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Background & Aims: Perianal fistulizing Crohn's disease (PCD) is a common and debilitating complication with elusive pathophysiology. We examined mucosal cells from patients with PCD and related conditions using a multi-omics approach., Methods: We recruited patients with PCD (n = 24), CD without perianal disease (NPCD, n = 10), and idiopathic perianal fistulas (IPF, n = 29). Biopsies were taken from fistula tracts, fistula opening, and rectal mucosa. Single-cell RNA-sequencing (scRNA-seq), mass cytometry (CyTOF), spatial transcriptomics (ST), immunohistochemistry, and integrated analysis were performed., Results: ScRNA-seq, CyTOF, and ST unraveled immune and non-immune cell compartments in PCD and IPF fistula tracts. PCD fistulas showed hyperactivated pathogenic pathways including interferon (IFN)G response and TNF signaling in myeloid and stromal cells. Intestinal cells from PCD patients also expressed greater levels of IFNG-responsive and EMT genes compared to NPCD patients. Furthermore, both fistula tracts and ileal mucosa from PCD patients harbored expanded IFNG+ pathogenic Th17 cells, which expressed elevated inflammatory mediators. CyTOF also identified skewed immune cell phenotypes in the fistula tracts, fistula opening, and rectum in PCD patients including expanded Th17 cells, increased pathogenic myeloid cells, and altered T cell exhaustion markers. Further analysis also revealed cellular modules associated with anti-TNF therapy in PCD patients., Conclusion: Multi-omics analysis revealed immune, stromal, and epithelial cell landscapes of PCD, which highlight the pathogenic role of hyperactivated IFNG signaling in both fistula tracts and luminal mucosa. This study identified IFNG as a potential therapeutic target for PCD.

Background: Chronic idiopathic constipation (CIC) is a substantial problem in pediatric and adult patients with similar symptoms and workup; however, surgical management of these populations differs. We systematically reviewed the trends and outcomes in the surgical management of CIC in pediatric and adult populations., Methods: A literature search was performed using Ovid MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov between January 1, 1995 and June 26, 2020. Clinical trials and retrospective and prospective studies of patients of any age with a diagnosis of CIC with data of at least 1 outcome of interest were selected. The interventions included surgical resection for constipation or antegrade continence enema (ACE) procedures. The outcome measures included bowel movement frequency, abdominal pain, laxative use, satisfaction, complications, and reinterventions., Results: Adult patients were most likely to undergo resection (94%), whereas pediatric patients were more likely to undergo ACE procedures (96%) as their primary surgery. Both ACE procedures and resections were noted to improve symptoms of CIC; however, ACE procedures were associated with higher complication and reintervention rates., Conclusion: Surgical management of CIC in pediatric and adult patients differs with pediatric patients receiving ACE procedures and adults undergoing resections. The evaluation of resections and long-term ACE data in pediatric patients should be performed to inform patients and physicians whether an ACE is an appropriate procedure despite high complication and reintervention rates or whether resections should be considered as an initial approach for CIC., (Copyright © 2023 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)