ErasmusMC Sophia Childrens Hospital

Rotterdam, Netherlands

ErasmusMC Sophia Childrens Hospital

Rotterdam, Netherlands
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Schmiegelow K.,Copenhagen University | Lausten Thomsen U.,Copenhagen University | Pacheco C.E.,Hospital Infantil Manuel Of Jesus Rivera | Pieters R.,ErasmusMC Sophia Childrens Hospital | And 7 more authors.
Leukemia | Year: 2012

Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N=51) or more (N=3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83±0.05. Ages at diagnosis (Spearman correlation coefficient, r S=0.41, P=0.002) were significantly correlated, but not WBCs (r S=0.23, P=0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N=3), t(12;21) [ETV6/RUNX1] (N=1), MLL rearrangement (N=1) or t(1;19)(q23/p13) (N=1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N=5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N=6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P<0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors. © 2012 Macmillan Publishers Limited All rights reserved.

Malogolowkin M.H.,Medical College of Wisconsin | Spreafico F.,Fondazione IRCCS Instituto Nazionale Tumori | Dome J.S.,Childrens National Medical Center | van Tinteren H.,Comprehensive Cancer Center | And 5 more authors.
Pediatric Blood and Cancer | Year: 2013

Background: Most relapses from Wilms' tumor occur within 2 years from diagnosis. This study aims to describe the incidence and outcome of patients who experienced a late recurrence (LR) more than 5 years after diagnosis across several clinical trials, and to develop evidence-based recommendations for follow-up surveillance. Methods: Available records on children with Wilms' tumor enrolled onto 10 national or international cooperative clinical trials were reviewed to identify patients who experienced a LR. Results: Seventy of 13,330 (0.5%) patients with Wilms' tumor experienced a LR. No gender bias was observed. Median time elapsing between initial Wilms' tumor diagnosis and first recurrence was 13.2 years (range: 5.1-17.3 years). Initial tumor stage was: stage I (15); stage II (19); stage III (14); stage IV (8); bilateral disease stage V (14). The most frequent sites of relapse were-abdomen: 21, lungs: 20, and contralateral kidney: 15. Thirty-five children died of disease progression. Recurrence in the contralateral kidney was associated with a better outcome (13/15 patients alive), while initial tumor stage did not seem to influence the post-recurrence outcome. Therapies administered at recurrence varied between centers, preventing any conclusion about the best salvage treatment. Conclusions: LR of Wilms' tumor is rare and associated with similar outcome to those experiencing earlier recurrence. The low rate of LR does not justify prolonged monitoring. Further study of the biology of these tumors may give us some insights in regards to mechanisms on tumor cell dormancy or cancer stem cell maintenance. Pediatr Blood Cancer 2013;60:1612-1615. © 2013 Wiley Periodicals, Inc.

Perdicchio M.,VU University Amsterdam | Perdicchio M.,Fred Hutchinson Cancer Research Center | Cornelissen L.A.M.,VU University Amsterdam | Streng-Ouwehand I.,VU University Amsterdam | And 7 more authors.
Oncotarget | Year: 2016

The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created "sialic acid low" tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing "sialic acid low" tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumorspecific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack.

Schell-Feith E.A.,Rijnland Ziekenhuis | Kist-Van Holthe J.E.,Leiden University | Van Der Heijden A.J.,ErasmusMC Sophia Childrens Hospital
Pediatric Nephrology | Year: 2010

The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stoneinhibiting factors. A limited number of histological studies suggest that calcium oxalate crystals play an important role in NC in premature neonates. In 85% of children resolution of NC occurs in the first years of life. Prematurity, per se, is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. In addition, NC in preterm neonates can have long-term sequelae for glomerular and tubular function. Long-term follow-up of blood pressure and renal function of prematurely born children, especially with neonatal NC, is recommended. Prevention of NC with (low) oral doses of citrate has not resulted in a significant decrease in the prevalence of NC; a higher citrate dosage deserves further study. Future research pertaining to prevention of NC in preterm neonates is crucial. © IPNA 2008.

Kuiper J.W.,mc Medical Center | Vaschetto R.,mc Medical Center | Vaschetto R.,University of Piemonte Orientale | Corte F.D.,University of Piemonte Orientale | And 2 more authors.
Critical Care | Year: 2011

We review the current literature on the molecular mechanisms involved in the pathogenesis of acute kidney injury induced by plasma mediators released by mechanical ventilation. A comprehensive literature search in the PubMed database was performed and articles were identified that showed increased plasma levels of mediators where the increase was solely attributable to mechanical ventilation. A subsequent search revealed articles delineating the potential effects of each mediator on the kidney or kidney cells. Limited research has focused specifically on the relationship between mechanical ventilation and acute kidney injury. Only a limited number of plasma mediators has been implicated in mechanical ventilation-associated acute kidney injury. The number of mediators released during mechanical ventilation is far greater and includes pro- and anti-inflammatory mediators, but also mediators involved in coagulation, fibrinolysis, cell adhesion, apoptosis and cell growth. The potential effects of these mediators is pleiotropic and include effects on inflammation, cell recruitment, adhesion and infiltration, apoptosis and necrosis, vasoactivity, cell proliferation, coagulation and fibrinolysis, transporter regulation, lipid metabolism and cell signaling. Most research has focused on inflammatory and chemotactic mediators. There is a great disparity of knowledge of potential effects on the kidney between different mediators. From a theoretical point of view, the systemic release of several mediators induced by mechanical ventilation may play an important role in the pathophysiology of acute kidney injury. However, evidence supporting a causal relationship is lacking for the studied mediators. © 2011 BioMed Central Ltd.

Van Rijn S.F.,Travel Clinic Havenziekenhuis | Van Rijn S.F.,ErasmusMC Sophia Childrens Hospital | Driessen G.,ErasmusMC Sophia Childrens Hospital | Overbosch D.,Travel Clinic Havenziekenhuis | And 3 more authors.
Journal of Travel Medicine | Year: 2012

Objective. Scarce data are available on the occurrence of ailments and diseases in children during travel. We studied the characteristics and frequencies of ailments in children aged 0 to 18 years and their parents during traveling. Methods. A prospective observational study on ailments reported by children and parents traveling to (sub)tropical countries was conducted. The ailments were semi-quantitatively graded as mild, moderate, or severe; ailments were expressed as ailment rates per personmonth of travel. Results. A total of 152 children and 47 parents kept track of their ailments for a total of 497 and 154 weeks, respectively. The children reported a mean ailment rate of 7.0 (5.6-8.4) ailments per personmonth of travel; 17.4% of the ailments were graded as moderate and 1.4% as severe. The parents reported a mean ailment rate of 4.4 (3.1-5.7); 10.8% of the ailments were graded as moderate and 5.5% as severe. Skin problems like insect bites, sunburn and itch, and abdominal complaints like diarrhea were frequently reported ailments in both children and parents. Children in the age category 12 to 18 years showed a significantly higher ailment rate of 11.2 (6.8-14.1) than their parents. Conclusions. Skin problems and abdominal problems like diarrhea are frequently reported ailments in children and their parents and show a high tendency to recur during travel. The majority of these ailments are mild but occasionally interfere with planned activities. Children in the age group 12 to 18 years are at a greater risk of developing ailments during a stay in a (sub)tropical country and they should be actively informed about the health risks of traveling to the tropics. © 2011 International Society of Travel Medicine.

Geurts D.H.F.,ErasmusMC Sophia Childrens Hospital | Vos W.,ErasmusMC Sophia Childrens Hospital | Moll H.A.,ErasmusMC Sophia Childrens Hospital | Oostenbrink R.,ErasmusMC Sophia Childrens Hospital
European Journal of Pediatrics | Year: 2014

Several guidelines exist on urinary tract infection (UTI) in children. The objectives of this study were to (1) implement an evidence-based diagnostic guideline on UTI and evaluate determinants of successful implementation, and (2) determine compliance to and impact of the guideline in febrile, non-toilet trained children at the emergency department (ED). We performed a prospective cross-sectional observational study, with observations before and after implementation. Children aged 1 month to 2 years, presenting at the ED with unexplained fever (temperature above 38.5°C), were included. We excluded children with a chronic underlying disease. Primary outcome measure was compliance to the standardized diagnostic strategy and determinants influencing compliance. Secondary outcome parameters included the following: number of used dipsticks, contaminated cultures, number of genuine UTI, frequency of prescribed antibiotic treatment, and hospitalization. The pre-intervention group {169 children (male 60.4 %, median age 1.0 [range 0.1-2.0])} was compared with the post-intervention group {150 children (male 54.7 %, median age 1.0 [range 0.1-1.9])}. In 42 patients (24.9 %), there was compliance to local guidelines before implementation, compared with 70 (46.7 %) after implementation (p-value<0.001). Improvement in compliance after implementation was higher in patients 3-24 months and outside the office hours (p<0.001). Conclusion: Implementation of a guideline for diagnosing UTI in febrile children at the ED has led to a significantly better compliance, especially in children aged 3-24 months. However, this study also underlines the need for a well-defined implementation strategy after launching an (inter)national guideline, taking determinants influencing implementation into account. © 2013 Springer-Verlag.

De Vos-Kerkhof E.,ErasmusMC Sophia Childrens Hospital | Geurts D.H.F.,ErasmusMC Sophia Childrens Hospital | Wiggers M.,Erasmus University Rotterdam | Moll H.A.,ErasmusMC Sophia Childrens Hospital | Oostenbrink R.,ErasmusMC Sophia Childrens Hospital
Archives of Disease in Childhood | Year: 2016

Context Follow-up strategies after emergency department (ED) discharge, alias safety netting, is often based on the gut feeling of the attending physician. Objective To systematically identify evaluated safetynetting strategies after ED discharge and to describe determinants of paediatric ED revisits. Data sources MEDLINE, Embase, CINAHL, Cochrane central, OvidSP, Web of Science, Google Scholar, PubMed. Study selection Studies of any design reporting on safety netting/follow-up after ED discharge and/or determinants of ED revisits for the total paediatric population or specifically for children with fever, dyspnoea and/or gastroenteritis. Outcomes included complicated course of disease after initial ED visit (eg, revisits, hospitalisation). Data extraction Two reviewers independently assessed studies for eligibility and study quality. As meta-analysis was not possible due to heterogeneity of studies, we performed a narrative synthesis of study results. A best-evidence synthesis was used to identify the level of evidence. Results We summarised 58 studies, 36% (21/58) were assessed as having low risk of bias. Limited evidence was observed for different strategies of safety netting, with educational interventions being mostly studied. Young children, a relevant medical history, infectious/ respiratory symptoms or seizures and progression/ persistence of symptoms were strongly associated with ED revisits. Gender, emergency crowding, physicians' characteristics and diagnostic tests and/or therapeutic interventions at the index visit were not associated with revisits. Conclusions Within the heterogeneous available evidence, we identified a set of strong determinants of revisits that identify high-risk groups in need for safety netting in paediatric emergency care being related to age and clinical symptoms. Gaps remain on intervention studies concerning specific application of a uniform safety-netting strategy and its included time frame.

Joosten K.,ErasmusMC Sophia Childrens Hospital | Van Puffelen E.,ErasmusMC Sophia Childrens Hospital | Verbruggen S.,ErasmusMC Sophia Childrens Hospital
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2016

Purpose of review This article describes the current best available evidence on optimal nutrition in the paediatric intensive care based on different levels of outcome, which can be divided in surrogate and hard clinical outcome parameters. Recent findings Undernutrition is associated with increased morbidity and mortality, whereas in specific cohorts of critically ill children, such as those with burn injury, obesity is associated with more complications, longer length of stay, and decreased likelihood of survival. There is a relation with adequacy of delivery of enteral nutrition and the amount of protein on length of hospital stay, neurological status, and mortality. Studies relating organ function, other than skin healing after thermal injury, with the nutritional status are scarce. There is also a scarcity of data concerning long-term follow-up and health economics. Summary Until now, there are no randomized controlled trials which have investigated a causal relation between different feeding regimens on the nutritional status and short and long-term outcome. As a result current optimal nutritional strategies are based on small trials with surrogate outcome parameters. Prospective randomized studies are needed with nutritional and/or metabolic interventions to come to an optimal feeding strategy for critically ill children. © 2016 Wolters Kluwer Health, Inc.

Hazebroek F.W.J.,ErasmusMC Sophia Childrens Hospital | Tibboel D.,ErasmusMC Sophia Childrens Hospital | Wijnen R.M.H.,ErasmusMC Sophia Childrens Hospital
Seminars in Pediatric Surgery | Year: 2014

This article places focus on three main subjects that are all related to the ethical aspects of care of newborns undergoing major surgical interventions. The first concerns the communication between the surgeon, as a representative of the treatment team, and the parents. The second is the way to handle new developments in neonatal surgery. The third issue covers several aspects of the ethical decision-making process with regard to forgoing life support in surgical neonates. These issues will be discussed on the basis of two clinical case reports. © 2014 Elsevier Inc.

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