Development and Validation of the TUMMY-UC: A Patient-Reported Outcome for Pediatric Ulcerative Colitis.

BACKGROUND & AIMS: The TUMMY-UC is a patient-reported outcome measure for pediatric ulcerative colitis (UC) with an observer-reported outcome version for children aged <8 years. It includes eight items selected by concept elicitation interviews. We aimed to finalize the TUMMY-UC by cognitive interviews (stage 2) and to evaluate the index for its psychometric properties (stage 3). METHODS: The TUMMY-UC items were first finalized during 129 cognitive debriefing interviews. Then, in a prospective, multicenter validation study, 84 children who underwent colonoscopy or provided stool for calprotectin completed the TUMMY-UC and various measures of disease activity. Assessments were repeated after 7 and 21 days for evaluating reliability and responsiveness. RESULTS: During stage 2, the items were formatted with identical structure to ensure conceptual equivalence and weighted based on ranking of importance. In stage 3, the TUMMY-UC total score had excellent reliability in repeated assessments (intraclass correlation coefficient, 0.90; 95% confidence interval, 0.84-0.94). It also had moderate to strong correlations with all constructs of disease activity: r = 0.70 with UC endoscopic index of severity, r = 0.63 with the IMPACT-III questionnaire, r = 0.43 with calprotectin, r = 0.80 with the Pediatric Ulcerative Colitis Activity Index, r = 0.75 with global assessment of disease activity, and r = 0.46 with C-reactive protein (all P < .015). The index had excellent discrimination of disease activity, with a score of <9 defining remission (area under the receiver operating characteristic curve, 0.95; 95% confidence interval, 0.93-0.99). The ΔTUMMY-UC showed high responsiveness and differentiated well between children who experienced changed from those with no change. CONCLUSIONS: The TUMMY-UC, constructed from patient-reported outcome and observer-reported outcome versions, is a reliable, valid and responsive index that can be now used in practice and clinical trials.

Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

Comparing Gastrointestinal Endoscopy Findings in Children with Autism, Developmental Delay, or Typical Development.

OBJECTIVE: To compare endoscopic and histologic upper endoscopy (esophagogastroduodenoscopy [EGD]) findings in children with autism spectrum disorders (ASD) to age- and gender-matched controls with developmental delay (DD) or with typical development (TD). METHODS: Retrospective, cross-sectional study of children undergoing EGD, identifying those diagnosed with ASD, and matching on age and gender to children with DD or TD in ratio of 1:1:2. Rates of EGD findings were compared between the 3 groups using χ² or Fisher exact test. Multivariable linear regression was performed to identify predictors of abnormal histology. RESULTS: A total of 2104 patients were included (526 ASD; 526 DD; 1052 TD). Children with ASD had higher rates of abnormal esophageal histology (ASD 38.4%; DD 33.4%; TD 30.4%, P = .008), particularly esophagitis. In multivariable modeling, ASD diagnosis was an independent predictor of abnormal esophageal histology (OR [95% CI] 1.38 [1.09, 1.76]) compared with TD. Stomach findings did not differ among the groups. In the duodenum, histologic abnormalities were observed with lower frequency in ASD (ASD 17.0%; DD 20.1%; TD 24.2%, P = .005). In multivariable analysis, ASD diagnosis was not a significant predictor (OR 0.78 [0.56, 1.09]) of abnormal duodenal histology. CONCLUSIONS: Children with ASD have higher rates of histologic esophagitis compared with age- and gender-matched DD and TD controls. ASD was a significant independent predictor of abnormal esophageal, but not, duodenal, histology. These results underscore the importance of EGD in children with ASD.

Anti-infliximab antibodies and low infliximab levels correlate with drug discontinuation in pediatric inflammatory bowel disease.

BACKGROUND: Infliximab (IFX) use is limited by loss of response often due to the development of anti-IFX antibodies and low drug levels. METHODS: We performed a single center prospective observational cohort study of pediatric and young adult subjects with inflammatory bowel disease (IBD) on IFX with over 3 years of follow-up. Infliximab levels (IFXL) and antibodies to infliximab (ATI) were measured throughout the study. Subjects were followed until IFX was discontinued. RESULTS: We enrolled 219 subjects with IBD (184: Crohn's disease; 33: Ulcerative colitis; and 2 Indeterminant colitis; 84 female, median age 14.4 years, 37% on concomitant immunomodulator). Nine hundred and nineteen serum samples (mean 4.2 ± 2.1 per patient) were tested for IFXL and ATI. During the study, 31 (14%) subjects discontinued IFX. Sixty patients had ATI. Twenty-two of those 60 patients with ATI discontinued IFX; 14 of 31 patients who discontinued IFX had detectable ATI at study onset. The combination of ATI and IFXL < 5 µg/mL at study entry was associated with the highest risk of drug discontinuation (hazard ratios [HR] ATI 4.27 [p < 0.001] and IFXL < 5 µg/mL [HR]: 3.2 p = 0.001). Patients with IFXL 5-10 µg/mL had the lowest rate of discontinuation (6%). IFX dose escalation eliminated ATI in 21 of 60 subjects. CONCLUSIONS: ATI is a strong predictor of needing to stop IFX use and inversely correlates with IFXL. Detection of ATI during therapeutic drug monitoring postinduction but also periodically during maintenance therapy identifies individuals who may benefit from IFX dose escalation and/or the addition of an immunomodulator, as these interventions may reduce or eliminate ATI.

Humoral immune response and safety of SARS-CoV-2 vaccination in very early onset inflammatory bowel disease.

Children with very early onset inflammatory bowel disease (VEO-IBD) may respond differently to coronavirus disease 2019 (COVID-19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO-IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO-IBD experience robust humoral immune response to COVID-19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO-IBD respond well and safely to SARS-CoV-2 vaccination.

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Helicobacter pylori Antimicrobial Resistance Using Next-Generation Sequencing in Stool Samples in a Pediatric Population.

Helicobacter pylori ( H pylori ) eradication rates have declined globally, stressing the importance of antimicrobial susceptibility testing to inform treatment. Molecular tests such as next-generation sequencing (NGS) provide susceptibility data for the antibiotics used in the treatment of H pylori in a noninvasive, effective, and rapid manner. We obtained stool susceptibility testing using a novel NGS-based analysis and compared results with the current "gold standard" of gastric biopsy culture via agar dilution in 20 pediatric patients with evidence of H pylori in gastric biopsies. Stool NGS-based antimicrobial susceptibility analysis was highly concordant with agar dilution for no resistance (100% agreement), as well as clarithromycin, levofloxacin, and amoxicillin resistance (100%, 67%, and 100% agreement, respectively) but not concordant for metronidazole in our cohort of patients. Future studies involving a larger number of patients and geographical regions are needed to further validate this analysis.

Efficacy and Safety of Sulfasalazine Suspension in Children With Ulcerative Colitis.

BACKGROUND: Sulfasalazine (SZ) is commonly used to treat pediatric ulcerative colitis (UC). SZ can be compounded into a suspension form which is beneficial for children with difficulty swallowing a pill. Despite being utilized for over 40 years, there is a lack of published data on the efficacy and safety of SZ suspension in children with UC. Recently, third-party payors have begun refusing to pay for SZ suspension due to lack of data. METHODS: In this retrospective study, we reviewed the electronic medical records of patients ages <18 years diagnosed with UC from June 1999 to December 2019 at Boston Children's Hospital and treated with SZ suspension as a first-line agent. We obtained demographics, clinical, and endoscopic data to measure outcomes at 1 year and long term. RESULTS: Of 57 patients treated with SZ suspension, 52 (91%) had a follow-up and 26 of 52 (50%) remained in steroid-free remission at 1 year. Two patients were switched to SZ tablets due to nonmedical reasons and 11 (21%) required rescue treatment (2 infliximab, 1 tacrolimus, 8 6-mercaptopurine/azathioprine) within a year. Three required colectomy within a year and 5 in long term. Four (8%) developed nonserious adverse reactions and switched to 5-aminosalicylates (5-ASA) by 1 year. The median duration of long-term follow-up was 36 months (range, 2-205 months) with 28 requiring treatment escalation in long term. CONCLUSIONS: SZ suspension is a safe and effective treatment for UC in children with difficulty swallowing a pill. The 1-year remission rate on this treatment is comparable to 5-ASA utilized in children.

Efficacy and Safety of Tacrolimus or Infliximab Therapy in Children and Young Adults With Acute Severe Colitis.

INTRODUCTION: One-third of children and young adults admitted for management of acute severe colitis (ASC) fail intravenous corticosteroids. Infliximab (IFX) or tacrolimus (TAC) is often used to prevent urgent colectomy in these patients. However, no prior studies have reviewed the outcome of pediatric patients with ASC who were treated with either IFX or TAC. METHODS: We retrospectively identified 170 pediatric patients with ASC admitted to our institution who did not respond to intravenous corticosteroids and were subsequently treated with either IFX or TAC. We compared 6-month colectomy rates, time to colectomy, improvement in disease activity indices, and adverse effects. RESULTS: The mean age of patients in the IFX (n = 84) and TAC (n = 86) groups were 14 and 13.8 years, respectively. The median study follow-up time was 23 months. The rate of colectomy 6 months from rescue therapy was similar whether patients received IFX or TAC (22.6% vs 26.7%, respectively, P = 0.53). The mean decline in Pediatric Ulcerative Colitis Activity Index scores from admission to discharge in those treated with IFX (31.9) or TAC (29.8) was similar (P = 0.63). Three patients treated with IFX experienced infusion reactions. Six patients treated with TAC experienced changes in renal function or electrolytes, and 4 patients reported neurologic symptoms. CONCLUSIONS: There were no significant differences in the likelihood of colectomy 6 months after initiating IFX or TAC rescue therapy. Efficacy of both agents was comparable. The types of adverse effects differed by therapy. These data support the use of either TAC or IFX in children with ASC refractory to intravenous corticosteroids.

Factors Affecting Initial Humoral Immune Response to SARS-CoV-2 Vaccines Among Patients With Inflammatory Bowel Diseases.

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.

Denials, Dilly-dallying, and Despair: Navigating the Insurance Labyrinth to Obtain Medically Necessary Medications for Pediatric Inflammatory Bowel Disease Patients.

Increasingly, in the United States, the prescribing of high-cost drugs has become a challenge for physicians and other practitioners. Such drugs are highly regulated by third-party payers (aka insurance), as well as pharmacy benefit managers. Not infrequently, a clinician prescribing a medication will have the payment for the prescription denied by the third-party payer, with the end result being a delay in getting a medically necessary medication to a patient. This article highlights the challenges involved in the prior authorization and denial process, with a focus on pediatric inflammatory bowel disease. The article reviews the role of pharmacy benefits managers in restricting access to drugs, and the reasons why denials of medically necessary medications may occur. The article also provides information on how to appeal denials, how to write a letters of medical necessity, and how to conduct a proper peer-to-peer review. Advocacy from patients and clinicians will be important, as we want to reform the process in the future.

Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease.

BACKGROUND & AIMS: Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn's disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution. METHODS: We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups. RESULTS: Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naïve B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. Peripheral blood mononuclear cells from patients with active CD differed from those of active UC in that the peripheral blood mononuclear cells from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above. CONCLUSIONS: We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.

Agreement on Symptoms Between Children With Ulcerative Colitis and Their Caregivers: Towards Developing the TUMMY-UC.

ABSTRACT: As part of the development of the TUMMY-UC, a patient-reported outcome (PRO) measure for pediatric ulcerative colitis (UC), we aimed to explore agreement on UC symptoms between children and their caregivers. We conducted 44 interviews with children ages 8-12 years, who completed the PRO version of the TUMMY-UC, and their caregivers, who completed the observer-reported outcome (obsRO) version. There was excellent agreement between the total TUMMY-UC PRO and obsRO scores (intra-class correlation coefficient = 0.92 [95% confidence interval 0.74-0.98]). The obsRO scores were always within the same disease-activity category as the corresponding PRO score (ie, remission, mild and moderate-severe disease). There was a strong correlation of the TUMMY-UC PRO and obsRO scores with physician global assessment of disease activity (r = 0.94 and r = 0.90, respectively, P < 0.001) and the pediatric UC activity index (r = 0.95 and r = 0.96; P < 0.001). These data support conceptual equivalence between the PRO and obsRO TUMMY-UC versions, and provide support for their incorporation into one score.

Designing clinical trials in paediatric inflammatory bowel diseases: a PIBDnet commentary.

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children. METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text. RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text. CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.

Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn's disease : a randomised controlled trial.

OBJECTIVE: Crohn's disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD. DESIGN: This blinded randomised controlled trial allocated children 5-18 years with 1012.5 or remission using intention to treat analysis. RESULTS: 73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectin declined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycin led to remission in 10/12 (83%). CONCLUSIONS: The combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin. TRIAL REGISTRATION NUMBER: NCT01596894.

Curved planar reformatting and convolutional neural network-based segmentation of the small bowel for visualization and quantitative assessment of pediatric Crohn's disease from MRI.

BACKGROUND: Contrast-enhanced MRI of the small bowel is an effective imaging sequence for the detection and characterization of disease burden in pediatric Crohn's disease (CD). However, visualization and quantification of disease burden requires scrolling back and forth through 3D images to follow the anatomy of the bowel, and it can be difficult to fully appreciate the extent of disease. PURPOSE: To develop and evaluate a method that offers better visualization and quantitative assessment of CD from MRI. STUDY TYPE: Retrospective. POPULATION: Twenty-three pediatric patients with CD. FIELD STRENGTH/SEQUENCE: 1.5T MRI system and T1 -weighted postcontrast VIBE sequence. ASSESSMENT: The convolutional neural network (CNN) segmentation of the bowel's lumen, wall, and background was compared with manual boundary delineation. We assessed the reproducibility and the capability of the extracted markers to differentiate between different levels of disease defined after a consensus review by two experienced radiologists. STATISTICAL TESTS: The segmentation algorithm was assessed using the Dice similarity coefficient (DSC) and boundary distances between the CNN and manual boundary delineations. The capability of the extracted markers to differentiate between different disease levels was determined using a t-test. The reproducibility of the extracted markers was assessed using the mean relative difference (MRD), Pearson correlation, and Bland-Altman analysis. RESULTS: Our CNN exhibited DSCs of 75 ± 18%, 81 ± 8%, and 97 ± 2% for the lumen, wall, and background, respectively. The extracted markers of wall thickness at the location of min radius (P = 0.0013) and the median value of relative contrast enhancement (P = 0.0033) could differentiate active and nonactive disease segments. Other extracted markers could differentiate between segments with strictures and segments without strictures (P < 0.05). The observers' agreement in measuring stricture length was >3 times superior when computed on curved planar reformatting images compared with the conventional scheme. DATA CONCLUSION: The results of this study show that the newly developed method is efficient for visualization and assessment of CD. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1565-1576.

Microscopic/"Backwash" Ileitis and Its Association With Colonic Disease in New Onset Pediatric Ulcerative Colitis.

BACKGROUND: Microscopic ileitis and its association with pancolitis in adults with ulcerative colitis (UC) have been described. The incidence of ileitis and associations with colonic disease in pediatric UC have, however, not been thoroughly investigated. This study was undertaken to examine the prevalence of microscopic ileal inflammation at the time of initial diagnosis in a cohort of children with UC. METHODS: We reviewed colonoscopy and biopsy data at time of diagnosis from 105 children and young adults with treatment naïve UC; ileal and colonic mucosal biopsies were available on all patients. Ileal mucosal biopsies were examined for the presence and severity of ileal inflammation, and other histologic features. Concurrently obtained colonic mucosal biopsies were assessed to define the severity, distribution, and extent of disease; endoscopic and clinical follow-up data were reviewed. RESULTS: A total of 107 ileal mucosal biopsies and 693 corresponding colonic mucosal biopsies were examined. Seventeen of 105 patients (16%) were found to have ileal inflammation (mean age = 10.4 years, 59% girls), 14 (82%) of whom had histologic pancolitis. The presence of ileal inflammation was significantly associated with endoscopic pancolitis (P = 0.02). The association between histologic pancolitis, severity of active inflammation in the cecum, and ascending colon suggested a possible association with ileal inflammation (P = 0.06, 0.07, and 0.08 respectively), but did not reach statistical significance. CONCLUSION: Patients with new onset UC may have microscopic ileal inflammation at time of diagnosis, even if the terminal ileum appears macroscopically normal. The presence of endoscopic pancolitis is associated with the presence of histologic ileitis. In contrast to existing studies in adults, an association between the presence of ileitis and the histologic severity or the histologic extent of colitis was not observed. Children with microscopic ileitis in the context of UC do not need to be reclassified as "indeterminate colitis" or Crohn disease.