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

Hyams, Jeffrey S.; Brimacombe, Michael; Haberman, Yael; Walters, Thomas D.; Gibson, Greg; Mo, Angela; Mack, David R.; Griffiths, Anne M.; Boyle, Brendan; Leleiko, Neal S.; Markowitz, James; Rosh, Joel R.; Patel, Ashish; Shah, Sapana; Baldassano, Robert N.; Pfefferkorn, Marian D.; Sauer, Cary G.; Dailey, Joelynn; Venkateswaran, Suresh; Kugathasan, Subra; Denson, Lee A.

doi:10.1093/ibd/izab061

Cited by 17 publications

(6 citation statements)

References 30 publications

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“…The PROTECT UC inception cohort was designed to examine factors associated with baseline disease severity and with responses to standardized therapy and to highlight mucosal signals and genes that are linked with nonresponse to therapy. In PROTECT, UC was clinically and endoscopically graded at baseline, and disease course was recorded prospectively after standardized initial therapy with mesalamine or corticosteroids (21,30,31) (Figure 4A and Supplemental Table 2). Focusing on the protein-coding genes in PROTECT, we previously reported a profound suppression of mitochondrial genes and function across cohorts in active UC (21), and we defined genes and pathways linked to UC early and late course (21,30,31).…”

Section: Resultsmentioning

confidence: 99%

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn’s disease, and celiac disease

Braun¹,

Sosnovski²,

Almasi‐Hashiani³

et al. 2023

JCI Insight

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Ulcerative colitis (UC), Crohn's disease (CD), and celiac disease are prevalent intestinal inflammatory disorders with nonsatisfactory therapeutic interventions. Analyzing patient data-driven cohorts can highlight disease pathways and new targets for interventions. Long noncoding RNAs (lncRNAs) are attractive candidates, since they are readily targetable by RNA therapeutics, show relative cell-specific expression, and play key cellular functions. Uniformly analyzing gut mucosal transcriptomics from 696 subjects, we have highlighted lncRNA expression along the gastrointestinal (GI) tract, demonstrating that, in control samples, lncRNAs have a more location-specific expression in comparison with protein-coding genes. We defined dysregulation of lncRNAs in treatment-naive UC, CD, and celiac diseases using independent test and validation cohorts. Using the Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) inception UC cohort, we defined and prioritized lncRNA linked with UC severity and prospective outcomes, and we highlighted lncRNAs linked with gut microbes previously implicated in mucosal homeostasis. HNF1A-AS1 lncRNA was reduced in all 3 conditions and was further reduced in more severe UC form. Similarly, the reduction of HNF1A-AS1 ortholog in mice gut epithelia showed higher sensitivity to dextran sodium sulfate-induced colitis, which was coupled with alteration in the gut microbial community. These analyses highlight prioritized dysregulated lncRNAs that can guide future preclinical studies for testing them as potential targets.

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Section: Resultsmentioning

confidence: 99%

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn’s disease, and celiac disease

Braun¹,

Sosnovski²,

Almasi‐Hashiani³

et al. 2023

JCI Insight

Self Cite

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“…As a rescue therapy, the guidelines also suggested cyclosporine or tacrolimus as a bridge to long-term maintenance therapy. In general, prompt referral for urgent colectomy is recommended following failure of one second-line medical therapy (5,12,17,18). As our patient presented with ASC refractory to conventional therapy and according to the guidelines, a colectomy was discussed with the surgical team.…”

Section: Discussionmentioning

confidence: 99%

Tofacitinib to Treat Severe Acute Refractory Colitis in a Teenager: Case Report and Review of the Literature

2022

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Objectives: Acute severe colitis (ASC) may occur within 3 months of ulcerative colitis diagnosis in 9%–15% of children and the rate of colectomy is up to 40%–50% within 5 years after an ASC. The aim of this publication is to present recent and relevant data on the success of medical treatment with tofacitinib in ASC. Methods: We report a challenging case of a teenage boy with ASC at diagnosis and conduct a discussion after a review of the literature regarding the use of tofacitinib in inflammatory bowel disease, especially in pediatric patients and in ASC. Results: The patient was hospitalized for 10 weeks and was refractory to conventional therapies: intravenous corticosteroids, infliximab, methotrexate, and vedolizumab. He received 7 blood transfusions and also presented with a severe malnutrition requiring a total parenteral nutrition. Tofacitinib was considered as a medical last resort before colectomy and was started at week 8. Thirteen days after starting tofacitinib, he was asymptomatic and was discharged on tofacitinib as sole treatment. By week 9 of tofacitinib, a colonoscopy showed both endoscopic and histological remission. He has remained in clinical remission at 6-month follow-up. Conclusions: Tofacitinib may be an alternative medical treatment to avoid colectomy in ASC. It is a small molecule with a rapid onset and few severe adverse events. It has been used for ASC in adult patients, allowing to avoid colectomy in more than 60%. To our knowledge, this is one of the few pediatric patients with refractory ASC at initial diagnosis who responded to tofacitinib.

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“…Although 13% to 14% of children with UC will require colectomy with currently available medical therapies, more than half of these surgeries will occur in hospitals that perform fewer than 2 colectomies per year. [1][2][3] The disease course of pediatric IBD is generally more aggressive, and there is an enrichment of genetic contribution in younger ages. 4,5 This systematic review summarizes diagnosing and managing pouch disorders in children.…”

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confidence: 99%

Diagnosis and Treatment of Pouch Disorders in Children: A Systematic Review

Nallapaneni,

Picoraro

2024

Diseases of the Colon &Amp; Rectum

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BACKGROUND: Restorative proctocolectomy and ileal pouch anal anastomosis has become the surgical procedure of choice in pediatric patients with medically-refractory ulcerative colitis or familial adenomatous polyposis. This systematic review aims to assess the diagnosis and treatment of pouch disorders in pediatric patients who undergo ileal pouch anal anastomosis. METHODS: A literature search was performed on MEDLINE, Google Scholar and EMBASE for all publications describing outcomes of pediatric ileal pouch anal anastomosis. Studies between January 1, 2000 and September 7, 2022 published in English were included. Studies were excluded based on title, abstract and full-length review. RESULTS: Thirty-three studies were included in this review, all of which were retrospective in nature. The outcomes of 2643 pediatric patients were included in the 33 studies. Pouch disorders described include anastomotic leaks, pouch strictures, pouch failure, pouchitis, cuffitis and de novo Crohn’s disease of the pouch. CONCLUSIONS: The reported incidence of disorders of the pouch in children varies widely and is likely attributable to differences in definitions and follow-up periods across studies. Pouchitis was the most frequently described outcome. The overall rate of pouch failure in children is relatively low with de novo Crohn’s disease of the pouch the most significant risk factor. Management is largely informed by clinical practices in adult patients with scant data on treatment efficacy in children. Multicenter, prospective studies are needed in the pediatric population in order to accurately identify risk factors, standardize the assessment of pouch complications, and determine effective treatment strategies. See 20-minute symposium video.

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

Cited by 17 publications

References 30 publications

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn’s disease, and celiac disease

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn’s disease, and celiac disease

Tofacitinib to Treat Severe Acute Refractory Colitis in a Teenager: Case Report and Review of the Literature

Diagnosis and Treatment of Pouch Disorders in Children: A Systematic Review

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