The hospital can be a stressful environment for a child. To address the increase in demands for p... more The hospital can be a stressful environment for a child. To address the increase in demands for pediatric procedural sedation, the PROSA team initiative was started in the Leuven University Hospitals in 2014. In this study, we assessed the efficacy and safety of this project since its initiation. Demographic (age, sex) and clinical (procedure, sedation method) data were prospectively registered by the dedicated PROSA team. Anonymized data (11/2014–6/2021) were extracted to a database for analysis. Data on 5090 procedures were available. The median age was 4.8 years. The sedation was successful in 98% of patients, be it classified as ‘technically difficult’ in 3.3%. Of the 2% of failed procedures, 69% were due to inadequate sedation and 31% to logistic reasons unrelated to sedation (such as puncture problem, suboptimal bowel preparation). The overall adverse event incidence was 2% and occurred predominantly during gastro-coloscopy or bronchoscopy. Pethidine/midazolam was used in 81 c...
Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar si... more Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar simplification after prolonged hyperoxia in term rodent models of bronchopulmonary dysplasia. However, the pulmonary outcomes of postnatal TZDs have not been investigated in preterm animal models. Here, we first investigated the PPARγ selectivity, epithelial permeability, and lung tissue binding of three types of TZDs in vitro (rosiglitazone (RGZ), pioglitazone, and DRF-2546), followed by an in vivo study in preterm rabbits exposed to hyperoxia (95% oxygen) to investigate the pharmacokinetics and the pulmonary outcomes of daily RGZ administration. In addition, blood lipids and a comparative lung proteomics analysis were also performed on Day 7. All TZDs showed high epithelial permeability through Caco-2 monolayers and high plasma and lung tissue binding; however, RGZ showed the highest affinity for PPARγ. The pharmacokinetic profiling of RGZ (1 mg/kg) revealed an equivalent biodistribution...
As part of a field study (NCT04473768) in children presenting with severe febrile illness to Kisa... more As part of a field study (NCT04473768) in children presenting with severe febrile illness to Kisantu hospital (DR Congo), we retrospectively compiled user experiences (not performance) with handheld diagnostic devices assisting triage: tympanic thermometer, pulse oximeter (measuring heart rate, respiratory rate and oxygen saturation), hemoglobinometer and glucometer. Guidance documents for product selection were generic and scattered. Stock rupture, market withdrawal and unaffordable prices interfered with procurement. Challenges at implementation included environmental temperature, capillary blood sampling (antisepsis, order of multiple tests, filling microcuvettes and glucose strips), calibration (environmental temperature, cold chain) and liability-oriented communication with a manufacturer. Instructions for use were readable and contained symbol keys; two devices had printed French-language instructions. Shortcomings were poor integration of figures with text and distinct proced...
American Journal of Physiology-Lung Cellular and Molecular Physiology, 2021
Accurate fluid pressure in the fetal lung is critical for its development, especially at the begi... more Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that stretch-induced Yap/Taz activation promotes alveolar differentiation toward AT1 phenotype via ROCK activity. Our findings show that balanced ROCK-Yap/Taz signaling is essential to regulate AT1 differentiation in response to mechanical stretching of the fetal lun...
Ventilation and respiratory care have substantially changed over the last decades in extremely pr... more Ventilation and respiratory care have substantially changed over the last decades in extremely premature neonates but the impact on respiratory health remains largely unclear. To determine changes in respiratory care and disease frequency in extremely premature infants, a retrospective single-centre cohort study of extremely preterm infants was performed. All infants born alive between 24 + 0 and 27 + 6 weeks of gestation in 2000–2001 (Epoch 1), 2009–2010 (Epoch 2), and 2018–2019 (Epoch 3) were included. The primary outcome of this study was the incidence of bronchopulmonary dysplasia (BPD, diagnosed according to three different criteria) or death. Secondary outcomes included the usage of different ventilation modes, changes in pharmacotherapy, and the incidence of significant extra-pulmonary morbidities. A total of 184 neonates were included of whom 151 survived until 36 weeks of corrected GA (cGA). Oxygen or positive pressure dependence increased over time (26.1%, 41.7%, and 56.1% respectively), with higher adjusted odds in Epoch 3 for the composite outcome “BPD or death” (adjusted odds ratio: 2.55 [95%CI 1.19–5.61]). Severity-based definitions showed increasing trends in survivors only. Time spent on invasive mechanical ventilation was similar throughout the years, but the use of non-invasive ventilation significantly increased in Epoch 3 (32.0 [95%CI 25.0–37.0] vs 27.0 [95%CI 26.0–32.0] vs 53.0 [95%CI 46.0–58.0] days). Moreover, mortality-adjusted rates of severe IVH, NEC, or intestinal perforation and multiple sepsis tended to decrease. Conclusion: In spite of significant clinical advancements and adherence to novel treatment guidelines in our neonatal intensive care unit, the incidence of BPD increased over time. What is Known: • Rates of BPD are stable or increase in population-based studies. • Extremely preterm infants are particularly susceptible to developing BPD. What is New: • Despite increased use of evidence-based corticosteroid administration and early initiation of caffeine, the incidence of BPD has not decreased over the past decade. • Increased usage of non-invasive ventilation is associated with an increase of BPD incidence. What is Known: • Rates of BPD are stable or increase in population-based studies. • Extremely preterm infants are particularly susceptible to developing BPD. What is New: • Despite increased use of evidence-based corticosteroid administration and early initiation of caffeine, the incidence of BPD has not decreased over the past decade. • Increased usage of non-invasive ventilation is associated with an increase of BPD incidence.
To improve the early recognition of danger signs in children with severe febrile illness in low r... more To improve the early recognition of danger signs in children with severe febrile illness in low resource settings, WHO promotes automated respiratory rate (RR) counting, but its performance is unknown in this population. Therefore, we prospectively evaluated the field performance of automated point-of-care plethysmography-based RR counting in hospitalized children with severe febrile illness (<5 years) in DR Congo. A trained research nurse simultaneously counted the RR manually (comparative method) and automatically with the Masimo Rad G pulse oximeter. Valid paired RR measurements were obtained in 202 (83.1%) children, among whom 43.1% (87/202) had fast breathing according to WHO criteria based on manual counting. Automated counting frequently underestimated the RR (median difference of −1 breath/minute; p2.5–p97.5 limits of agreement: −34–6), particularly at higher RR. This resulted in a failure to detect fast breathing in 24.1% (21/87) of fast breathing children (positive perc...
Clinical Journal of the American Society of Nephrology, 2021
Background and objectivesAKI is a common complication after pediatric cardiac surgery and has bee... more Background and objectivesAKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery.Design, setting, participants, & measurementsPubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed.ResultsTwenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis sugge...
Reproducible and unbiased methods to quantify alveolar structure are important for research on ma... more Reproducible and unbiased methods to quantify alveolar structure are important for research on many lung diseases. However, manually estimating alveolar structure through stereology is time consuming and inter-observer variability is high. The objective of this work was to develop and validate a fast, reproducible and accurate (semi-)automatic alternative. A FIJI-macro was designed that automatically segments lung images to binary masks, and counts the number of test points falling on tissue and the number of intersections of the airtissue interface with a set of test lines. Manual selection remains necessary for the recognition of non-parenchymal tissue and alveolar exudates. Volume density of alveolar septa (V V sep) and mean linear intercept of the airspaces (Lm) as measured by the macro were compared to theoretical values for 11 artificial test images and to manually counted values for 17 lungs slides using linear regression and Bland-Altman plots. Inter-observer agreement between 3 observers, measuring 8 lungs both manually and automatically, was assessed using intraclass correlation coefficients (ICC). V V sep and Lm measured by the macro closely approached theoretical values for artificial test images (R 2 of 0.9750 and 0.9573 and bias of 0.34% and 8.7%). The macro data in lungs were slightly higher for V V sep and slightly lower for Lm in comparison to manually counted values (R 2 of 0.8262 and 0.8288 and bias of-6.0% and 12.1%). Visually, semi-automatic segmentation was accurate. Most importantly, manually counted V V sep and Lm had only moderate to good inter-observer agreement (ICC 0.859 and 0.643), but agreements were excellent for semi-automatically counted values (ICC 0.956 and 0.900). This semi-automatic method provides accurate and highly reproducible alveolar morphometry results. Future efforts should focus on refining methods for automatic detection of non-parenchymal tissue or exudates, and for assessment of lung structure on 3D reconstructions of lungs scanned with microCT.
Children and adolescents with severe burns require medical and nursing interventions, associated ... more Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic review resulted in eight studies and 142 patients. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (Standardized Mean Difference = 0.94; 95% Confidence Interval = 0.62, 1.27; Z = 5.70; p < 0.00001) for adjuvant full immersive VR compared to standard care (SC). In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with ...
Digital images might contribute to stigma associated with mental disorders. The aim of this study... more Digital images might contribute to stigma associated with mental disorders. The aim of this study was to investigate whether these images accurately represent pediatric mental disorders, as well as to explore specific image-related factors that influence perception. Methods: Four hundred pictures were retrieved from three stock photograph websites ('Shutterstock', 'iStock' and 'Adobe') and 'Google Images' for mental disorders (ADHD, ASD, and depression) and somatic diseases (asthma, diabetes, and influenza) in childhood. Each picture was scored for gender, age, and emotional load. Data was compared against data from epidemiological studies. Ordinal regression was used to predict emotional load from image-related factors. Results: There was a significant difference in gender representation of ADHD, ASD, depression, diabetes, and influenza. With respect to age, models were significantly younger in pictures of depression but older in pictures of influenza. Pictures of ASD, asthma and diabetes were mostly positive; however, images for ADHD, depression and influenza carried more negative connotations. For mental disorders, a more positive emotional load was associated with images of young and/or male models. iStock gave more positive images. Conclusions: Digital images available in stock databases do not accurately represent pediatric mental and somatic disease. For mental disorders, image-related factors (including age, gender and emotional load) may influence societal perception.
Supplemental Digital Content is available in the text Objective: To evaluate the effect of combin... more Supplemental Digital Content is available in the text Objective: To evaluate the effect of combining antenatal sildenafil with fetal tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH). Background: Although antenatal sildenafil administration rescues vascular abnormalities in lungs of fetal rabbits with CDH, it only partially improves airway morphometry. We hypothesized that we could additionally stimulate lung growth by combining this medical treatment with fetal TO. Methods: CDH was created on gestational day (GD)23 (n=54). Does were randomized to receive either sildenafil 10 mg/kg/d or placebo by subcutaneous injection from GD24 to GD30. On GD28, fetuses were randomly assigned to TO or sham neck dissection. At term (GD30) fetuses were delivered, ventilated, and finally harvested for histological and molecular analyses. Unoperated littermates served as controls. Results: The lung-to-body-weight ratio was significantly reduced in sham-CDH fetuses either (1.2 ± 0.3% vs 2.3 ± 0.3% in controls, P=0.0003). Sildenafil had no effect on this parameter, while CDH fetuses undergoing TO had a lung-to-body-weight ratio comparable to that of controls (2.5 ± 0.8%, P<0.0001). Sildenafil alone induced an improvement in the mean terminal bronchiolar density (2.5 ± 0.8 br/mm2 vs 3.5 ± 0.9 br/mm2, P=0.043) and lung mechanics (static elastance 61 ± 36 cmH2O /mL vs 113 ± 40 cmH2O/mL, P=0.008), but both effects were more pronounced in fetuses undergoing additional TO (2.1 ± 0.8 br/mm2, P=0.001 and 31 ± 9 cmH2O/mL, P<0.0001 respectively). Both CDH-sham and CDH-TO fetuses treated with placebo had an increased medial wall thickness of peripheral pulmonary vessels (41.9 ± 2.9% and 41.8 ± 3.2%, vs 24.0 ± 2.9% in controls, P<0.0001). CDH fetuses treated with sildenafil, either with or without TO, had a medial thickness in the normal range (29.4% ± 2.6%). Finally, TO reduced gene expression of vascular endothelial growth factor and surfactant protein A and B, but this effect was counteracted by sildenafil. Conclusion: In the rabbit model for CDH, the combination of maternal sildenafil and TO has a complementary effect on vascular and parenchymal lung development.
Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity througho... more Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. Methods Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. Results Preterm pups assessed at birth depicted a more rudimentary lung stru...
Background: The use of the internet as a source of information has grown exponentially in the las... more Background: The use of the internet as a source of information has grown exponentially in the last decade. YouTube is currently the second most visited website and a major Web-based educational resource for medical students. Objective: The aim of this study was to evaluate the quality, accuracy, and attractiveness of the information acquired from YouTube videos about 2 central concepts in immunology. Methods: YouTube videos posted before August 27, 2018 were searched using selected keywords related to either antigen presentation or immunoglobulin gene rearrangement. Video characteristics were recorded, and the Video Power Index (VPI) was calculated. Videos were assessed using 5 validated scoring systems: understandability and attractiveness, reliability, content and comprehensiveness, global quality score (GQS), and a subjective score. Videos were categorized by educational usefulness and by source. Results: A total of 82 videos about antigen presentation and 70 about immunoglobulin gene rearrangement were analyzed. Videos had a mean understandability and attractiveness score of 6.57/8 and 5.84/8, content and comprehensiveness score of 9.84/20 and 5.84/20, reliability score of 1.65/4 and 1.53/4, GQS of 3.38/5 and 2.76/5, and subjective score of 2.00/3 and 2.00/3, respectively. The organized channels group tended to have the highest VPI and GQS. Conclusions: YouTube can provide medical students with some useful information about immunology, although content wise it cannot substitute textbooks and academic courses. Students and teachers should be aware of the educational quality of available videos if they intend to use them in the context of blended learning.
American journal of obstetrics and gynecology, Jan 4, 2018
Sildenafil is already administered during gestation in patients with pulmonary hypertension and i... more Sildenafil is already administered during gestation in patients with pulmonary hypertension and is under evaluation as a treatment for several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction. Animal studies have shown a potential therapeutic effect of the drug in fetuses with congenital diaphragmatic hernia, rescuing peripheral pulmonary vasculature and airway phenotype. When considering this drug for evaluation in a clinical trial, data on effective human placental drug passage are required. We quantified transplacental passage of sildenafil in the ex vivo dually perfused cotyledon model. Six placentas were collected after term delivery from healthy volunteers, cannulated and dually perfused. Sildenafil citrate was added to the maternal circulation at two different concentrations: 500 ng/mL, representing the maximum tolerated concentration (N=3) and 50 ng/mL, representing the therapeutic concentration (N=3). Samples were collected from both the fe...
Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. ... more Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. The main problem is that herniation of viscera during fetal development impairs lung development, leading to a 30 % mortality and significant morbidity. In isolated cases the outcome can be accurately predicted prenatally by medical imaging. Cases with a poor prognosis can be treated before birth; clinically this is by fetoscopic endoluminal tracheal occlusion. Obstruction of the airways triggers lung growth. This procedure and is currently being evaluated in a global clinical trial for left sided cases; right sided cases with poor prognosis are offered the procedure clinically. The search for more potent and less invasive therapies continues. Prenatal transplacental sildenafil administration will in due course be tried clinically, with the aim to reduce the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery. Other medical approaches are in...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants... more Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants and remains - despite improvements in neonatal intensive care - a major cause of neonatal mortality and morbidity. Cell-therapeutic strategies employing mesenchymal stem cells (MSC) have been shown to modulate lung development in BPD models. Herein, we evaluate the potential of human amniotic fluid (hAF)-SC and hAF-SC with upregulated expression of vascular endothelial growth factor (VEGF) as cell-therapeutic agents for BPD. Preterm rabbit pups were raised in normoxia (21% O2) or hyperoxia (≥95% O2). Hyperoxia-exposed pups randomly received an intraperitoneal injection of fibroblasts, naïve hAF-SC, or hAF-SC-VEGF on postnatal day (PN) 0. On PN7, surviving pups were tested for pulmonary (forced oscillation technique) and vascular (pulmonary artery Doppler ultrasound) function, and lungs were processed for morphometric measurements of parenchymal and vascular structure and inflammation. I...
Seminars in fetal & neonatal medicine, Dec 1, 2017
Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determin... more Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determines mortality and morbidity. In isolated cases the outcome may be predicted prenatally by medical imaging. Cases with a poor prognosis could be treated before birth. However, prenatal modulation of lung development remains experimental. Fetoscopic endoluminal tracheal occlusion triggers lung growth and is currently being evaluated in a global clinical trial. Prenatal transplacental sildenafil administration may in due course be a therapeutic approach, reducing the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery.
The hospital can be a stressful environment for a child. To address the increase in demands for p... more The hospital can be a stressful environment for a child. To address the increase in demands for pediatric procedural sedation, the PROSA team initiative was started in the Leuven University Hospitals in 2014. In this study, we assessed the efficacy and safety of this project since its initiation. Demographic (age, sex) and clinical (procedure, sedation method) data were prospectively registered by the dedicated PROSA team. Anonymized data (11/2014–6/2021) were extracted to a database for analysis. Data on 5090 procedures were available. The median age was 4.8 years. The sedation was successful in 98% of patients, be it classified as ‘technically difficult’ in 3.3%. Of the 2% of failed procedures, 69% were due to inadequate sedation and 31% to logistic reasons unrelated to sedation (such as puncture problem, suboptimal bowel preparation). The overall adverse event incidence was 2% and occurred predominantly during gastro-coloscopy or bronchoscopy. Pethidine/midazolam was used in 81 c...
Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar si... more Thiazolidinediones (TZDs) are potent PPARγ agonists that have been shown to attenuate alveolar simplification after prolonged hyperoxia in term rodent models of bronchopulmonary dysplasia. However, the pulmonary outcomes of postnatal TZDs have not been investigated in preterm animal models. Here, we first investigated the PPARγ selectivity, epithelial permeability, and lung tissue binding of three types of TZDs in vitro (rosiglitazone (RGZ), pioglitazone, and DRF-2546), followed by an in vivo study in preterm rabbits exposed to hyperoxia (95% oxygen) to investigate the pharmacokinetics and the pulmonary outcomes of daily RGZ administration. In addition, blood lipids and a comparative lung proteomics analysis were also performed on Day 7. All TZDs showed high epithelial permeability through Caco-2 monolayers and high plasma and lung tissue binding; however, RGZ showed the highest affinity for PPARγ. The pharmacokinetic profiling of RGZ (1 mg/kg) revealed an equivalent biodistribution...
As part of a field study (NCT04473768) in children presenting with severe febrile illness to Kisa... more As part of a field study (NCT04473768) in children presenting with severe febrile illness to Kisantu hospital (DR Congo), we retrospectively compiled user experiences (not performance) with handheld diagnostic devices assisting triage: tympanic thermometer, pulse oximeter (measuring heart rate, respiratory rate and oxygen saturation), hemoglobinometer and glucometer. Guidance documents for product selection were generic and scattered. Stock rupture, market withdrawal and unaffordable prices interfered with procurement. Challenges at implementation included environmental temperature, capillary blood sampling (antisepsis, order of multiple tests, filling microcuvettes and glucose strips), calibration (environmental temperature, cold chain) and liability-oriented communication with a manufacturer. Instructions for use were readable and contained symbol keys; two devices had printed French-language instructions. Shortcomings were poor integration of figures with text and distinct proced...
American Journal of Physiology-Lung Cellular and Molecular Physiology, 2021
Accurate fluid pressure in the fetal lung is critical for its development, especially at the begi... more Accurate fluid pressure in the fetal lung is critical for its development, especially at the beginning of the saccular stage when alveolar epithelial type 1 (AT1) and type 2 (AT2) cells differentiate from the epithelial progenitors. Despite our growing understanding of the role of physical forces in lung development, the molecular mechanisms that regulate the transduction of mechanical stretch to alveolar differentiation remain elusive. To simulate lung distension, we optimized both an ex vivo model with precision cut lung slices and an in vivo model of fetal tracheal occlusion. Increased mechanical tension showed to improve alveolar maturation and differentiation toward AT1. By manipulating ROCK pathway, we demonstrate that stretch-induced Yap/Taz activation promotes alveolar differentiation toward AT1 phenotype via ROCK activity. Our findings show that balanced ROCK-Yap/Taz signaling is essential to regulate AT1 differentiation in response to mechanical stretching of the fetal lun...
Ventilation and respiratory care have substantially changed over the last decades in extremely pr... more Ventilation and respiratory care have substantially changed over the last decades in extremely premature neonates but the impact on respiratory health remains largely unclear. To determine changes in respiratory care and disease frequency in extremely premature infants, a retrospective single-centre cohort study of extremely preterm infants was performed. All infants born alive between 24 + 0 and 27 + 6 weeks of gestation in 2000–2001 (Epoch 1), 2009–2010 (Epoch 2), and 2018–2019 (Epoch 3) were included. The primary outcome of this study was the incidence of bronchopulmonary dysplasia (BPD, diagnosed according to three different criteria) or death. Secondary outcomes included the usage of different ventilation modes, changes in pharmacotherapy, and the incidence of significant extra-pulmonary morbidities. A total of 184 neonates were included of whom 151 survived until 36 weeks of corrected GA (cGA). Oxygen or positive pressure dependence increased over time (26.1%, 41.7%, and 56.1% respectively), with higher adjusted odds in Epoch 3 for the composite outcome “BPD or death” (adjusted odds ratio: 2.55 [95%CI 1.19–5.61]). Severity-based definitions showed increasing trends in survivors only. Time spent on invasive mechanical ventilation was similar throughout the years, but the use of non-invasive ventilation significantly increased in Epoch 3 (32.0 [95%CI 25.0–37.0] vs 27.0 [95%CI 26.0–32.0] vs 53.0 [95%CI 46.0–58.0] days). Moreover, mortality-adjusted rates of severe IVH, NEC, or intestinal perforation and multiple sepsis tended to decrease. Conclusion: In spite of significant clinical advancements and adherence to novel treatment guidelines in our neonatal intensive care unit, the incidence of BPD increased over time. What is Known: • Rates of BPD are stable or increase in population-based studies. • Extremely preterm infants are particularly susceptible to developing BPD. What is New: • Despite increased use of evidence-based corticosteroid administration and early initiation of caffeine, the incidence of BPD has not decreased over the past decade. • Increased usage of non-invasive ventilation is associated with an increase of BPD incidence. What is Known: • Rates of BPD are stable or increase in population-based studies. • Extremely preterm infants are particularly susceptible to developing BPD. What is New: • Despite increased use of evidence-based corticosteroid administration and early initiation of caffeine, the incidence of BPD has not decreased over the past decade. • Increased usage of non-invasive ventilation is associated with an increase of BPD incidence.
To improve the early recognition of danger signs in children with severe febrile illness in low r... more To improve the early recognition of danger signs in children with severe febrile illness in low resource settings, WHO promotes automated respiratory rate (RR) counting, but its performance is unknown in this population. Therefore, we prospectively evaluated the field performance of automated point-of-care plethysmography-based RR counting in hospitalized children with severe febrile illness (<5 years) in DR Congo. A trained research nurse simultaneously counted the RR manually (comparative method) and automatically with the Masimo Rad G pulse oximeter. Valid paired RR measurements were obtained in 202 (83.1%) children, among whom 43.1% (87/202) had fast breathing according to WHO criteria based on manual counting. Automated counting frequently underestimated the RR (median difference of −1 breath/minute; p2.5–p97.5 limits of agreement: −34–6), particularly at higher RR. This resulted in a failure to detect fast breathing in 24.1% (21/87) of fast breathing children (positive perc...
Clinical Journal of the American Society of Nephrology, 2021
Background and objectivesAKI is a common complication after pediatric cardiac surgery and has bee... more Background and objectivesAKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery.Design, setting, participants, & measurementsPubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed.ResultsTwenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis sugge...
Reproducible and unbiased methods to quantify alveolar structure are important for research on ma... more Reproducible and unbiased methods to quantify alveolar structure are important for research on many lung diseases. However, manually estimating alveolar structure through stereology is time consuming and inter-observer variability is high. The objective of this work was to develop and validate a fast, reproducible and accurate (semi-)automatic alternative. A FIJI-macro was designed that automatically segments lung images to binary masks, and counts the number of test points falling on tissue and the number of intersections of the airtissue interface with a set of test lines. Manual selection remains necessary for the recognition of non-parenchymal tissue and alveolar exudates. Volume density of alveolar septa (V V sep) and mean linear intercept of the airspaces (Lm) as measured by the macro were compared to theoretical values for 11 artificial test images and to manually counted values for 17 lungs slides using linear regression and Bland-Altman plots. Inter-observer agreement between 3 observers, measuring 8 lungs both manually and automatically, was assessed using intraclass correlation coefficients (ICC). V V sep and Lm measured by the macro closely approached theoretical values for artificial test images (R 2 of 0.9750 and 0.9573 and bias of 0.34% and 8.7%). The macro data in lungs were slightly higher for V V sep and slightly lower for Lm in comparison to manually counted values (R 2 of 0.8262 and 0.8288 and bias of-6.0% and 12.1%). Visually, semi-automatic segmentation was accurate. Most importantly, manually counted V V sep and Lm had only moderate to good inter-observer agreement (ICC 0.859 and 0.643), but agreements were excellent for semi-automatically counted values (ICC 0.956 and 0.900). This semi-automatic method provides accurate and highly reproducible alveolar morphometry results. Future efforts should focus on refining methods for automatic detection of non-parenchymal tissue or exudates, and for assessment of lung structure on 3D reconstructions of lungs scanned with microCT.
Children and adolescents with severe burns require medical and nursing interventions, associated ... more Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic review resulted in eight studies and 142 patients. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (Standardized Mean Difference = 0.94; 95% Confidence Interval = 0.62, 1.27; Z = 5.70; p < 0.00001) for adjuvant full immersive VR compared to standard care (SC). In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with ...
Digital images might contribute to stigma associated with mental disorders. The aim of this study... more Digital images might contribute to stigma associated with mental disorders. The aim of this study was to investigate whether these images accurately represent pediatric mental disorders, as well as to explore specific image-related factors that influence perception. Methods: Four hundred pictures were retrieved from three stock photograph websites ('Shutterstock', 'iStock' and 'Adobe') and 'Google Images' for mental disorders (ADHD, ASD, and depression) and somatic diseases (asthma, diabetes, and influenza) in childhood. Each picture was scored for gender, age, and emotional load. Data was compared against data from epidemiological studies. Ordinal regression was used to predict emotional load from image-related factors. Results: There was a significant difference in gender representation of ADHD, ASD, depression, diabetes, and influenza. With respect to age, models were significantly younger in pictures of depression but older in pictures of influenza. Pictures of ASD, asthma and diabetes were mostly positive; however, images for ADHD, depression and influenza carried more negative connotations. For mental disorders, a more positive emotional load was associated with images of young and/or male models. iStock gave more positive images. Conclusions: Digital images available in stock databases do not accurately represent pediatric mental and somatic disease. For mental disorders, image-related factors (including age, gender and emotional load) may influence societal perception.
Supplemental Digital Content is available in the text Objective: To evaluate the effect of combin... more Supplemental Digital Content is available in the text Objective: To evaluate the effect of combining antenatal sildenafil with fetal tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH). Background: Although antenatal sildenafil administration rescues vascular abnormalities in lungs of fetal rabbits with CDH, it only partially improves airway morphometry. We hypothesized that we could additionally stimulate lung growth by combining this medical treatment with fetal TO. Methods: CDH was created on gestational day (GD)23 (n=54). Does were randomized to receive either sildenafil 10 mg/kg/d or placebo by subcutaneous injection from GD24 to GD30. On GD28, fetuses were randomly assigned to TO or sham neck dissection. At term (GD30) fetuses were delivered, ventilated, and finally harvested for histological and molecular analyses. Unoperated littermates served as controls. Results: The lung-to-body-weight ratio was significantly reduced in sham-CDH fetuses either (1.2 ± 0.3% vs 2.3 ± 0.3% in controls, P=0.0003). Sildenafil had no effect on this parameter, while CDH fetuses undergoing TO had a lung-to-body-weight ratio comparable to that of controls (2.5 ± 0.8%, P<0.0001). Sildenafil alone induced an improvement in the mean terminal bronchiolar density (2.5 ± 0.8 br/mm2 vs 3.5 ± 0.9 br/mm2, P=0.043) and lung mechanics (static elastance 61 ± 36 cmH2O /mL vs 113 ± 40 cmH2O/mL, P=0.008), but both effects were more pronounced in fetuses undergoing additional TO (2.1 ± 0.8 br/mm2, P=0.001 and 31 ± 9 cmH2O/mL, P<0.0001 respectively). Both CDH-sham and CDH-TO fetuses treated with placebo had an increased medial wall thickness of peripheral pulmonary vessels (41.9 ± 2.9% and 41.8 ± 3.2%, vs 24.0 ± 2.9% in controls, P<0.0001). CDH fetuses treated with sildenafil, either with or without TO, had a medial thickness in the normal range (29.4% ± 2.6%). Finally, TO reduced gene expression of vascular endothelial growth factor and surfactant protein A and B, but this effect was counteracted by sildenafil. Conclusion: In the rabbit model for CDH, the combination of maternal sildenafil and TO has a complementary effect on vascular and parenchymal lung development.
Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity througho... more Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. Methods Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. Results Preterm pups assessed at birth depicted a more rudimentary lung stru...
Background: The use of the internet as a source of information has grown exponentially in the las... more Background: The use of the internet as a source of information has grown exponentially in the last decade. YouTube is currently the second most visited website and a major Web-based educational resource for medical students. Objective: The aim of this study was to evaluate the quality, accuracy, and attractiveness of the information acquired from YouTube videos about 2 central concepts in immunology. Methods: YouTube videos posted before August 27, 2018 were searched using selected keywords related to either antigen presentation or immunoglobulin gene rearrangement. Video characteristics were recorded, and the Video Power Index (VPI) was calculated. Videos were assessed using 5 validated scoring systems: understandability and attractiveness, reliability, content and comprehensiveness, global quality score (GQS), and a subjective score. Videos were categorized by educational usefulness and by source. Results: A total of 82 videos about antigen presentation and 70 about immunoglobulin gene rearrangement were analyzed. Videos had a mean understandability and attractiveness score of 6.57/8 and 5.84/8, content and comprehensiveness score of 9.84/20 and 5.84/20, reliability score of 1.65/4 and 1.53/4, GQS of 3.38/5 and 2.76/5, and subjective score of 2.00/3 and 2.00/3, respectively. The organized channels group tended to have the highest VPI and GQS. Conclusions: YouTube can provide medical students with some useful information about immunology, although content wise it cannot substitute textbooks and academic courses. Students and teachers should be aware of the educational quality of available videos if they intend to use them in the context of blended learning.
American journal of obstetrics and gynecology, Jan 4, 2018
Sildenafil is already administered during gestation in patients with pulmonary hypertension and i... more Sildenafil is already administered during gestation in patients with pulmonary hypertension and is under evaluation as a treatment for several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction. Animal studies have shown a potential therapeutic effect of the drug in fetuses with congenital diaphragmatic hernia, rescuing peripheral pulmonary vasculature and airway phenotype. When considering this drug for evaluation in a clinical trial, data on effective human placental drug passage are required. We quantified transplacental passage of sildenafil in the ex vivo dually perfused cotyledon model. Six placentas were collected after term delivery from healthy volunteers, cannulated and dually perfused. Sildenafil citrate was added to the maternal circulation at two different concentrations: 500 ng/mL, representing the maximum tolerated concentration (N=3) and 50 ng/mL, representing the therapeutic concentration (N=3). Samples were collected from both the fe...
Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. ... more Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. The main problem is that herniation of viscera during fetal development impairs lung development, leading to a 30 % mortality and significant morbidity. In isolated cases the outcome can be accurately predicted prenatally by medical imaging. Cases with a poor prognosis can be treated before birth; clinically this is by fetoscopic endoluminal tracheal occlusion. Obstruction of the airways triggers lung growth. This procedure and is currently being evaluated in a global clinical trial for left sided cases; right sided cases with poor prognosis are offered the procedure clinically. The search for more potent and less invasive therapies continues. Prenatal transplacental sildenafil administration will in due course be tried clinically, with the aim to reduce the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery. Other medical approaches are in...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants... more Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants and remains - despite improvements in neonatal intensive care - a major cause of neonatal mortality and morbidity. Cell-therapeutic strategies employing mesenchymal stem cells (MSC) have been shown to modulate lung development in BPD models. Herein, we evaluate the potential of human amniotic fluid (hAF)-SC and hAF-SC with upregulated expression of vascular endothelial growth factor (VEGF) as cell-therapeutic agents for BPD. Preterm rabbit pups were raised in normoxia (21% O2) or hyperoxia (≥95% O2). Hyperoxia-exposed pups randomly received an intraperitoneal injection of fibroblasts, naïve hAF-SC, or hAF-SC-VEGF on postnatal day (PN) 0. On PN7, surviving pups were tested for pulmonary (forced oscillation technique) and vascular (pulmonary artery Doppler ultrasound) function, and lungs were processed for morphometric measurements of parenchymal and vascular structure and inflammation. I...
Seminars in fetal & neonatal medicine, Dec 1, 2017
Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determin... more Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determines mortality and morbidity. In isolated cases the outcome may be predicted prenatally by medical imaging. Cases with a poor prognosis could be treated before birth. However, prenatal modulation of lung development remains experimental. Fetoscopic endoluminal tracheal occlusion triggers lung growth and is currently being evaluated in a global clinical trial. Prenatal transplacental sildenafil administration may in due course be a therapeutic approach, reducing the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery.
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Papers by jaan Toelen