Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis.

Autor:	Hyams JS; Connecticut Children's Medical Center, Hartford, Connecticut, USA., Brimacombe M; Connecticut Children's Medical Center, Hartford, Connecticut, USA., Haberman Y; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.; Sheba Medical Center, Tel-HaShomer, affiliated with Tel-Aviv University, Ramat Gan, Israel., Walters T; Hospital for Sick Children, Toronto, Ontario, Canada., Gibson G; Georgia Tech University, Atlanta, Georgia, USA., Mo A; Georgia Tech University, Atlanta, Georgia, USA., Mack D; Children's Hospital of Eastern Ontario and Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada., Griffiths A; Hospital for Sick Children, Toronto, Ontario, Canada., Boyle B; Nationwide Children's Hospital, Columbus, Ohio, USA., LeLeiko N; Hasbro Children's Hospital, Providence, Rhode Island, USA., Markowitz J; Cohen Children's Medical Center, Queens, New York, USA., Rosh J; Goryeb Children's Hospital, Morristown, New Jersey, USA., Patel A; Texas Children's Hospital, Houston, Texas, USA., Shah S; Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA., Baldassano R; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Pfefferkorn M; Riley Children's Hospital, Indianapolis, Indiana, USA., Sauer C; Emory University, Atlanta, Georgia, USA., Dailey J; Connecticut Children's Medical Center, Hartford, Connecticut, USA., Venkateswaran S; Emory University, Atlanta, Georgia, USA., Kugathasan S; Emory University, Atlanta, Georgia, USA., Denson LA; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Inflammatory bowel diseases [Inflamm Bowel Dis] 2022 Feb 01; Vol. 28 (2), pp. 151-160.
DOI:	10.1093/ibd/izab061
Abstrakt:	Background: Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). Methods: This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. Results: Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). Conclusions: A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies. (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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