12 research outputs found

    One Size Does Not Fit All: prognosis and therapy in congenital diaphragmatic hernia

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    Predicting prognosis in newborns with congenital diaphragmatic hernia in early life. Development of therapy for congenital diaphragmatic hernia in the acute phase

    Perinatal stabilisation of infants born with congenital diaphragmatic hernia: A review of current concepts

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    Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, th

    Children with severe acute asthma admitted to Dutch PICUs: A changing landscape

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    The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. Objectives: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. Methods: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. Results: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P<0.001) and fewer children needed invasive ventilation (P<0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P=0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P=0.004), with a significant increase in both age groups (2-4 years [P=0.026] and 5-17 years [P=0.036]). Conclusions: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals

    Pharmacokinetic modeling of intravenous sildenafil in newborns with congenital diaphragmatic hernia

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    Purpose: We developed a pharmacokinetic model of intravenous sildenafil in newborns with congenital diaphragmatic hernia (CDH) to achieve a target plasma concentration of over 50 μg/l. Methods: Twenty-three CDH newborns with pulmonary hypertension (64 blood samples) received intravenous sildenafil. Patients received a loading dose of 0.35 mg/kg (IQR 0.16 mg/kg) for 3 h, followed by a continuous infusion of 1.5 mg/kg/day (IQR 0.1 mg/kg/day). For model development, non-linear mixed modeling was used. Inter-individual variability (IIV) and inter-occasion variability were tested. Demographic and laboratory parameters were evaluated as covariates. Normalized prediction distribution errors (NPDE) and visual predictive check (VPC) were used for model validation. Results: A two-compartment disposition model of sildenafil and a one-compartment disposition model of desmethyl sildenafil (DMS) was observed with IIV in sildenafil and DMS clearance and volume of distribution of sildenafil. NPDE and VPC revealed adequate predictability. Only postnatal age increased sildenafil clearance. This was partly compensated by a higher DMS concentration, which also has a therapeutic effect. In this small group of patients, sildenafil was tolerated well. Conclusions: This model for sildenafil in CDH patients shows that concentration-targeted sildenafil dosing of 0.4 mg/kg in 3 h, followed by 1.6 mg/kg/day continuous infusion achieves appropriate sildenafil plasma levels

    Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia

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    OBJECTIVE: To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding lg-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in extremely premature infants.METHODS AND RESULTS: Proteome screening in first-week-of-life plasma samples of n- 52 preterm infants <32 weeks gestational age (GA) on two proteomic platforms (SomaLogic (R), Olink-Proteomics (R)) confirmed three biomarkers with significant predictive power: BCAM, SIGLEC-14, and ANGPTL-3. We demonstrate high sensitivity (0.92) and specificity (0.86) under consideration of GA, show the proteins' critical contribution to the predictive power of known clinical risk factors, e.g., birth weight and GA, and predicted the duration of mechanical ventilation, oxygen supplementation, as well as neonatal intensive care stay. We confirmed significant predictive power for BPD cases when switching to a clinically applicable method (enzyme-linked immunosorbent assay) in an independent sample set (n = 25, p < 0.001) and demonstrated disease specificity in different cohorts of neonatal and adult lung disease.CONCLUSION: While successfully addressing typical challenges of clinical biomarker studies, we demonstrated the potential of BCAM, SIGLEC-14, and ANGPTL-3 to inform future clinical decision making in the preterm infant at risk for BPD.Analytical BioScience

    Neonatale hemochromatose als oorzaak van leverfalen.

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    Major sacrococcygeal teratoma in an extreme premature infant: a multidisciplinary approach.

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    Antenatally diagnosed, large sacrococcygeal teratomas in very premature infants are associated with a very poor outcome. We present an extreme premature infant with cardiac decompensation, diagnosed at 27 weeks and 1 day of gestational age. A positive outcome could be achieved with intensive multidisciplinary planning of the delivery, postnatal stabilization and surgical resection, as demonstrated in this case report

    An Accidental Repetitive 10-Fold Overdose of Sildenafil in a Young Infant with Pulmonary Hypertension

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    Sildenafil is a selective phosphodiesterase type-5 inhibitor that is increasingly used to treat pulmonary hypertension (PH) in neonates. Only little is known about the relation between the dose of sildenafil, plasma concentrations, and the degree of toxicity. Here, we present a young infant with congenital diaphragmatic hernia and PH who received an unintentional 10-fold overdose of oral sildenafil for 6 consecutive days. This overdose, compared to the therapeutic dose, resulted in increased plasma concentrations of sildenafil from 42 to 521 mcg/L and desmethylsildenafil from 81 to 393 mcg/L. However, the high exposure only led to diarrhea, without any other serious adverse events. This case describes the mild symptoms upon an overdose with the role of therapeutic drug monitoring to monitor exposure in rela

    Children with severe acute asthma admitted to Dutch PICUs: A changing landscape

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    The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. OBJECTIVES: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. METHODS: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. RESULTS: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer children needed invasive ventilation (P < 0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1 mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P = 0.005). The proportion of steroid-naive patients increased from 35% to 54% (P = 0.004), with a significant increase in both age groups (2-4 years [P = 0.026] and 5-17 years [P = 0.036]). CONCLUSIONS: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naive children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals
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