Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH

Innate Immune Deficiency of Extremely Premature Neonates Can Be Reversed by Interferon-γ

Background: Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants. Methodology/Principal Findings: We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Grampositive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-c. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-c. Conclusion/Significance: Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressivel

Interleukin-7 Influences FOXP3+CD4+ Regulatory T Cells Peripheral Homeostasis

Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance

Optimal level of nasal continuous positive airway pressure in severe viral bronchiolitis

Abstract Purpose: To determine the optimal level of nasal continuous positive airway pressure (nCPAP) in infants with severe hypercapnic viral bronchiolitis as assessed by the maximal unloading of the respiratory muscles and improvement of breathing pattern and gas exchange. Methods: A prospective physiological study in a tertiary paediatric intensive care unit (PICU). Breathing pattern, gas exchange, intrinsic end expiratory pressure (PEEPi) and respiratory muscle effort were measured in ten infants with severe hypercapnic viral bronchiolitis during spontaneous breathing (SB) and three increasing levels of nCPAP. Results: During SB, median PEEPi was 6 cmH 2 O (range 3.9-9.2 cmH 2 O), median respiratory rate was 78 breaths/min (range 41-96), median inspiratory time/total duty cycle (T i /T tot ) was 0.45 (range 0.40-0.48) and transcutaneous carbon dioxide pressure (P tc CO 2 ) was 61.5 mmHg (range 50-78). In all the infants, an nCPAP level of 7 cmH 2 O was associated with the greatest reduction in respiratory effort with a mean reduction in oesophageal and diaphragmatic pressure swings of 48 and 46%, respectively, and of the oesophageal and diaphragmatic pressure time product of 49 and 56%, respectively. During nCPAP, median respiratory rate decreased to 56 breaths/min (range 39-108, p \ 0.05), median T i /T tot decreased to 0.40 (range 0.34-0.44, p \ 0.50) and P tc CO 2 decreased to 49 mmHg (range 35-65, p \ 0.05). Only one infant with associated bacterial pneumonia required intubation and all the infants were discharged alive from the PICU after a median stay of 5.5 (range 3-27 days). Conclusion: In infants with hypercapnic respiratory failure due to acute viral bronchiolitis, an nCPAP level of 7 cmH 2 O is associated with the greatest unloading of the respiratory muscles and improvement of breathing pattern, as well as a favourable short-term clinical outcome. Keywords Nasal continuous positive airway pressure Á Intrinsic positive end expiratory pressure Á Bronchiolitis Á Work of breathing Á Childre