcetrapib is assessed in coronary heart disease (CHD) patients in the dal-VESSEL study (ClinicalTrials.gov identifier: NCT...
Article
Accurate early diagnosis of acute coronary syndrome (ACS) is a challenging clinical problem. Imaging myocardial fatty acid metabolism with β-methyl-p-[123I]-iodophenyl-pentadecanoic acid single-photon emission computed tomography was shown to improve the accuracy of ACS diagnosis in patients presenting with chest pain and might be a valuable techni...
Article
Low endothelial shear stress (ESS) elicits endothelial dysfunction. However, the relationship between ESS and arterial remodeling and arterial stiffness is unknown in humans. We developed a 3.0-T MRI protocol to evaluate the contribution of ESS to arterial remodeling and stiffness. Fifteen young (aged 26 ± 3 years) and 15 older (aged 57 ± 3 years)...
Article
Current ultrasound protocols to measure carotid intima-media thickness (CIMT) in trials rather differ. The ideal protocol combines high reproducibility with a high precision in the measurement of the rate of change in CIMT over time and with a precise estimate of a treatment effect. To study these aspects, a post-hoc analysis was performed using da...
Article
Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess...
Article
Full-text available
Ultrasound protocols to measure carotid intima media thickness (CIMT) differ considerably with regard to the inclusion of the number of carotid segments and angles used. Detailed information on the completeness of CIMT information is often lacking in published reports, and at most, overall percentages are presented. We therefore decided to study th...