OBJECTIVE:To assess the safety and efficacy of high-dose, oral cholecalciferol supplementation in children and young adults with inflammatory bowel disease treated with infliximab or vedolizumab. STUDY DESIGN:This was a prospective, longitudinal (1 year), open-label study of directly observed high-dose oral cholecalciferol administered every 4-8 weeks. Participants received either 100 000 IU every 4-6 weeks or 200 000 IU every 6-8 weeks, depending on the participant's infusion schedule. Dosing was titrated to a goal 25-hydroxyvitamin D (25-OHD) trough level of 40-60 ng/mL. Safety was assessed by spot urinary calcium and creatinine, and serum calcium levels. RESULTS:Participants' serum 25-OHD levels increased by a mean of 18.1 ng/mL (P < .001). At study conclusion, 58% (P < .001) and 91% (P < .001) of participants had 25-OHD levels greater than 40 ng/mL and 30 ng/mL, respectively. The response to cholecalciferol did not differ between patients with Crohn's disease or ulcerative colitis (P = .74). No adverse effects were observed, including changes in serum or urinary calcium levels. Mean spot urinary calcium to creatinine ratio 0.10 at baseline and 0.09 at study conclusion (P = .26). CONCLUSIONS:High-dose, intermittent cholecalciferol is a safe and effective approach to achieving and maintaining adequate 25-OHD in young patients with inflammatory bowel disease. TRIAL REGISTRATION:https://clinicaltrials.gov/study/NCT04331639.

OBJECTIVES:Sulfasalazine (SZ) and 5-aminosalicylates (5-ASA) have been widely used treatments for ulcerative colitis (UC). Although some studies suggest SZ may be superior, limited data exists comparing the two in children. This study aimed to describe real-world data on their comparative safety and efficacy in children and the impact of switching between SZ and 5-ASA before treatment escalation. METHODS:We retrospectively reviewed the electronic medical records of children diagnosed with UC between June 1999 and December 2019 at Boston Children's Hospital. We described outcomes at 1 year and long-term in patients treated with SZ or 5-ASA as a first-line maintenance agent. RESULTS:Among 433 patients (age 0-19 years), 124 started on SZ and 309 on 5-ASA. Forty-eight patients switched between the two drugs within the first year, and 74 switched during long-term follow-up. The main reason for switching from SZ to 5-ASA was adverse reactions. At 1 year, 54%, 44.3%, and 36.6% of patients on SZ, 5-ASA, and those who switched, respectively, were in steroid-free remission (p = 0.13). Patients who switched due to lack of efficacy or adverse reactions were four times more likely to escalate treatment compared to nonmedical reasons. Patients with Pediatric Ulcerative Colitis Activity Index >65 at the diagnosis are more likely to require treatment escalation (p = 0.0043). CONCLUSIONS:SZ and 5-ASA are effective first-line treatments for mild to moderate pediatric UC. SZ tends to have more minor adverse reactions. Switching between SZ and 5-ASA does not offer therapeutic benefits, and disease severity at diagnosis predicts early treatment escalation.

Small bowel into small bowel intussusception can present with symptoms similar to those observed in patients with more common small bowel into large bowel intussusception. In most cases, intussusceptions isolated to the small bowel are self-limited and less likely to result in bowel ischemia. Nonetheless, any patient with recurrent intussusception should be evaluated to assess location and for the presence of a pathologic lead point. We report a patient with recurrent small bowel into small bowel intussusception who underwent a comprehensive evaluation that revealed lymphoid hyperplasia in the absence of a pathologic lead point. His symptoms resolved after a dose of oral dexamethasone.

OBJECTIVES:Previous studies have demonstrated a relationship between socioeconomic disparities and missed clinic visits (MCV). However, the relationship between patient-preferred language and MCVs, particularly with respect to telemedicine, remains relatively underexplored. We sought to characterize the associations between MCV and patient-level predictors, including preferred language, in a large single-center pediatric gastroenterology, hepatology, and nutrition practice. METHODS:This retrospective longitudinal cohort study included all missed or completed outpatient visits in the Gastroenterology, Hepatology, and Nutrition Programs at Boston Children's Hospital from January 1, 2016 to May 20, 2022. Univariate and multivariate hierarchical generalized linear mixed models were employed to identify associations between visit- and patient-level predictors and an MCV outcome. RESULTS:A total of 300,201 visits from 70,710 patients residing in Massachusetts were included. Univariate analyses revealed higher MCV odds for Hispanic patients and those from areas with the highest Social Vulnerability Index (SVI), and these odds increased with telemedicine (Hispanic in-person odds ratio [OR] 5.21 [(95% confidence interval) 4.93-5.52] vs. telemedicine OR 8.79 [7.85-9.83]; highest SVI in-person OR 5.28 [4.95-5.64] vs. telemedicine OR 7.82 [6.84-8.96]). Controlled multivariate analyses revealed that among six language groups, only Spanish language preference was associated with higher MCV odds, which increased with telemedicine (Spanish in-person adjusted OR [aOR] 1.35 [1.24-1.48] vs. telemedicine aOR 2.1 [1.83-2.44]). CONCLUSIONS:Patients preferring Spanish experience unique barriers to care beyond those faced by other language preference groups, and telemedicine may exacerbate these barriers.

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.

BACKGROUND Screening for iron deficiency anemia (IDA) is important in managing pediatric patients with inflammatory bowel disease (IBD). Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous (IV) iron to treat IDA in this population. AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center. METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019. 92 patients met study criteria for IDA, of which 57 received IV iron, 17 received oral iron, and 18 were discharged prior to receiving iron therapy. RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9 (± 0.2) g/dL in mean (± SE) hemoglobin (Hb) concentration by the first ambulatory follow-up, compared to patients who received oral iron 0.8 (± 0.3) g/dL or no iron 0.8 (± 0.3) g/dL (P = 0.03). One out of 57 (1.8%) patients that received IV iron therapy experienced an adverse reaction. CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

To provide optimal, equitable care to patients, hospital systems must have intentional efforts to advance health equity. We present both intentional and actionable steps that our senior executive leadership prioritized to improve the health equity of the children and families we serve and to create a more inclusive working and learning environment for our employees, staff, faculty, and trainees in our academic pediatric medical center. The four key concepts or lessons learned that we found essential to successfully advancing and sustaining equity, diversity, and inclusion (EDI) in our academic pediatric medical center were to 1) Prioritize the strategy for EDI at the levels of the Board of Trustees and senior executive hospital leadership, 2) Collaborate with multi-disciplinary departments, offices, programs, and subject matter experts, 3) Take an Academic Approach by creating educational initiatives and scholarship in EDI, and 4) Commit to intentionality and accountability in the work by developing and tracking metrics for EDI and health equity safety disparities. Our hospital’s approach to its EDI goals and initiatives can serve as a roadmap for other academic medical centers and healthcare organizations in their efforts to improve health equity for all patients, families, and communities.

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.

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.

Objective: Vitamin D deficiency is prevalent in patients with inflammatory bowel disease (IBD). The goal of this study was to assess the efficacy and safety of high-dose, interval cholecalciferol administration in patients with IBD receiving infliximab. Methods: This prospective, longitudinal, open-label study enrolled pediatric and young adult patients with IBD and vitamin D deficiency. Subjects received 50,000 IU every 4 to 5 weeks (n = 11) or 100,000 IU every 6 to 8 weeks (n = 32) of oral cholecalciferol for 1 year. Dosing was directly observed and administered in conjunction with infliximab infusions. The primary endpoint was vitamin D sufficiency, defined as a 25-hydroxy-vitamin D (25-OHD) level >= 30 ng/mL. Results: Forty-three participants constituted the primary analysis population. 25-OHD levels reached steady-state after the third dose, and mean increases in 25-OHD levels were 8 vs. 4.5 ng/mL in the 100,000 IU vs. 50,000 IU treatment groups, respectively. Only 43.8% of patients receiving 100,000 IU and 18.2% of patients receiving 50,000 IU achieved sufficiency. There was no difference in the 25-OHD level responsiveness in patients with Crohn disease versus those with ulcerative colitis (P = 0.72). There was no correlation between 25-OHD levels and clinical disease activity in patients with Crohn disease (P = 0.85) or ulcerative colitis (P = 0.24). Conclusions: Supplementation with cholecalciferol was well-tolerated and direct observation is a promising paradigm for ensuring compliance with therapy. Patients with IBD, however, appear to require high doses of cholecalciferol, with less than half of patients (37% overall) achieving vitamin D sufficiency. Additional studies are necessary to determine the optimal treatment regimens.

The inflammatory bowel diseases, including ulcerative colitis and Crohn’s Disease, are chronic intestinal inflammatory disorders, likely resulting from a confluence of genetic vulnerabilities and environmental exposures. Existing therapies center on the use of broad-spectrum anti-inflammatory and immunosuppressive medications. Although newer classes of biologic therapies have introduced some mechanistic specificity, most patients and parents remain concerned about the potential effects of these agents when used in the long term. Existing data have implicated the intestinal microbiome in the pathogenesis of inflammatory bowel disease (1). Although our understanding is incomplete, it is apparent that certain bacteria or bacterial compositions can impose a dysbiosis that contributes to the development of an inflammatory intestinal milieu. The most effective long-term approach to impact the intestinal microbiome is sustained dietary interventions. Although isolated dietary restriction or supplementation has generally been ineffective, the application of the specific carbohydrate diet (SCD) can affect the constituents of the microbiome (2). Adherence to SCD can favorably impact clinical symptoms and quality of life in patients with inflammatory bowel disease (3). More recent studies have demonstrated endoscopic improvement in response to this diet approach (4). Suskind et al (5) report the obstacles associated with initiating and maintaining a specific carbohydrate diet (SCD). The authors interviewed parents of 10 patients who had either tried or opted not to try the inclusion of SCD in their child’s IBD management. Two patients opted not to try the SCD. One patient had concomitant dietary restrictions that would have made any further elimination untenable, and another patient had severe disease mandating a more expedient pharmacologic approach. Of those patients that initiated the SCD, four discontinued the diet. Three did so because of a lack of perceived effect. However, the study was not designed nor powered to comment on the clinical impact of SCD on patients. The fourth patient developed a Clostridium difficile infection requiring antibiotic therapy and opted not to restart the study. This article is important because it is among the first to systematically report the difficulties in pursuing this type of dietary intervention. They collected data from semistructured interviews and used an inductive coding regimen to develop thematic categories. Even among the relatively small sample size included in this study, it became clear that the biggest obstacles to pursuing a SCD included cost, time spent preparing special foods/meals, and the psychosocial impact of the diet on the patients’ quality of life. While the article did not include race or ethnicity data, the authors proposed several factors that have the potential to impact disproportionately less financially resourced and more geographically isolated populations. The less processed foods that are the mainstay of the SCD are typically more expensive per unit than highly processed foods. In addition, the availability and selection of less processed foods are limited in the smaller community markets and convenience stores found in urban centers. This means that patients living in urban centers, who likely have less secure transportation, must bear the added imputed cost of extra time and expenditure when challenged with adhering to the SCD. The authors propose some potential solutions to address identified barriers to adherence to SCD. FDA designated labeling, analogous to what is afforded to those adhering to gluten-free diets, would make it easier for parents shopping for SCD foods. Designations of this type would also facilitate the provision of SCD-restricted alternatives in school lunches. The ability to access Flexible Spending monies, which are already available to those shopping gluten free, would help offset the added cost of SCD compliant foods. However, these accounts are either unavailable to those working in entry-level, hourly, or per diem jobs or irrelevant to those living paycheck to paycheck. Studies of this type are critical as investigators and clinicians move forward to identify nonpharmacologic and more holistic approaches to managing chronic diseases, including IBD. Investigators, insurers, and legislators will have to consider the cost/benefit analysis, both in terms of dollars and quality of life that accompanies any recommendations concerning lifestyle and dietary recommendations. It is only by gaining a better understanding of the real or perceived obstacles imparted by these interventions that effective initiatives can be developed.

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

A two-and-one-half-year-old previously healthy female presented with a ten-week history of watery diarrhea, nonbilious and nonbloody emesis, and low-grade fevers. She was found to have severe hypoalbuminemia and hypogammaglobulinemia. Her symptoms persisted, and she became dependent on parenteral nutrition. Biopsies obtained during subsequent endoscopic and colonoscopic studies revealed findings consistent with collagenous gastroenterocolitis. She responded to an empiric course of prednisone, but her symptoms recurred shortly after transitioning to oral budesonide. After successful reinduction with intravenous prednisone, intramuscular methotrexate was initiated. She remained asymptomatic during a 15-month course of therapy, and she continued to do well clinically until approximately nine months after weaning off methotrexate. At that point, she experienced a recurrence of diarrhea, and repeat endoscopic evaluation confirmed collagenous colitis. This responded nicely to a short course of oral budesonide, and she has since remained asymptomatic and off any therapy.

The preoperative management of anesthesia in children differs from that employed in adults, including employing age-group appropriate language, understanding the dynamics of the child's family, and assessing the patient's developmental stage. Children are not small adults. Hence, we must have an understanding of the variability of each child's age and family-specific needs in an effort to develop a customized anesthesia management plan. The anesthesiologist must appreciate the stress the patients and their families may be experiencing. The anesthesiologist must review the child's presenting medical and psychological conditions. In this chapter, the clinical significance and potential strategies for enhancing pediatric healthcare outcomes will be discussed.

Protein-losing enteropathy (PLE) in the setting of severe iron deficiency anemia (IDA) and excessive cow milk intake is an uncommonly recognized phenomenon. Here, we describe a series of 7 toddlers who presented for evaluation of edema in the setting of excessive cow milk intake between November 2016 and January 2019. Laboratory studies in each patient were consistent with IDA and hypoalbuminemia with evidence of PLE. Diagnostic evaluation and treatment of each patient differed, although all were instructed to restrict cow milk and provided with oral iron supplementation. The edema had resolved, and the IDA had improved in all 7 patients by the time of their follow-up outpatient appointments. Iron deficiency and PLE should be considered in patients who present with anasarca.

ABSTRACTObjectives:The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis.Methods:A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10–12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left‐sided and proctosigmoiditis).Results:Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ± 20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut‐points with misclassification rates of approximately 30%.Conclusions:A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.

Purpose: We seek to determine how youth with chronic medical conditions experience alcohol screening and counseling. Methods: Adolescents with type I diabetes, juvenile idiopathic arthritis, moderate persistent asthma, cystic fibrosis, attention deficit hyperactivity disorder, or inflammatory bowel disease were surveyed. Descriptive statistics and regression analysis quantified rates of asking and counseling about alcohol. Results: Of 390 participants (75.1% white/non-Hispanic, 51.8% female, average age 16.4 years), 70% reported being asked about their alcohol use by a healthcare provider, and 76% reported receiving at least one message regarding alcohol and health. Of past year drinkers, 54% disclosed use to their provider. Only 2.0% of youth reported receiving the message "I should not drink." Conclusions: Most youth with chronic medical conditions were asked and counseled about alcohol use although few heard unambiguous recommendations to avoid alcohol consumption. (C) 2019 Society for Adolescent Health and Medicine. All rights reserved.

Background: BT-11 is an oral, gut-restricted, small molecule investigational new drug for Crohn's disease (CD) and ulcerative colitis (UC) that targets the Lanthionine Synthetase Clike 2 (LANCL2) pathway.Through the LANCL2 pathway, BT-11 modulates late-stage glycolysis in CD4+ T cells to bias cellular metabolism leading to increased regulatory function.BT-11 has displayed consistent downregulation of inflammation and upregulation of regulatory responses in 5 mouse models and one pig model of inflammatory bowel disease (IBD) as well as primary samples (PBMCs and LPMCs) from CD and UC patients.Methods: Oral BT-11 was assessed for safety and tolerability in normal healthy volunteers (n = 70) in a randomized, double-blind, placebo-controlled trial.Volunteers were randomized into five single ascending dose cohorts (7.7 ? 100 mg/kg, p.o.) and three multiple ascending dose cohorts (7.7 ? 100 mg/kg QD for seven days, p.o.).Safety and tolerability were assessed by adverse event (AE) reporting, vital signs, ECG, hematology and clinical chemistry.Fecal concentrations of BT-11 and calprotectin were measured.Results: Single and seven-day dosing with BT-11 does not result in increases in total AE or gastrointestinal AE rates in individual dose cohorts and overall pooled active group.No SAEs were observed over the course of the study.Oral BT-11 dosing does not result in any clinically significant findings by biochemistry, coagulation, ECG, hematology, or urinalysis.Single oral doses of BT-11 resulted in 18.3 and 19.5 μg/g mean differences in fecal calprotectin, respectively, 24 hours after dosing in 7.7 mg/kg (12.5 μg/g, n = 6) and 25 mg/kg (11.3 μg/g, n = 6) cohorts relative to placebo (30.8 μg/g, n = 10).Mean fecal concentrations of BT-11 in the 7.7 mg/kg cohort were observed to be 2.39 mg/g (n = 8) on day 7 after seven days of dosing.Fecal concentrations were observed to scale in a near dose-proportional level in 50 mg/kg (21.8 mg/g, n = 8) and 100 mg/kg (31.9 mg/g, n = 8) cohorts.Conclusions.BT-11 is safe and well-tolerated up to daily doses of 100 mg/kg (approximately 7 ?8 g total dose) in healthy volunteers.Phase II studies in CD and UC for BT-11 are on-going. Tu1755