Physician workload and practice management in pediatric gastroenterology.

OBJECTIVES: The pediatric gastroenterology workforce has grown in the last few decades. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force to understand current pediatric gastroenterology organizations' practice structures. METHODS: 19-item electronic survey was distributed to NASPGHAN members who were clinical or academic division directors. RESULTS: 30% responded to the survey, all directors of academic practices. The median number of clinical sessions per week was seven sessions, and the median individual work relative value unit (wRVU) target for practices was 4000-4500. Healthcare team ratios compared to provider clinical full-time equivalent were reported as the following: Nursing 0.80, medical assistant 0.29, dietitian 0.29, social worker 0.14, and psychologist 0.13. Regarding compensation, 68.0% were salaried with bonus based on billing or director decision, 28.0% were salaried with no incentive pay, and 4.0% were salaried with a portion at risk if the target was not met, and a bonus was given if the target was met. Most practices participated in a wellness activity with the most common strategies being didactic lectures about physician burnout (80%), annual burnout check-ins (68%), and/or after-hours social activities (60%). CONCLUSIONS: Pediatric gastroenterology practices vary regarding clinical sessions per week and annual wRVU targets with the median at seven sessions per week and an annual goal of 4000-4500 wRVUs, similar to reported national benchmark goals at the 50th percentile. Healthcare teams, including nursing, medical assistants, dietitians, social workers, and psychologists, had similar ratios of staff to providers for all sizes and types of practices. Most practices are engaging in wellness initiatives.

Child Health Needs and the Pediatric Gastroenterology Workforce: 2020-2040.

This article is part of an American Board of Pediatrics Foundation-sponsored effort to analyze and forecast the pediatric subspecialty workforce between 2020 and 2040. Herein, an overview of the current pediatric gastroenterology workforce is provided, including demographics, work characteristics, and geographic distribution of practitioners. Brief context is provided on the changing nature of current practice models and the increasing prevalence of some commonly seen disorders. On the basis of a rigorous microsimulation workforce projection model, projected changes from 2020 to 2040 in the number of pediatric gastroenterologists and clinical workforce equivalents in the United States are presented. The article closes with a brief discussion of training, clinical practice, policy, and future workforce research implications of the data presented. This data-driven analysis suggests that the field of pediatric gastroenterology will continue to grow in scope and complexity, propelled by scientific advances and the increasing prevalence of many disorders relevant to the discipline. The workforce is projected to double by 2040, a growth rate faster than most other pediatric subspecialties. Disparities in care related to geography, race, and ethnicity are among the most significant challenges for the years ahead. Changes to training and education, incentives to meet the needs of underserved populations, and new multidisciplinary models for health care delivery will be necessary to optimally meet the volume, diversity, and complexity of children with gastroenterological diseases in the years ahead.

The Use of the Perioperative Nutrition Score in Postoperative Pediatric Inflammatory Bowel Disease Patients.

BACKGROUND AND OBJECTIVES: Preoperative malnutrition is associated with increased postoperative morbidity. The perioperative nutrition score (PONS) was developed to identify patients at risk of malnutrition. We sought to assess the correlation between preoperative PONS and postoperative outcomes in pediatric inflammatory bowel disease (IBD) patients. METHODS: We performed a retrospective cohort study of IBD patients, less than 21 years of age, who underwent elective bowel resection between June 2018 and November 2021. Patients were divided based upon whether they met PONS criteria. The primary outcome was postoperative surgical site infections. RESULTS: 96 patients were included. Sixty-one patients (64%) met at least one PONS criteria, while 35 patients (36%) met none. PONS positive patients more frequently received preoperative TPN supplementation (p < .001). There was no difference in preoperative oral nutritional supplementation between groups. Patients that screened positive for PONS had a longer hospital stay (p = .002), more readmissions (p = .029), and more surgical site infections (p = .002). CONCLUSIONS: Our data highlight the prevalence of malnutrition in the pediatric IBD population. Patients who screened positive had worse postoperative outcomes. Further, very few of these patients received preoperative optimization with oral nutritional supplementation. There is a need for standardization of nutritional evaluation to improve preoperative nutritional status and postoperative outcomes. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Retrospective Cohort.

Single-Center Retrospective Review of the Presentation and Initial Care of Esophageal Button Battery Impactions 2007-2020.

OBJECTIVE: The aims of this study were to characterize the patient population and initial presentation and care of esophageal button battery ingestion and provide descriptive data including factors affecting accurate diagnosis, duration of battery exposure, and battery removal. METHODS: This was a retrospective cohort study from 2007 to 2020 at a single-center, large-volume, urban academic pediatric hospital system. Included participants were children 6 months to 18 years old who underwent removal of an esophageal button battery impaction at our institution. RESULTS: Our cohort comprised 63 patients; ages ranged from 7 to 87 months with a median of 27 months. Median button battery size was 2.12 cm with 59% lodged in the proximal esophagus. A prolonged impaction, greater than 12 hours, occurred in 46% of patients. Risk ratio analysis demonstrated that lack of caregiver suspicion of ingestion was associated with prolonged impaction (risk ratio, 3.39; confidence interval, 2.15-5.34). Misdiagnosis of button battery ingestion occurred in 10% of cases. The majority of patients, 87%, required transfer from a referring facility with a median total distance of 37 miles (range, 1.4-160 miles) from home to facility where battery was removed. CONCLUSION AND RELEVANCE: This study describes the initial presentation and care of a large cohort of pediatric esophageal button battery ingestion. It emphasizes the continued need for primary prevention, prompt identification, and removal of these batteries. There are many challenges in caring for these patients involving multiple pediatric disciplines, and guidelines encompassing a multidisciplinary approach would be beneficial.

Physician Burnout in Pediatric Gastroenterology.

OBJECTIVES: Physicians are prone to burnout which can negatively affect the quality of patient care and lead to medical errors. Burnout can also affect physicians by impacting their personal relationships, their sense of career fulfillment, and job satisfaction. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a taskforce to investigate burnout among pediatric gastroenterologists. METHODS: A 35-item electronic survey was developed to collect demographic and practice information and characterize the well-being of pediatric gastroenterologists. Burnout was assessed employing 2 single-item measures adapted from the Maslach Burnout Inventory. The survey was distributed to NASPGHAN members 3 times from February 2020 to March 2020. Descriptive statistics, Chi-square, and Fisher exact tests were used. RESULTS: One thousand seven hundred ninety-one e-mails were successfully sent and 408 participants (22.7%) returned surveys. A total of 28.8% reported high risk for emotional exhaustion, 17.5% reported high risk for depersonalization, and 33% reported overall burnout. Participants 44 years of age or younger reported significantly more burnout than those 45 years and older ( P = 0.018). Contributors to high burnout identified included increased patient load/demands, insufficient nursing support, electronic health record (EHR) use, insufficient administrative staff, excessive on-call coverage, and more complex patients. Forty-four percent reported not having enough time for their personal life including family. A total of 16.2% of participants reported that they would not choose to be a pediatric gastroenterologist again. CONCLUSIONS: Pediatric gastroenterologists are at risk for emotional exhaustion, depersonalization, and overall burnout. Strategies to prevent physician burnout should be implemented as soon as feasibly possible to improve individual mental health and patient care.

Evolving Clinical Care in Esophageal Button Batteries: Impact of Expert-Opinion Guideline Adoption and Continued Gaps in Care.

BACKGROUND/OBJECTIVES: Esophageal button battery impactions (BBI) in children pose a significant danger to children. Although there are expert-opinion guidelines to help manage this population, few studies detail the impact of guidelines on the clinical care of these patients. With this study, we aimed to describe the care of these patients before and following adoption of guidelines at a single center. METHODS: Retrospective cohort study of patients with esophageal BBI at a single center, large volume, urban academic pediatric hospital system before adoption of expert-opinion guidelines (2007-2017) and following adoption (2018-2020). RESULTS: Cohort was comprised of 31 patients before adoption and 32 patients following adoption of guidelines. Patient characteristics did not differ between groups. After 2018, significantly more patients received acetic acid irrigation, initial cross-sectional imaging, and serial cross-sectional imaging. There was also an increase in intensive care unit (ICU) stays, number of intubations, nil per os time, and hospital length of stay. There was no difference in patient outcomes. CONCLUSION: This study describes a large cohort of pediatric esophageal BBI before and following adoption of guidelines. Findings detail increased adherence to guidelines resulting in more cross-sectional imaging which led to ICU stays, longer length of stays, and more nil per os time. This study emphasizes the need for multi-disciplinary guidelines as well as further multi-institutional study.

Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis.

INTRODUCTION: While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS-free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes. RESULTS: The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS-free remission, needed anti-tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS-free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87-0.96) were associated with outcomes, with the latter having a stronger association with CS-free remission. Patients with a >75% decrease by 12 weeks, had a 3-fold increased likelihood of CS-free remission at 1 year. DISCUSSION: Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.

Fellow Entrustment for the Common Pediatric Subspecialty Entrustable Professional Activities Across Subspecialties.

OBJECTIVE: To determine the relationship between level of supervision (LOS) ratings for the Common Pediatric Subspecialty Entrustable Professional Activities (EPAs) with their associated subcompetency milestones across subspecialties and by fellowship training year. METHODS: Clinical Competency Committees (CCCs) in 14 pediatric subspecialties submitted LOS ratings for 6 Common Subspecialty EPAs and subcompetency milestone levels mapped to these EPAs. We examined associations between these subcompetency milestone levels and LOS ratings across subspecialty training year by fitting per-EPA linear mixed effects models, regressing LOS rating on milestone level and on training year. RESULTS: CCCs from 211 pediatric fellowship programs provided data for 369 first, 336 second, and 331 third year fellows. Mean subcompetency milestone levels increased similarly among subspecialties for most EPAs compared with the reference, Adolescent Medicine. Mean subcompetency milestones mapped to each EPA and mean EPA LOS ratings generally increased by training year across all subspecialties. CONCLUSIONS: Subcompetency milestones levels mapped to each Common Subspecialty EPA and the EPA LOS ratings increase similarly across subspecialties and by training year, providing validity evidence for using EPA LOS to assess pediatric subspecialty trainee performance. This study supports the development of tools to facilitated the CCC evaluation process across all pediatric subspecialties.

Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression.

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.

Creation of a Pediatric Choledocholithiasis Prediction Model.

BACKGROUND: Definitive non-invasive detection of pediatric choledocholithiasis could allow more efficient identification of those patients who are most likely to benefit from therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for stone extraction. OBJECTIVE: To craft a pediatric choledocholithiasis prediction model using a combination of commonly available serum laboratory values and ultrasound results. METHODS: A retrospective review of laboratory and imaging results from 316 pediatric patients who underwent intraoperative cholangiogram or ERCP due to suspicion of choledocholithiasis were collected and compared to presence of common bile duct stones on cholangiography. Multivariate logistic regression with supervised machine learning was used to create a predictive scoring model. Monte-Carlo cross-validation was used to validate the scoring model and a score threshold that would provide at least 90% specificity for choledocholithiasis was determined in an effort to minimize non-therapeutic ERCP. RESULTS: Alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, and common bile duct diameter via ultrasound were found to be the key clinical variables to determine the likelihood of choledocholithiasis. The dictated specificity threshold of 90.3% yielded a sensitivity of 40.8% and overall accuracy of 71.5% in detecting choledocholithiasis. Positive predictive value was 71.4% and negative predictive value was 72.1%. CONCLUSION: Our novel pediatric choledocholithiasis predictive model is a highly specific tool to suggest ERCP in the setting of likely choledocholithiasis.

Site- and Taxa-Specific Disease-Associated Oral Microbial Structures Distinguish Inflammatory Bowel Diseases.

BACKGROUND: The gut and oral microbiome have independently been shown to be associated with inflammatory bowel disease (IBD). However, it is not known to what extent gut and oral microbial disease markers converge in terms of their composition in IBD. Further, the spatial and temporal variation within the oral microenvironments of IBD remain to be elucidated. PATIENTS AND METHODS: We used a prospectively recruited cohort of patients with IBD (n = 47) and unrelated healthy control patients (n = 18) to examine the spatial and temporal distribution of microbiota within the various oral microenvironments, represented by saliva, tongue, buccal mucosa, and plaque, and compared them with stool. Microbiome characterization was performed using 16S rRNA gene sequencing. RESULTS: The oral microbiome displayed IBD-associated dysbiosis, in a site- and taxa-specific manner. Plaque samples depicted a relatively severe degree of dysbiosis, and the disease-associated dysbiotic bacterial groups were predominantly the members of the phylum Firmicutes. Our 16S rRNA gene analyses show that oral microbiota can distinguish patients with IBD from healthy control patients, with salivary microbiota performing the best, closely matched by stool and other oral sites. Longitudinal profiles of microbial composition suggest that some taxa are more consistently perturbed than others, preferentially in a site-dependent fashion. CONCLUSIONS: Collectively, these data indicate the potential of using oral microbial profiles in screening and monitoring patients with IBD. Furthermore, these results support the importance of spatial and longitudinal microbiome sampling to interpret disease-associated dysbiotic states and eventually to gain insights into disease pathogenesis.

Serial MRI Findings After Endoscopic Removal of Button Battery From the Esophagus.

OBJECTIVE. The purpose of this study was to evaluate findings at serial MRI after endoscopic removal of a button battery from the esophagus in a series of pediatric patients. MATERIALS AND METHODS. Serial MRI examinations after removal of a button battery from the esophagus were reviewed retrospectively for the presence of mediastinal edema; imaging characteristics of the aorta and arteries; imaging characteristics of the trachea; and imaging characteristics of the esophageal wall at the level of injury. RESULTS. A total of 48 MRI examinations were performed on 19 patients, 89% (17/19) in the first 48 hours after battery removal. Serial MRI was performed for 84% (16/19) of patients. Initial MRI showed extensive mediastinal edema in all 17 patients who underwent MRI in the first 48 hours. Edema directly abutted major arteries in all 17 patients and abutted the airway in all 10 patients with proximal esophageal injury. Arterial vascular changes were seen in 30% (3/10) of patients with proximal esophageal injury and 57% (4/7) of patients with mid or distalesophageal injury. Airway changes were seen in 80% (8/10) of patients with proximal esophageal injury. Serial MRI showed improvement of airway changes in all patients and improvement in vessel wall changes in all but one (25%, 1/4) of the patients who had mid or distal esophageal injury. Four patients (21% [4/19]) had contained esophageal leak on esophagrams. No patients in our series developed a tracheoesophageal or vascular-enteric fistula. CONCLUSION. Our case series provides important information on natural history of MRI findings in children after endoscopic removal of a button battery from the esophagus. Further studies are needed to determine the imaging findings most sensitive and specific for severe complications, such as tracheoesophageal fistula and vascular-enteric fistula.

Agreement of Program Directors With Clinical Competency Committees for Fellow Entrustment.

OBJECTIVES: Fellowship program directors (FPD) and Clinical Competency Committees (CCCs) both assess fellow performance. We examined the association of entrustment levels determined by the FPD with those of the CCC for 6 common pediatric subspecialty entrustable professional activities (EPAs), hypothesizing there would be strong correlation and minimal bias between these raters. METHODS: The FPDs and CCCs separately assigned a level of supervision to each of their fellows for 6 common pediatric subspecialty EPAs. For each EPA, we determined the correlation between FPD and CCC assessments and calculated bias as CCC minus FPD values for when the FPD was or was not a member of the CCC. In addition, we examined the effect of program size, FPD understanding of EPAs, and subspecialty on the correlations. Data were obtained in fall 2014 and spring 2015. RESULTS: A total of 1040 fellows were assessed in the fall and 1048 in the spring. In both periods and for each EPA, there was a strong correlation between FPD and CCC supervision levels (P < .001). The correlation was somewhat lower when the FPD was not a CCC member (P < .001). Overall bias in both periods was small. CONCLUSIONS: The correlation between FPD and CCC assignment of EPA supervision levels is strong. Although slightly weaker when the FPD is not a CCC member, bias is small, so this is likely unimportant in determining fellow entrustment level. The similar performance ratings of FPDs and CCCs support the validity argument for EPAs as competency-based assessment tools.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on Entrustable Professional Activities: Development of Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities.

Quality training in pediatric gastroenterology, hepatology, and nutrition is essential for the future of our specialty from advancing the science through research to providing clinical care for children with gastrointestinal, hepatic and nutritional disorders. As educational theory has developed, both the American Board of Pediatrics (ABP) and the Accreditation Council for Graduate Medical Education (ACGME) have commissioned projects to better define training including core competencies, and milestones with the goal of competency-based assessment. Seeking to provide a clinical context for these competencies and milestones, the ABP commissioned a project for each pediatric subspecialty to develop entrustable professional activities (EPA) while at the same time developing EPAs that are common to all pediatric subspecialties. North American Society for Pediatric Gastroenterology, Hepatology, Nutrition (NASPGHAN) commissioned an EPA Task Force to develop the pediatric gastroenterology, hepatology and nutrition EPAs. This document serves as an introduction to EPAs, including their historical background, underlying educational theory, and the process used to develop the pediatric gastroenterology, hepatology and nutrition EPAs in the United States of America.

Management of Anti-drug Antibodies to Biologic Medications in Children With Inflammatory Bowel Disease.

BACKGROUND: Treatment of pediatric inflammatory bowel disease (IBD) with monoclonal anti- tumor necrosis factor-alpha (TNFα) can result in immunogenicity and formation of anti-drug antibodies (ADAs). ADAs are associated with loss of clinical response and worsening disease progression. Data examining treatment interventions to overcome ADA in pediatric patients with IBD are lacking. RESULTS: Medical records were reviewed from 234 children and adolescents with IBD treated with infliximab or adalimumab who underwent therapeutic drug monitoring (626 tests). All patients who had detectable antibodies were further analyzed. A total 58 patients (24.8%) developed ADA while being treated with infliximab or adalimumab. The incidence of antibody development was 12.9 per 100 person-years of anti-TNF treatment. Twenty-eight patients underwent dose optimization and 54% had undetectable ADA on follow-up monitoring. The mean duration of antibody suppression was 16.8 ±â€Š10.9 months in those who were successfully suppressed with optimization. Patients who switched to a second anti-TNF medication were not more likely to develop antibodies to the second agent. CONCLUSIONS: With limited therapies for IBD and the chronicity of the disease, we advocate salvage of the current anti-TNF through dose optimization in pediatric patients with antibody level <10 U/mL.

Performance of Interferon-Gamma Release Assays for Tuberculosis Screening in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to analyze the diagnostic accuracy and utility of QuantiFERON-TB Gold In-Tube, an interferon-gamma release assay (IGRA), as a screening tool for latent tuberculosis infection (LTBI) in pediatric patients with inflammatory bowel disease (IBD) undergoing treatment with anti-tumor necrosis factor (anti-TNF) medications. To describe cases of tuberculosis in the pediatric IBD population, TB treatment courses, outcomes, and their effect on IBD management. METHODS: A single-center, retrospective cohort study of pediatric IBD patients who underwent tuberculosis screening. IGRA testing from 2011 to 2017 were analyzed to determine result rates, characteristics, and outcomes. RESULTS: One thousand seven hundred fifty-four (1,754) tests were performed on 859 patients. One thousand six hundred thirty-four (1,634) tests were negative, 9 were positive, and 111 were indeterminate. Eight of 9 positive tests resulted during repeat annual screening while receiving IBD treatment. Five patients were treated for latent tuberculosis infection (LTBI), and 4 were false-positives. IBD therapy was interrupted in 3 patients, with no negative long-term outcomes. We report 1 known false-negative, in a patient who developed disseminated TB on anti-TNF therapy. Indeterminate testing rates were higher at IBD diagnosis than during treatment (10.3% vs 5.3%, P < 0.001). Follow-up testing of indeterminate results was negative in all patients retested, with 14 patients lost to follow-up. No patient with indeterminate testing developed TB. CONCLUSIONS: IGRAs are a useful tool to screen for LTBI, both before anti-TNF therapy and during treatment. Results should be used in concert with detailed history and examination. Positive and indeterminate results should be promptly repeated for timely TB diagnosis and to minimize interruptions in IBD therapy.

Characterization of Stool Virome in Children Newly Diagnosed With Moderate to Severe Ulcerative Colitis.

BACKGROUND: Viral infections have been suggested as possible triggers for the onset of ulcerative colitis (UC). METHODS: We employed VirCapSeq-Vert, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe UC. We surveyed fecal samples collected at presentation, after symptom remission, and from a control group diagnosed with irritable bowel syndrome. RESULTS: Seventy subjects with UC (mean age 13 years, 45 had moderate symptoms, 25 had severe, 69 of 70 had a Mayo endoscopy subscore 2/3) were studied. We detected a wide range of animal viruses that were taxonomically classified into 12 viral families. A virus was present in 50% of fecal samples collected at presentation, 41% of samples collected after remission, and 40% of samples in our control group. The most frequently identified viruses were diet-based gyroviruses. The UC cohort had a significantly higher prevalence of anelloviruses compared with the control cohort. However, we did not identify a single virus that can be implicated in the onset of UC and did not find an association between UC disease severity and viral presence. CONCLUSION: Presence of virus in stool was not associated with the onset of pediatric UC.

Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study.

BACKGROUND: Lack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course. METHODS: In this inception cohort study, we recruited paediatric patients aged 4-17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada. Patients initially received standardised mesalazine or corticosteroids, with pre-established criteria for escalation to immunomodulators (ie, thiopurines) or anti-tumor necrosis factor-α (TNFα) therapy. We used RNA sequencing to define rectal gene expression before treatment, and 16S sequencing to characterise rectal and faecal microbiota. The primary outcome was week 52 corticosteroid-free remission with no therapy beyond mesalazine. We assessed factors associated with the primary outcome using logistic regression models of the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01536535. FINDINGS: Between July 10, 2012, and April 21, 2015, of 467 patients recruited, 428 started medical therapy, of whom 400 (93%) were evaluable at 52 weeks and 386 (90%) completed the study period with no protocol violations. 150 (38%) of 400 participants achieved week 52 corticosteroid-free remission, of whom 147 (98%) were taking mesalazine and three (2%) were taking no medication. 74 (19%) of 400 were escalated to immunomodulators alone, 123 (31%) anti-TNFα therapy, and 25 (6%) colectomy. Low baseline clinical severity, high baseline haemoglobin, and week 4 clinical remission were associated with achieving week 52 corticosteroid-free remission (n=386, logistic model area under the curve [AUC] 0·70, 95% CI 0·65-0·75; specificity 77%, 95% CI 71-82). Baseline severity and remission by week 4 were validated in an independent cohort of 274 paediatric patients with newly diagnosed ulcerative colitis. After adjusting for clinical predictors, an antimicrobial peptide gene signature (odds ratio [OR] 0·57, 95% CI 0·39-0·81; p=0·002) and abundance of Ruminococcaceae (OR 1·43, 1·02-2·00; p=0·04), and Sutterella (OR 0·81, 0·65-1·00; p=0·05) were independently associated with week 52 corticosteroid-free remission. INTERPRETATION: Our findings support the utility of initial clinical activity and treatment response by 4 weeks to predict week 52 corticosteroid-free remission with mesalazine alone in children who are newly diagnosed with ulcerative colitis. The development of personalised clinical and biological signatures holds the promise of informing ulcerative colitis therapeutic decisions. FUNDING: US National Institutes of Health.