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Background: Timely intervention in patients with splenic injury is essential, since delay to treatment is associated with an increased risk of mortality. Transcatheter Arterial Embolisation (TAE) is increasingly used as an adjunct to non-operative management. The aim of this study was to report time intervals between admission to the trauma room and start of intervention (TAE or splenic surgery) in patients with splenic injury. Methods: Consecutive patients with splenic injury aged ≥16 years admitted between January 2006 and January 2012 were included. Data were reported according to haemodynamic status (stable versus unstable). In haemodynamically (HD) unstable patients, transfusion requirement, intervention-related complications and the need for a re-intervention were compared between the TAE and splenic surgery group. Results: The cohort consisted of 96 adults of whom 16 were HD unstable on admission. In HD stable patients, median time to intervention was 105 (IQR 77-188) min: 117 (IQR 78-233) min for TAE compared to 95 (IQR 69-188) for splenic surgery (p = 0.58). In HD unstable patients, median time to intervention was 58 (IQR 41-99) min: 46 (IQR 27-107) min for TAE compared to 64 (IQR 45-80) min for splenic surgery (p = 0.76). The median number of transfused packed red blood cells was 8 (3-22) in HD unstable patients treated with TAE versus 24 (9-55) in the surgery group (p = 0.09). No intervention-related complications occurred in the TAE group and one in the splenic surgery group (p = 0.88). Two spleen related re-interventions were performed in the TAE group versus 3 in the splenic surgery group (p = 0.73). Conclusions: Time to intervention did not differ significantly between HD unstable patients treated with TAE and patients treated with splenic surgery. Although no difference was observed with regard to intervention-related complications and the need for a re-intervention, a trend towards lower transfusion requirement was observed in patients treated with TAE compared to patients treated with splenic surgery. We conclude that if 24/7 interventional radiology facilities are available, TAE is not associated with time loss compared to splenic surgery, even in HD unstable patients. © 2013 Elsevier Ltd. All rights reserved.


Sudden cardiac death occurs in a minority of patients in the absence of structural or functional abnormalities. In this category, pure electrical heart diseases are responsible for a large number of these unexpected deaths. These conditions include the long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome (collectively referred to as channelopathies) and idiopathic ventricular fibrillation. This article reviews the current molecular understanding of the electrical diseases of the heart associated with sudden cardiac death, and provides a summary of the causal genes and a flowchart with an overview of the genotype-phenotype correlation of the most common arrhythmia syndromes. © 2010 Future Medicine Ltd.


Li K.-Y.,Leiden Institute of Chemistry | Witte M.D.,Leiden Institute of Chemistry | Aten J.,Meibergdreef | Jiang J.,Leiden Institute of Chemistry | And 7 more authors.
Angewandte Chemie - International Edition | Year: 2012

A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well as several non-mammalian β-glucosidases (see picture). These probes offer new ways to study β-exoglucosidases, and configurational isomers of the cyclophellitol aziridine core may give activity-based probes targeting other retaining glycosidase families. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


PubMed | Center for Experimental and Molecular Medicine, Center for Experimental and Molecular Medicine Amsterdam Multidisciplinary Lyme borreliosis Center, Institute for Public Health and Environment, Meibergdreef and Public Health Service Amsterdam
Type: | Journal: Ticks and tick-borne diseases | Year: 2017

Ixodes ticks transmit Borrelia burgdorferi sensu lato (s.l.), the causative agent of Lyme borreliosis (LB). These tick species also transmit Borrelia miyamotoi, which was recently found to cause infections in humans. We were interested in the prevalence of B. miyamotoi infection in ticks and natural hosts in The Netherlands, and to what extent ticks are co-infected with B. burgdorferi. In addition, erythema migrans has been sporadically described in B. miyamotoi-infected patients, but these skin lesions might as well represent co-infections with B. burgdorferi s.l. We therefore investigated whether B. miyamotoi was present in LB-suspected skin lesions of patients referred to our tertiary Lyme disease clinic. 3360 questing Ixodes ricinus nymphs as well as spleen tissue of 74 rodents, 26 birds and 10 deer were tested by PCR for the presence of B. miyamotoi. Tick lysates were also tested for the presence of B. burgdorferi s.l. Next, we performed a PCR for B. miyamotoi in 31 biopsies from LB-suspected skin lesions in patients visiting our tertiary Lyme center. These biopsies had been initially tested for B. burgdorferi s.l. by PCR, and the skin lesions had been investigated by specialized dermatologists. Out of 3360 unfed (or questing) nymphs, 313 (9.3%) were infected with B. burgdorferi s.l., 70 (2.1%) were infected with B. miyamotoi, and 14 (0.4%) were co-infected with B. burgdorferi s.l. and B. miyamotoi. Co-infection of B. burgdorferi s.l. with B. miyamotoi occurred more often than expected from single infection prevalences (p=0.03). Both rodents (9%) and birds (8%) were found positive for B. miyamotoi by PCR, whereas the roe deer samples were negative. Out of 31 LB-suspected skin biopsies, 10 (32%) were positive for B. burgdorferi s.l. while none were positive for B. miyamotoi. The significant association of B. burgdorferi s.l. with B. miyamotoi in nymphs implies the existence of mutual reservoir hosts. Indeed, the presence of B. miyamotoi DNA indicates systemic infections in birds as well as rodents. However, their relative contributions to the enzootic cycle of B. miyamotoi requires further investigation. We could not retrospectively diagnose B. miyamotoi infection using biopsies of LB-suspected skin lesions, supporting the hypothesis that B. miyamotoi is not associated with LB-associated skin manifestations. However, this warrants further studies in larger sets of skin biopsies. A prospective study focused on acute febrile illness after a tick bite could provide insight into the incidence and clinical manifestations of B. miyamotoi infection in The Netherlands.


Alves C.H.,Meibergdreef | Sanz sanz A.,Meibergdreef | Park B.,Meibergdreef | Pellissier L.P.,Meibergdreef | And 14 more authors.
Human Molecular Genetics | Year: 2013

In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, we generated and analysed conditional knockout mice lacking CRB2 in the developing retina. Progressive disorganization was detected during late retinal development. Progressive thinning of the photoreceptor layer and sites of cellular mislocalization was detected throughout the CRB2-deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Under scotopic conditions using electroretinography, the attenuation of the a-wave was relatively stronger than that of the b-wave, suggesting progressive degeneration of photoreceptors in adult animals. Histological analysis of newborn mice showed abnormal lamination of immature rod photoreceptors and disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells. The number of late-born progenitor cells, rod photoreceptors and Müller glia cells was increased, concomitant with programmed cell death of rod photoreceptors. The data suggest an essential role for CRB2 in proper lamination of the photoreceptor layer and suppression of proliferation of late-born retinal progenitor cells. © The Author 2012. Published by Oxford University Press. All rights reserved.


PubMed | AZ Electronic and Meibergdreef
Type: | Journal: Resuscitation | Year: 2016

Bradyasystolic heart rhythms are often recorded in out-of-hospital cardiac arrest (OHCA). Atrioventricular (AV) conduction disorders might lead to OHCA, but the prevalence of AV-conduction disorders and other bradyasystolic rhythms in OHCA is unknown. These patients might benefit from pre-hospital pacing. We aimed to determine the prevalence of different types of bradyasystolic heart rhythms in OHCA, including third degree AV-block, and document survival rates.We used data from the ARREST-registry of OHCA in the Netherlands. Patients with bradyasystolic OHCA in 2006-2012 were included. ECGs were classified according to the presence of P-waves and QRS complexes in five rhythm groups. Differences in survival to discharge in relation to resuscitation characteristics, rhythm and pacing were tested using Chi-Square test and multivariate regression analysis.We included 2333 patients with a bradyasystolic rhythm; 371 patients (16%) presented with a third degree AV-block. In total 45 patients (1.9%, 95%-CI 1.4-2.5%) survived. A third degree AV-block (adjusted OR 0.86, 95%-CI 0.38-1.96) or pacing (adjusted OR 0.89, 95%-CI 0.21-3.78) was not associated with survival. Pacing was initiated in 110 patients (4.7%), after a long delay (median 18.7min). The strongest association with survival was found for the presence of a bradycardia (vs. asystole) (adjusted OR 4.20, 95%-CI 1.79-9.83), bystander witnessed (OR 4.13, 95%-CI 1.45-11.8) and EMS witnessed collapse (OR 5.18, 95%-CI 2.77-9.67).In bradyasystolic OHCA, 16% of all patients present with third degree AV-block, but survival for these and other bradyasystolic patients remains poor. Pacing is seldom initiated, often delayed, and rarely beneficial.


PubMed | Catholic University of Leuven, Meibergdreef and University of Antwerp
Type: | Journal: Neuroscience | Year: 2015

We recently reported that apolipoprotein E (ApoE)-deficient mice with a mutation in the fibrillin-1 gene (ApoE(-/-)Fbn1(C1039G+/-)) develop accelerated atherosclerosis with enhanced inflammation, atherosclerotic plaque rupture, myocardial infarction and sudden death. In the brain, fibrillin-1 functions as an attachment protein in the basement membrane, providing structural support to the blood-brain barrier (BBB). Here, we investigated whether fibrillin-1 impairment affects the permeability of the BBB proper and the blood-cerebrospinal fluid barrier (BCSFB), and whether this leads to the accelerated accumulation of lipids (xanthomas) in the brain. ApoE(-/-) (n=61) and ApoE(-/-)Fbn1(C1039G+/-) (n=73) mice were fed a Western-type diet (WD). After 14 weeks WD, a significantly higher permeability of the BBB was observed in ApoE(-/-)Fbn1(C1039G+/-) mice compared to age-matched ApoE(-/-) mice. This was accompanied by leukocyte infiltration, enhanced expression of pro-inflammatory cytokines, matrix metalloproteinases and transforming growth factor-, and by decreased expression of tight junction proteins claudin-5 and occludin. After 20 weeks WD, 83% of ApoE(-/-)Fbn1(C1039G+/-) mice showed xanthomas in the brain, compared to 23% of their ApoE(-/-) littermates. Xanthomas were mainly located in fibrillin-1-rich regions, such as the choroid plexus and the neocortex. Our findings demonstrate that dysfunctional fibrillin-1 impairs BBB/BCSFB integrity, facilitating peripheral leukocyte infiltration, which further degrades the BBB/BCSFB. As a consequence, lipoproteins can enter the brain, resulting in accelerated formation of xanthomas.


Van Maldegem B.T.,Meibergdreef | Duran M.,University of Amsterdam | Wanders R.J.A.,University of Amsterdam | Waterham H.R.,University of Amsterdam | Wijburg F.A.,Meibergdreef
Pediatric Research | Year: 2010

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inborn error, biochemically characterized by increased plasma butyrylcarnitine (C4-C) concentration and increased ethylmalonic acid (EMA) excretion and caused by rare mutations and/or common gene variants in the SCAD encoding gene. Although its clinical relevance is not clear, SCADD is included in most US newborn screening programs. Riboflavin, the precursor of flavin adenine dinucleotide (FAD, cofactor), might be effective for treating SCADD. We assessed the FAD status and evaluated the effects of riboflavin treatment in a prospective open-label cohort study involving 16 patients with SCADD, subdivided into mutation/mutation (mut/mut), mutation/variant (mut/var), and variant/variant (var/var) genotype groups. Blood FAD levels were normal in all patients before therapy, but significantly lower in the mut/var and var/var groups compared with the mut/mut group. Riboflavin treatment resulted in a decrease in EMA excretion in the mut/var group and in a subjective clinical improvement in four patients from this group. However, this improvement persisted after stopping treatment. These results indicate that high-dose riboflavin treatment may improve the biochemical features of SCADD, at least in patients with a mut/var genotype and low FAD levels. As our study could not demonstrate a clinically relevant effect of riboflavin, general use of riboflavin cannot be recommended. Copyright © 2010 International Pediatric Research Foundation, Inc.


Lahrouchi N.,Meibergdreef | Bezzina C.R.,Meibergdreef
Netherlands Heart Journal | Year: 2016

Cardiac resynchronisation therapy (CRT) is an accepted treatment for heart failure patients with depressed left ventricular (LV) function and dyssynchrony. However, despite better clinical outcome and improved cardiac function after CRT in the majority of eligible heart failure patients, a large proportion of implanted patients do not seem to benefit clinically from this therapy. In this review we consider whether genetic factors may play a role in modulating response to CRT and summarise the few genetic studies that have investigated the role of genetic variation in candidate genes. © The Author(s) 2015.


Hulleman M.,Meibergdreef | Mes H.,Meibergdreef | Blom M.T.,Meibergdreef | Koster R.W.,Meibergdreef
Resuscitation | Year: 2016

Aims Bradyasystolic heart rhythms are often recorded in out-of-hospital cardiac arrest (OHCA). Atrioventricular (AV) conduction disorders might lead to OHCA, but the prevalence of AV-conduction disorders and other bradyasystolic rhythms in OHCA is unknown. These patients might benefit from pre-hospital pacing. We aimed to determine the prevalence of different types of bradyasystolic heart rhythms in OHCA, including third degree AV-block, and document survival rates. Methods We used data from the ARREST-registry of OHCA in the Netherlands. Patients with bradyasystolic OHCA in 2006–2012 were included. ECGs were classified according to the presence of P-waves and QRS complexes in five rhythm groups. Differences in survival to discharge in relation to resuscitation characteristics, rhythm and pacing were tested using Chi-Square test and multivariate regression analysis. Results We included 2333 patients with a bradyasystolic rhythm; 371 patients (16%) presented with a third degree AV-block. In total 45 patients (1.9%, 95%-CI 1.4–2.5%) survived. A third degree AV-block (adjusted OR 0.86, 95%-CI 0.38–1.96) or pacing (adjusted OR 0.89, 95%-CI 0.21–3.78) was not associated with survival. Pacing was initiated in 110 patients (4.7%), after a long delay (median 18.7 min). The strongest association with survival was found for the presence of a bradycardia (vs. asystole) (adjusted OR 4.20, 95%-CI 1.79–9.83), bystander witnessed (OR 4.13, 95%-CI 1.45–11.8) and EMS witnessed collapse (OR 5.18, 95%-CI 2.77–9.67). Conclusion In bradyasystolic OHCA, 16% of all patients present with third degree AV-block, but survival for these and other bradyasystolic patients remains poor. Pacing is seldom initiated, often delayed, and rarely beneficial. © 2016 The Author(s)

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