Background:Perianal Crohn's disease (PCD) represents one of the most severe and refractory forms of pediatric inflammatory bowel disease (IBD). Constipation and colonic redundancy, particularly type 1 dolichocolon (T1-DC), may increase distal rectosigmoid pressure, and exacerbate perianal pathology. We hypothesized that T1-DC is more common in children with PCD than in those with uncomplicated ileocolonic Crohn's disease (CD) or non-IBD controls. Methods:We retrospectively analyzed 20 consecutive pediatric PCD cases (penetrating [B3p] or inflammatory [B1p]) and compared them with 20 patients with non-complicated ileocolonic CD (L3/B1) and 30 non-IBD trauma controls. DC type was determined radiographically using established criteria, focusing on T1- and T2-DC. Constipation history was abstracted from medical records under IRB-approved protocols. Results:DC was significantly more prevalent in PCD than in ileocolonic CD or controls (p < 0.001), primarily due to T1-DC. The associations persisted (p<0.03) in PCD patients without a history of constipation. Conclusions:Rectosigmoid redundancy (T1-DC) may represent an underrecognized anatomic co-morbidity in pediatric PCD, contributing to increased distal pressure and susceptibility to perianal complications. Identification of T1-DC could inform surgical decision-making and postoperative management. Targeted approaches-such as segmental resection during stoma reversal, structured bowel regimens, physical activity, and pelvic-floor biofeedback-may help reduce recurrence risk. Prospective studies are needed to define the mechanistic role of colonic redundancy in the pathogenesis of PCD.

What's Known The association between tumor necrosis factor antagonist and eosinophilic gastrointestinal disorders, including eosinophilic esophagitis is reported. There is a potential association between the initiation of IFX therapy for some IBD patients and the subsequent development of EoE. What's New This case series of IBD patients who developed eosinophilic esophagitis post‐infliximab (IFX) therapy, highlights their demographic characteristics, clinical features, and comorbidities. IFX might trigger a Th2 cytokine shift, leading to eosinophilic infiltration. Long‐term safety data are needed to identify outcomes in patients who develop eosinophilic esophagitis after treatment with TNF‐alpha antagonists.

We present a case of a female with complex pediatric-onset stricturing small bowel and colonic Crohn's disease. She was refractory to multiple advanced therapies, requiring dual therapy with risankizumab and upadacitinib to induce healing. Using intestinal ultrasound to monitor her response to therapy, we ultimately de-escalated to risankizumab monotherapy due to a reduction of inflammatory burden. We present this case to highlight the use and importance of intestinal ultrasound to guide changes in therapy, discussing its use in practice for patients with inflammatory bowel disease.

Pediatric-onset inflammatory bowel diseases (IBD) are associated with an elevated risk of venous thromboembolism (VTE). However, data on the VTE risk in these patients treated with novel biologics, particularly vedolizumab, remain limited. To evaluate the association between vedolizumab and the risk of VTE compared with other biologics in patients with pediatric-onset Crohn’s disease (CD) or ulcerative colitis (UC). We emulated a target trial using electronic health records from the TriNetX research network. The study included patients with CD or UC diagnosed before the age of 18 years who were treated with vedolizumab, ustekinumab, or anti-tumor necrosis factor (TNF) agents. Comparative groups were generated using 1:1 propensity-score matching based on relevant confounders. The primary outcome was the occurrence of any VTE within 12 months of follow-up. Cox proportional hazards models were used to compare the risk of VTE between vedolizumab-treated patients and those treated with anti-TNF agents and ustekinumab. A total of 1806 matched patient pairs were analyzed across four comparisons: patients treated with vedolizumab versus anti-TNF agents (CD = 407 pairs; UC = 443 pairs), and vedolizumab versus ustekinumab (CD = 563 pairs; UC = 393 pairs), respectively. Patients with CD receiving vedolizumab had a significantly higher risk of VTE compared with those receiving anti-TNF therapy (hazard ratio [HR] 8.63; 95

Abstract Background DEVELOP is a multi-center, global, prospective, observational, longitudinal registry of long-term safety of infliximab (and other treatments) in paediatric patients (pts) with inflammatory bowel disease (IBD) <18 years (yrs) at diagnosis. Over the course of follow-up, many pts required changes in therapy. Ustekinumab (UST) is approved for treatment of Crohn’s disease (CD) in adults and is currently being evaluated for safety/efficacy in paediatric pts. This report focuses on assessment of safety of UST in paediatric pts with CD from DEVELOP. Methods Data included paediatric pts treated with UST from 31 May 2007 through 30 June 2022; data are collected every 6 months. The analyzed population included: all paediatric pts (all pts), pts weighing <40kg (<40kg group), and pts weighing ≥40kg (≥40kg group). Assessments included medical and treatment history, UST exposure, adverse events (AEs), serious AEs (SAEs), CD-related SAEs leading to hospitalization, IBD surgeries, serious and opportunistic infections, malignancies, and deaths. Results A total of 150 pts received UST (49.3% females); 31 in the <40kg group and 119 in the ≥40kg group (Table 1). Most treated pts (92.0%) were 12-17yrs. The majority (91%) of pts were initially dosed with UST every 8 weeks (q8w); at the last known dose, 64% received UST q8w and 22% q4w. Mean (SD) age of initial UST exposure was 15yrs (2.19). Prior IBD surgery was reported in 65.3% pts. The majority of pts (98%) had prior biologic therapy and 72% received ≥2 biologics prior to UST. Overall, 37/150 (24.7%) of pts discontinued UST during follow-up, with a mean (SD) time to discontinuation of 16.7 (17.00) months; 84/150 (56.0%) were exposed to UST for ≥24 months. Rates (events/100 pt-yrs) of AEs were higher in the ≥40kg group (177.62) than in the <40kg group (101.27). Rates of SAEs were slightly lower among the ≥40kg group (25.42) vs <40kg (32.67). There were no SAEs related to infusion or injection site reactions. Rates of serious infections and CD-related hospitalizations were low and similar between groups, and rates of IBD-related surgeries were similar between groups (Figure 1). One malignancy (malignant carcinoid tumor) was reported in a female (18yrs) in the ≥40kg group with a history of prior therapy with vedolizumab, methotrexate, and 6-MP. No deaths or opportunistic infections were reported. Conclusion The safety profile observed for this off-label use of UST in paediatric CD pts in DEVELOP was similar to that of the treated adult population, despite most paediatric pts having prior biologic exposure. No new safety signals are identified in this paediatric population.

ObjectivesDiacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN.MethodsFrom 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life.ResultsAll patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN.ConclusionsChildren with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency. What is Known Homozygous DGAT1 deficiency causes congenital diarrhea/intestinal failure associated with protein-losing enteropathy. Affected infants are often dependent on total parenteral nutrition (TPN) in early life.What is New DGAT1 deficient patients treated with ultra-low-fat formula and periodic peripheral intravenous lipid supplementation maintained normal growth and development. Triene:tetraene ratios were consistent with essential fatty acid status. In infants with DGAT1 deficiency, ultra-low-fat formula coupled with periodic peripheral intravenous lipid supplementation prevents the need for prolonged TPN, while maintaining adequate growth and essential fatty acid status as well as achieving enteral autonomy.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. When a child is diagnosed with both PSC and inflammatory bowel disease (IBD), evidence-based information on counseling families and risk management of developing cholangiocarcinoma is limited. In this case series (PubMed/collaborators), we included patients with PSC-IBD who developed cholangiocarcinoma and contacted authors to determine an event curve specifying the time between the second diagnosis (IBD or PSC) and a diagnosis of cholangiocarcinoma. Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric-onset PSC-IBD-cholangiocarcinoma. The median time to development of cholangiocarcinoma was 6.95 years from the second diagnosis. Despite the small number, 38% of cholangiocarcinoma developed within the first 2 years, and 47% of patients developed cholangiocarcinoma in the transition period to adult care (age 14-25). Our findings highlight the importance of screening that extends over the so-called transition period from pediatric to adult care.

Abstract Background While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of reliable, highly accurate, non-invasive biomarkers that differentiate CD and UC in pediatric IBD are an unmet need of paramount importance in terms of medical care, surgical intervention, and prognosis. The most advanced proteomics technology, the aptamer-based SomaScan, enables measurement of 11,000 biologically relevant proteins, including very low abundant proteins, and was tested to discover serum protein biomarkers capable of differentiating between pediatric CD and UC. Methods SomaScan (SomaLogic; Boulder, CO) quantitative serum protein profiles were generated from pediatric subjects diagnosed with CD (n=56) and UC (n=25) using standard diagnostic criteria. The disease location for patients with CD was 18 L1 (ileal), 9 L2 (colonic), 27 L3 (ileo-colonic) and 2 L4 (small bowel); Inflammatory phenotype (B1) occurred in 40, stricturing (B2) in 8, penetrating (B3) in 6, and B2B3 in 2. To develop highaccuracy predictors with the lowest number of proteins for discriminating CD from UC, we used machine learning and conditional logistic regression to calculate odds ratios(OR) and 95% confidence intervals(CI) per one standard deviation increase in protein levels. Area under the curve (AUC) was calculated to determine the performance of the multi-protein model in discriminating CD cases from UC cases. Ingenuity pathway analysis was conducted to identify pathophysiological pathway differences between CD and UC. Results There were 256 proteins that were discriminating between CD and UC with fold change >1.3 and an unadjusted p-value <0.05. Of these, 38 proteins were associated with increased odds and 218 proteins were associated with decreased odds of CD diagnosis. Compared to UC, CD cases had decreased neutrophil movement and degranulation, inflammatory response, and metabolism of reactive oxygen species but enhanced apoptosis. When we developed a multi-protein model and assessed its performance to discriminate CDs cases from UC cases, a 4-protein model showed an AUC=0.97. Conclusion Using the most comprehensive proteomics platform, we identified serum proteins and developed a high accuracy multi-protein model discriminating between pediatric CD and UC. The utility of SomaScan demonstrates not only the value of these diagnostic biomarkers, but also the potential to discover immune and metabolic pathways that distinguish CD from UC.

Objectives: Children on the autism spectrum disorder (ASD) may express pain or discomfort through stereotypic or self-injurious behaviors. Gastroesophageal reflux disease (GERD) may be challenging to diagnose in a child who is non-verbal or has impaired communication skills, diagnostic testing for GERD may be the only way to establish the diagnosis. We report our experience using the BRAVO wireless pH monitoring device for the evaluation of GERD in this patient population. Methods: Tolerance and feasibility as well as pH parameters and symptom correlation of the BRAVO pH were evaluated retrospectively in ASD children and compared it to a large cohort of non-ASD children. Only patients with studies lasting >24 hours were included. Results: A total of 172 patients were included, 27 of those were diagnosed with autism (median age 11 years, 17 male). We found no difference in age and weight between both groups but there was a male predominance in the autism group (P = 0.007). We found no difference in the ability to complete at least 24 hours of study duration between both groups (24/27 or 89% in ASD vs 133/145 or 92% non-ASD patients, P = 0.632). We also found no difference in the median reflux index on the worst day (P = 0.27) or the average of both days (P = 0.75), BRAVO pH parameters and the proportion of abnormal studies between ASD and non-ASD children. When evaluating the overall symptom correlation with GER episodes, we did not find a difference between both groups, but we did find a higher symptom correlation for GER symptom during supine position in ASD children. Study was performed for behavioral indication in 11 ASD children, all had normal esophageal mucosa but 4 of those had an abnormal BRAVO pH study. No significant side effects were reported during the study, only 2 patients (1 non-ASD and 1 ASD) complained of self-limited chest pain. Conclusions: BRAVO wireless pH is well tolerated and feasible in evaluating GER and behavioral symptoms in ASD children and provides a reasonable alternative to standard trans-nasal pH monitoring.

Background and Aims: Collagenous gastritis (CG) is a rare disorder characterized by increased subepithelial collagen deposition and inflammatory infiltrates. The mechanisms involved in CG pathogenesis are poorly understood, and no CG-associated biomarkers have been identified. This proteomics study identified serum biomarkers and pathogenic pathways to provide new knowledge about the pathobiology of CG, a disease reported in less than 100 patients. Methods: Nine serum samples from pediatric patients diagnosed with CG were evaluated using novel aptamer-based proteomic technology and systems biology to generate new knowledge about the complex interactions between the differentially expressed proteins and candidate upstream regulators, using the Ingenuity Pathway Analysis in patients with non-CG and patients with normal gastric biopsies or nongastritis (NG). Results: SOMAscan analysis identified 63 proteins significantly dysregulated in CG as compared to non-CG or NG patients that converged around enhanced inflammatory response and immune cell migration but reduced vascular functions. Principal component analysis using 15 of those proteins accurately separated the CG cases from the 2 comparator control groups. Using immunoassays, serum epidermal growth factor concentrations in CG patients, a protein involved in collagen production, were confirmed to be significantly lower than those in gastritis/NG patients. Conclusion: This is the first comprehensive analysis of the proteome in CG patients that reveals metabolic pathways relating inflammation and fibrosis as well as a new potential role of epidermal growth factor as a disease biomarker.

Construction of an ileal pouch–anal anastomosis, also known as a J-pouch, is the operation of choice for most cases of refractory ulcerative colitis (UC) and is associated with improved health-related quality of life and patient satisfaction.1 Despite these potential benefits, an increase in infertility by up to 3-fold is one potential surgical consequence of an open J-pouch procedure, likely owing to tubal occlusions and pelvic adhesion formation.2 Ensuring that female patients with refractory UC are provided with adequate information to make informed personal decisions about surgical options is of critical importance. Investigation of the specific recommendations made by health care providers concerning J-pouch surgery will allow for the identification of knowledge gaps and encourage an increase in collaboration and education amongst the various medical specialties engaged in care for female patients with inflammatory bowel disease (IBD). In this study, we aimed to assess health care providers’ general knowledge...

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn’s disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation. Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

AbstractGenome-wide association studies (GWAS) have identified hundreds of loci associated with Crohns disease (CD), however, as with all complex diseases, deriving pathogenic mechanisms from these non-coding GWAS discoveries has been challenging. To complement GWAS and better define actionable biological targets, we analysed sequenced data from more than 30,000 CD patients and 80,000 population controls. We observe rare coding variants in established CD susceptibility genes as well as ten genes where coding variation directly implicates the gene in disease risk for the first time.