The purpose of this report is to describe the international growth, outcomes, complications and technology used in pediatric extracorporeal life support (ECLS) from 2009 to 2015 as reported by participating centers in the Extracorporeal Life Support Organization (ELSO). To date, there are 59,969 children who have received ECLS in the ELSO Registry; among those, 21,907 received ECLS since 2009 with an overall survival to hospital discharge rate of 61%. In 2009, 2,409 ECLS cases were performed at 157 centers. By 2015, that number grew to 2,992 cases in 227 centers, reflecting a 24% increase in patients and 55% growth in centers. ECLS delivered to neonates (0–28 days) for respiratory support was the largest subcategory of ECLS among children <18 years old. Overall, 48% of ECLS was delivered for respiratory support and 52% was for cardiac support or extracorporeal life support to support cardiopulmonary resuscitation (ECPR). During the study period, over half of children were supported on ECLS with centrifugal pumps (51%) and polymethylpentene oxygenators (52%). Adverse events including neurologic events were common during ECLS, a fact that underscores the opportunity and need to promote quality improvement work.

Background Necrotising enterocolitis (NEC) is one of the most common and fatal intestinal disorders in preterm infants. Breast-fed infants are at lower risk for NEC than formula-fed infants, but the protective components in human milk have not been identified. In contrast to formula, human milk contains high amounts of complex glycans. Objective To test the hypothesis that human milk oligosaccharides (HMO) contribute to the protection from NEC. Methods Since human intervention studies are unfeasible due to limited availability of HMO, a neonatal rat NEC model was used. Pups were orally gavaged with formula without and with HMO and exposed to hypoxia episodes. Ileum sections were scored blindly for signs of NEC. Two-dimensional chromatography was used to determine the most effective HMO, and sequential exoglycosidase digestions and linkage analysis was used to determine its structure. Results Compared to formula alone, pooled HMO significantly improved 96-hour survival from 73.1% to 95.0% and reduced pathology scores from 1.98±1.11 to 0.44±0.30 (p<0.001). Within the pooled HMO, a specific isomer of disialyllacto-N-tetraose (DSLNT) was identified to be protective. Galacto-oligosaccharides, currently added to formula to mimic some of the effects of HMO, had no effect. Conclusion HMO reduce NEC in neonatal rats and the effects are highly structure specific. If these results translate to NEC in humans, DSLNT could be used to prevent or treat NEC in formula-fed infants, and its concentration in the mother’s milk could serve as a biomarker to identify breast-fed infants at risk of developing this disorder.

Although enterocytes are capable of innate immune responses, the intestinal epithelium is normally tolerant to commensal bacteria. To elucidate the mechanisms of tolerance, we examined the effect of preexposure to LPS on activation of p38, c-Jun, and NF-κB in enterocytes by several inflammatory and stress stimuli. Shortly after the initial LPS challenge, enterocytes become tolerant to restimulation with LPS or CpG DNA, but not with IL-17 or UV. The state of tolerance, which lasts 20–26 h, temporally coincides with LPS-induced expression of the anti-inflammatory ubiquitin-editing enzyme A20. Small interfering RNA silencing of A20 prevents tolerance, whereas ectopic expression of A20 blocks responses to LPS and CpG DNA, but not to IL-17 or UV. A20 levels in the epithelium of the small intestine are low at birth and following gut decontamination with antibiotics, but high under conditions of bacterial colonization. In the small intestine of adult rodents, A20 prominently localizes to the luminal interface of villus enterocytes. Lower parts of the crypts display relatively low levels of A20, but relatively high levels of phospho-p38. Gut decontamination with antibiotics reduces the levels of both A20 and phospho-p38. Along with the fact that A20-deficient mice develop severe intestinal inflammation, our results indicate that induction of A20 plays a key role in the tolerance of the intestinal epithelium to TLR ligands and bacteria.

Necrotizing Enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. Although the inciting events leading to NEC remain elusive, various risk factors including prematurity, hypoxemia, formula feeding and intestinal ischemia have been implicated in the pathogenesis of NEC. Data from our lab and others suggest that NEC evolves from disruption of the intestinal epithelial barrier, as a result of a combination of local and systemic insults. We postulate that nitric oxide (NO), an important second messenger and inflammatory mediator, plays a key role in intestinal barrier failure seen in NEC. Nitric oxide and its reactive nitrogen derivative, peroxynitrite, may affect gut barrier permeability by inducing enterocyte apoptosis (programmed cell death) and necrosis, or by disrupting tight junctions or gap junctions that normally play a key role in maintaining epithelial monolayer integrity. Intrinsic mechanisms that serve to restore monolayer integrity following epithelial injury include enterocyte proliferation, epithelial restitution via enterocyte migration, and re-establishment of cell contacts. This review focuses on the biology of NO and the mechanisms by which it promotes epithelial injury while concurrently disrupting the intrinsic repair mechanisms. INDEX WORDSNecrotizing Enterocolitis; Nitric Oxide; Intestinal inflammation; Intestinal restitution Necrotizing Enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. The incidence of NEC approaches 1 per 1000 live-births, with approximately 1 out of 7 affected neonates succumbing to the disease 1 . The mortality rate

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