Neurogastroenterology and motility (NGM) disorders are common in childhood and are often very debilitating. Although pediatric gastroenterology fellows are expected to obtain training in the diagnosis and management of patients with these disorders, there is an ongoing concern for unmet needs and lack of exposure and standardized curriculum. In the context of tailoring training components, outcome and expressed needs of pediatric gastroenterology fellows and programs, members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and American Neurogastroenterology and Motility Society (ANMS) developed guidelines for NGM training in North America in line with specific expectations and goals of training as delineated through already established entrustable professional activities (EPAs). Members of the joint task force applied their expertise to identify the components of knowledge, skills, and management, which are expected of NGM consultants. The clinical knowledge, skills and management elements of the NGM curriculum are divided into domains based on anatomic regions including esophagus, stomach, small bowel, colon and anorectum. In addition, dedicated sections on pediatric functional gastrointestinal (GI) disorders, research and collaborative approach, role of behavioral health and surgical approaches to NGM disorders and transition from pediatric to adult neurogastroenterology are included in this document. Members of the NASPGHAN-ANMS task force anticipate that this document will serve as a resource to break existing barriers to pursuing a career in NGM and provide a framework towards uniform training expectations at 3 hierarchical tiers corresponding to EPA levels.
Background & Aims: RET receptor tyrosine kinase is necessary for enteric nervous system (ENS) development. Loss-of-function RET mutations cause Hirschsprung disease (HSCR), in which infants are born with aganglionic bowel. Despite surgical correction, HSCR patients often experience chronic defecatory dysfunction and enterocolitis, suggesting that RET is important after development. To test this hypothesis, we determined the location of postnatal RET and its significance in gastrointestinal (GI) motility. Methods: RetCFP/+ mice and human transcriptional profiling data were studied to identify the enteric neuronal and epithelial cells that express RET. To determine whether RET signaling in these cells regulates adult gut motility in vivo, genetic and pharmacologic approaches were used to disrupt RET in either all RET-expressing cells, a major subset of enteric neurons, or intestinal epithelial cells. Results: Distinct subsets of enteric neurons and enteroendocrine cells expressed RET in the adult intestine. RET disruption in the intestinal epithelium, rather than in enteric neurons, slowed GI motility selectively in adult male mice. This effect was phenocopied by RET kinase inhibition. Most RET+ epithelial cells were either enterochromaffin cells that release serotonin (5-HT) or L-cells that release peptide YY (PYY), both of which can alter motility. RET kinase inhibition exaggerated PYY release in a nutrient-dependent manner without altering 5-HT secretion. PYY receptor blockade fully rescued dysmotility in mice lacking epithelial RET. Conclusion: RET signaling normally limits nutrient-dependent PYY release from L-cells and this activity is necessary for normal intestinal motility in male mice. These effects could contribute to post-operative dysmotility in HSCR, which predominantly affects males, and uncovers a mechanism that could be targeted to treat post-prandial GI dysfunction.
Goal: The goal of this study was to characterize the etiology and demographics of hospitalized patients with gastroparesis (Gp) across different age groups. Background: Gp is a chronic condition associated with increasing hospitalizations and costs. The gender and etiology distributions of Gp throughout the age spectrum are unknown. Materials and Methods: Nationwide Inpatient Sample (NIS) and Kid’s Inpatient Database (KID) were used to identify patients using International Classification of Diseases (ICD)-10 codes for Gp as a primary diagnosis or as secondary diagnosis with the first diagnosis a GI-related symptom. Results: There were a total of 15,790 admissions (75.6% female, age: 46.2±18.0 y). After age 6, female admissions percentage increased: ages 2 to 5: 45.0%, ages 6 to 12: 62.8%, ages 13 to 20: 76.7% (P<0.001), with a distinct increase at age 12. Diabetic gastroparesis (DG) was seen in 3995 (25.3%) of all Gp admissions but in only 1.1% of children under the age of 20. Overall, 68% of DG admissions were female, but a higher percentage of DG was seen among male admissions for Gp compared with female admissions for Gp between ages 21 and 64 (38.3% vs. 23%, P<0.001). The most common races were white (63.2%), African American (20.6%), and Hispanic (8.7%). DG was more often present in Native American (61.9%), Hispanic (39.1%), and African American (38.2%) admissions than in white patients (17.8%; P<0.05). Conclusions: This study using large inpatient databases shows that the gender, race, and etiology of Gp admissions is age-dependent. The female predominance of Gp admissions is more prominent from the second decade of life. DG, although uncommon in children, is seen more often in nonwhite admissions.
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