Objective To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation (ITx) era. Study design The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multi-center cohort of infants with IF. Entry criteria included infants <12 mo receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as (n, %). Results 272 infants with a gestational age of 34 wks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 mo (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and PPIs (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1,000 catheter days. The cumulative incidences for enteral autonomy, death, and ITx were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the 5th year after study entry. Conclusions Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality and need for transplantation.

SummaryHuman intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine. Our study also revealed that the intestinal stem cell marker OLFM4 is expressed at very low levels in fetal intestine and in HIOs, but is robust in adult crypts. We validated our findings using in vivo transplantation to show that HIOs become more adult-like after transplantation. Our study emphasizes important maturation events that occur in the intestine during human development and demonstrates that HIOs can be used to model fetal-to-adult maturation.

To date, this report represents the largest series of patients undergoing the 1-stage transanal Soave pullthrough. This approach is safe, permits early feeding, causes minimal pain, facilitates early discharge, and presents a low rate of complications.

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