Lung-borne systemic inflammation in mechanically ventilated infant rats due to high PEEP, oxygen, and hypocapnia

Background: Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response. Methods: Fourteen-day old Wistar rat pups were randomized to the following groups: (a) “control” with tidal volume ~8 mL/kg, PEEP 5 cmH2O, FiO2 0.4, RR 90 min-1, (b) “PEEP 1”, (c) “PEEP 9” (d) “FiO2 0.21”, (e) “FiO2 1.0”, (f) “hypocapnia” with RR of 180 min-1, and (g) “hypercapnia” with RR of 60 min-1. Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment. Results: Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were driven by FiO2 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH2O, P<0.05) and hypocapnia (P<0.05), and TNF-α was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected. Conclusion: Alterations of PEEP, FiO2, and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants

Macitentan attenuates cardiovascular remodelling in infant rats with chronic lung disease

Background Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling. Methods In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO2) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed. Results FiO2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p  0.05). Conclusion The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease

Interpretable Anomaly Detection in Echocardiograms with Dynamic Variational Trajectory Models

We propose a novel anomaly detection method for echocardiogram videos. The introduced method takes advantage of the periodic nature of the heart cycle to learn three variants of a variational latent trajectory model (TVAE). While the first two variants (TVAE-C and TVAE-R) model strict periodic movements of the heart, the third (TVAE-S) is more general and allows shifts in the spatial representation throughout the video. All models are trained on the healthy samples of a novel in-house dataset of infant echocardiogram videos consisting of multiple chamber views to learn a normative prior of the healthy population. During inference, maximum a posteriori (MAP) based anomaly detection is performed to detect out-of-distribution samples in our dataset. The proposed method reliably identifies severe congenital heart defects, such as Ebstein's Anomaly or Shone-complex. Moreover, it achieves superior performance over MAP-based anomaly detection with standard variational autoencoders when detecting pulmonary hypertension and right ventricular dilation. Finally, we demonstrate that the proposed method enables interpretable explanations of its output through heatmaps highlighting the regions corresponding to anomalous heart structures.Comment: accepted at IMLH workshop ICML 202

Incidence of neonatal respiratory morbidity after vaginal and caesarean delivery in the late-preterm and term period - a retrospective cohort study

BACKGROUND Respiratory distress syndrome is a leading cause of neonatal intensive care unit admissions for late preterm (34-36 weeks gestational age) and term infants (37-41 weeks). The risk for respiratory morbidity appears to increase after an elective caesarean delivery and might be reduced after antenatal corticosteroids. However, before considering antenatal corticosteroids for women at high risk of preterm birth after 34 weeks, the incidence of respiratory distress syndrome and the effect of delivery mode on this incidence requires further evaluation. Therefore, this study aimed to investigate the relationship between respiratory distress syndrome incidence and delivery mode in late preterm and term infants. METHODS In this retrospective cohort study, the clinical databases of the University Hospitals of Zurich and Basel were queried regarding all live births between 34 + 0 and 41 + 6 weeks. Neonatal intensive care unit admissions due to respiratory distress syndrome were determined and analysed in regard to the following delivery modes: spontaneous vaginal, operative vaginal, elective caesarean, secondary caesarean and emergency caesarean. RESULTS After excluding malformations (n = 889) and incomplete or inconclusive data (n = 383), 37,110 infants out of 38,382 were evaluated. Of these, 5.34% (n = 1980) were admitted to a neonatal intensive care unit for respiratory distress syndrome. Regardless of gestational age, respiratory distress syndrome in infants after spontaneous vaginal delivery was 2.92%; for operative vaginal delivery, it was 4.02%; after elective caesarean delivery it was 8.98%; following secondary caesarean delivery, it was 8.45%, and after an emergency caesarean it was 13.3%. The risk of respiratory distress syndrome was higher after an elective caesarean compared to spontaneous vaginal delivery, with an odds ratio (OR), adjusted for gestational age, of 2.31 (95% CI 1.49-3.56) at 34 weeks, OR 5.61 (95% CI 3.39-9.3) at 35 weeks, OR 1.5 (95% CI 0.95-2.38) at 36 weeks, OR 3.28 (95% CI 1.95-5.54) at 37 weeks and OR 2.51 (95% CI 1.65-3.81) at 38 weeks. At 39 weeks, there was no significant difference between the risk of respiratory distress syndrome after an elective caesarean vs. spontaneous vaginal delivery. Over the study period, gestational age at elective caesarean delivery remained stable at 39.3 ± 1.65 weeks. CONCLUSION The incidence of respiratory distress syndrome following an elective caesarean is up to threefold higher in infants born with less than 39 weeks gestational age compared to those born by spontaneous vaginal delivery. Therefore - and whenever possible - an elective caesarean delivery should be planned after 38 completed weeks to minimise the risk of respiratory morbidity in neonates

Pancreatic Insufficiency, Digestive Enzyme Supplementation, and Postnatal Growth in Preterm Babies

Background: Optimising postnatal growth facilitates better long-term neonatal neurodevelopmental outcomes. Early postnatal growth is often hindered by a variety of factors unique to the extrauterine environment and digestive immaturity both contributing to reduced enteral feed tolerance during the first few days and weeks after birth. Preterm infants display varying levels of pancreatic insufficiency that are related to gestational age and providing digestive enzyme supplementation, may be one way in which to improve postnatal growth in enterally fed preterm babies. Summary: In this review, we explore which exocrine pancreatic enzymes are deficient in preterm babies, the methods by which exocrine pancreatic function is measured, potential avenues by which digestive enzyme replacement might improve postnatal growth failure, and which babies might benefit most from this intervention. Key Messages: Pancreatic exocrine function exhibits developmental immaturity in extremely preterm infants and may contribute to postnatal growth failure. Stool elastase is a simple, non-invasive method of assessing pancreatic function in preterm infants. Available evidence does not currently support routine use of digestive enzyme supplementation in preterm infants

Pancreatic insufficiency, digestive enzyme supplementation, and postnatal growth in preterm babies

Background: Optimising postnatal growth facilitates better long-term neonatal neurodevelopmental outcomes. Early postnatal growth is often hindered by a variety of factors unique to the extrauterine environment and digestive immaturity both contributing to reduced enteral feed tolerance during the first few days and weeks after birth. Preterm infants display varying levels of pancreatic insufficiency that are related to gestational age and providing digestive enzyme supplementation, may be one way in which to improve postnatal growth in enterally fed preterm babies. Summary: In this review, we explore which exocrine pancreatic enzymes are deficient in preterm babies, the methods by which exocrine pancreatic function is measured, potential avenues by which digestive enzyme replacement might improve postnatal growth failure, and which babies might benefit most from this intervention. Key Messages: Pancreatic exocrine function exhibits developmental immaturity in extremely preterm infants and may contribute to postnatal growth failure. Stool elastase is a simple, non-invasive method of assessing pancreatic function in preterm infants. Available evidence does not currently support routine use of digestive enzyme supplementation in preterm infants

Neurofilament Light Chain as Biomarker in Encephalitis

Inflammation of the brain is called encephalitis and may result in acute and chronic brain damage. Encephalitis can be caused by various pathogens, especially neurotropic viruses, or can occur in the context of autoimmune diseases. Encephalitis is often difficult to diagnose and to monitor precisely during the course of the disease. Thanks to highly specific detection technology, components of the neuron skeleton, such as neurofilaments, can now be reliably quantified in the peripheral blood besides cerebrospinal fluid (CSF). Among them, neurofilament light chain (NfL) has demonstrated wide utility due to high preanalytical stability, robust diagnostic technology, and excellent reproducibility. We provide an overview of how NfL has advanced diagnostics in encephalitis and outline future avenues in research needs and possible clinical applicability of NfL in adults and children

Ectopic Atrial Tachycardia in a 12-Month-Old Girl Treated With Ivabradine and Beta-Blocker, a Case Report

We report on a 12-month-old girl with an ectopic atrial tachycardia successfully treated with the combination of a beta blocking agent and Ivabradine that acts on cardiac pacemaker cells by selectively inhibiting the I(f)channel. Standard therapy had failed to control the tachycardia before. No side effects attributable to Ivabradine were noticed. Due to its mechanism of action Ivabradine is a promising novel agent for the therapy of tachycardia due to increased automaticity. Reports on the use of Ivabradine in young children or infants are rare, but show promising results for congenital junctional ectopic tachycardia. This report adds the second case of ectopic atrial tachycardia in this age group and novel treatment with Ivabradine to the literature

Opinion Paper: Rationale for Supra-National Training in Neonatology

Introduction: Clinical training in neonatology takes place where neonates are cared for, at the cot-side, in neonatal units. Neonatal units vary widely in size, specialization, resources, staffing and academic level. Among them, small units make up a large proportion which have more difficulties to offer structured training courses on site, local expertise on all relevant neonatal topics, and appropriate exposition of the trainee to high-risk cases. Although evidence-based medicine is widely accepted, training of physicians, including neonatologists, often follows ineffective learning methods, or even less favorable, learning by doing. When looking at the national training requirements and standards within Europe, there are large differences between countries. Some countries have training requirements, standards and national training courses in place other countries have none of this. Therefore, it is worthwhile to create a supra-regional or even supra-national training program that complements local clinical work on an individual basis to provide structured training and evidence-based education anywhere and anytime. The European Society for Paediatric Research (ESPR) has long been committed to the education and training of medical doctors specializing in neonatology. Together with the European Board of Neonatology (EBN), which is a substructure of ESPR devoted to the design and implementation of a syllabus that comprises the theoretical and practical needs for the European Training in Neonatology, the European Training Requirements (ETR) in Neonatology has been developed. The 2021 updated syllabus, the current ETR in Neonatology, is based on the previous 2007 syllabus version and has been approved by the Union of European Medicine Specialist (EAMS) in April 2021. Interestingly, the 2021 syllabus content was updated by the EBN members, but also critically incorporated and comments suggestions of national representatives of 30 European countries following two sequential surveys and face to face meetings. Each country pertaining to the EBN has a different national training curriculum to achieve the training standards required to exert as neonatologists. The aim of the ETR in Neonatology has been to harmonize training requirements within Europe to achieving a basic and reliable standard of quality in theoretical knowledge and practical skills alongside the European countries. We present an online training concept that meets the needs of neonatal training situations and implements the latest effective didactic elements