BackgroundGlucagon‐like peptide‐2 (GLP‐2) is an intestinotrophic factor released from L‐cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP‐2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long‐acting GLP‐2 analogue, FE 203799 (FE; apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum.MethodsNeonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair‐fed parenteral and enteral nutrition. Saline and FE (5 mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24‐hour fecal samples were collected for subsequent nutrient analysis. On day 7, small‐intestinal length and weight were measured and tissue collected for analyses.ResultsOn day 7, saline and FE‐treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE‐treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small‐intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054).ConclusionsThe subcutaneous GLP‐2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP‐2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.

Objectives: Short bowel syndrome (SBS) remains the leading cause of neonatal intestinal failure. Milk fat globule epidermal growth factor-8 (MFG-E8), present in human milk, has homology with epidermal growth factor (EGF), known to enhance adaptation in SBS. In this pilot study, the role of oral MFG-E8 treatment in SBS was explored in neonatal piglets. Methods: Neonatal piglets underwent 75% intestinal resection, either distal (jejunal-colonic [JC] anastomosis) or mid-intestinal (jejunal-ileal [JI] anastomosis). Piglets were randomized to intragastric treatment with MFG-E8  (5 mg/kg per day) or saline and were maintained on parenteral nutrition and enteral nutrition for 7 days. Adaptation was assessed by intestinal length and weight, histopathology, fecal fat analysis and RT-qPCR analysis of mucosal transcripts, including growth factors. Results: JI piglets demonstrated intestinal lengthening (P < 0.001), 2-fold greater in ileum than jejunum (P  = 0.02), where lengthening was increased by MFG-E8 treatment (P = 0.02). JC piglets did not exhibit jejunal lengthening, regardless of treatment. Fat absorption was greater for JI piglets (P = 0.02), unaffected by treatment. In JI piglets, expression of Egf was increased in the ileum (P < 0.01) and MFG-E8 treatment increased Egfr (receptor) expression (P = 0.02). Conclusions: MF-EG8 demonstrated site-specific trophic effects, only with JI anatomy. This may limit the utility of this treatment for SBS, except for rare patients with retained ileum. The mechanisms of these site-specific effects, however, and the role of MFG-E8 in neonatal gut growth and in diseases, such as necrotizing enterocolitis that commonly target ileum, warrant further exploration.

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Background Pain is one of the most common symptoms encountered in the healthcare system, and opioids are among the top three medications used to treat it. Understanding the reasoning behind physicians’ opioid prescribing practices is vital to safe practice. The primary objective of our study was to describe pediatric emergency physicians’ decision-making process when prescribing opioids for children’s acute pain management. Methods This study employed qualitative methodology, using one-on-one semi-structured interviews within a grounded theory analytic framework. We employed purposeful sampling to recruit pediatric emergency physicians from across Canada. Interviews were conducted by telephone (December 2019–January 2021). Transcript analysis occurred concurrently with data collection, supporting data saturation and theory development considerations. Results Eleven interviews were completed with participants representing each of Canada’s geographic regions. Nine major themes emerged: (1) practice setting and outpatient opioid use, (2) condition-specific considerations, (3) physician confidence in medical evidence, (4) pain assessment challenges, (5) patient and family perspectives, (6) opioid safety concerns, (7) personal biases and experiences, (8) personal practice context, and (9) the Opioid Crisis/media influence. Most clinicians felt that they limited opioid use to those who needed it most; all participants described challenges managing acute pain, emphasizing the need for accurate pain measurement and better guidelines, evidence-based data, and knowledge translation. Clinicians were more comfortable treating pain in the emergency department, compared to discharge prescribing. They recognized the importance of co-therapy with non-opioids and the need for opioid risk assessment when prescribing. A family centered approach was recognized as the goal of practice. Conclusion Clinicians are less comfortable prescribing opioids to children for at-home use and find pain assessment and lack of clear guidelines to be barriers to pain care. Knowledge translation strategies for safer practice and optimal acute pain management could support responsible and judicious opioid use.