Fatigue in pediatric inflammatory bowel diseases: A systematic review and a single center experience.

OBJECTIVES: We aimed to review the literature on fatigue in pediatric inflammatory bowel diseases (PIBD), to explore how it is measured, and approximate its rate in an inception pediatric cohort. METHODS: Studies on fatigue were systematically reviewed and selected by two authors. Next, we retrieved the two fatigue-related questions of the IMPACT-III questionnaire at 4 and 12 months after diagnosis from a prospectively maintained cohort of PIBD patients, each scoring 0-100 (lower scores imply more fatigue), and 44 healthy controls. RESULTS: The systematic review identified 14 studies reporting fatigue in children, of which nine had fatigue as the primary outcome and only two provided rates of fatigue. No standalone index was identified for measuring fatigue specifically for PIBD. Of 80 children included in the inception cohort, 62 (78%) scored an average of ≤75 on the two IMPACT-III questions (approximating at least mild fatigue), 26 (33%) scored ≤50 (at least moderate fatigue) and nine (11%) scored ≤25 (severe fatigue). In comparison, only four (9%) healthy children scored at least moderate fatigue (p = 0.007). Fatigue rates at 12 months were only slightly and nonsignificantly lower. Fatigue of any severity was reported in 92% children with active disease versus 63% of those in clinical remission (p = 0.01). CONCLUSION: Literature reporting on fatigue in PIBD is scarce, and no PIBD-specific tool is available to measure fatigue. In our cohort, fatigue-related questions were frequently scored low in children with IBD, mainly among children with active disease but also during clinical remission.

Residence in Peripheral Regions and Low Socioeconomic Status Are Associated With Worse Outcomes of Inflammatory Bowel Diseases: A Nationwide Study From the epi-IIRN.

BACKGROUND: Timely access to quality medical care impacts patient outcomes in inflammatory bowel disease (IBD). In a nationwide study from the epidemiology group of the Israeli IBD research nucleus we aimed to assess the impact of residence and socioeconomic status (SES) on disease outcomes. METHODS: We utilized data from the 4 health maintenance organizations in Israel, representing 98% of the population. Regions were defined as central, northern and southern; SES was graded from lowest to highest (from 1 to 4) as per Israel Central Bureau of Statistics. The primary outcome was steroid dependency, with secondary outcomes of surgeries and biologic therapy use. RESULTS: A total of 28 216 IBD patients were included: 15 818 (56%) Crohn's disease (CD) and 12 398 (44%) ulcerative colitis; 74%, 12% and 14% resided in central, southern, and northern Israel, respectively (SES 1: 21%, SES 4: 12%). Lower SES was associated with steroid dependency (20% in SES 1 vs 12% in SES 4 in CD; P < .001; and 18% vs 12% in ulcerative colitis; P < .001), and higher surgery rates (12% vs 7%; P < .001, and 1.4% vs 0.7%; P = .115, respectively). There were higher steroid dependency and CD surgery rates in peripheral vs central regions. In multivariable models, both SES and peripheral region were independently associated with poorer outcomes. CONCLUSIONS: We found that lower SES and peripheral residence were associated with deleterious outcomes in IBD. This should be considered by policymakers and should encourage strategies for improving outcomes in populations at risk.

In a novel nationwide population study, we found that patients with inflammatory bowel disease living in peripheral regions and those with lower socioeconomic status had significantly worse inflammatory bowel disease outcomes, notably higher corticosteroid dependency, higher surgery rate, and higher repeat surgery rate.

Validation of predictive models for disease outcomes in paediatric ulcerative colitis: A multicentre prospective inception cohort.

BACKGROUND: Several studies have proposed models to predict disease outcomes in paediatric ulcerative colitis (UC), notably PROTECT, Schechter and PIBD-ahead, but none has been validated by external cohorts AIM: To explore these models in a prospective multicentre inception cohort METHODS: Children newly diagnosed with UC in 17 centres were followed at disease onset and 3 and 12 months thereafter, as well as at last visit. Outcomes included steroid-free remission (SFR) and acute severe colitis (ASC). RESULTS: Of the 223 included children, 74 (34%), 97 (43%) and 52 (23%) presented with mild, moderate and severe disease, respectively. SFR rate was 35% at 3 months and 47% at 12 months (62% of those with mild disease at diagnosis vs. 41% in moderate-severe disease; p = 0.01). Thirty-six (16%) children developed ASC during the first month after diagnosis, and 53 (24%) during the first year. The AUC of the PROTECT model for predicting SFR at 3 and 12 months was 0.78 [95% CI 0.65-0.92] and 0.57 [95% CI 0.47-0.66], respectively. The sensitivity/specificity/PPV/NPV of Schechter's criteria to predict sustained SFR at 12 months was 50%/60%/35%/74%. ASC was predicted only by the PUCAI score at diagnosis and at 3 months. CONCLUSIONS: The PROTECT model had a good predictive utility for SFR at 3 months, but not at 12 months. The other predictive models did not achieve sufficient accuracy, which was far from that reported in the original studies. This highlights the necessity for external validation of any prediction model prior to its implementation into clinical practice.

Preoperative clear fluid fasting and endoscopy-measured gastric fluid volume in children.

BACKGROUND: In light of new recommendations to shorten clear fluid fasting time before anesthesia, our study aimed at exploring residual fluid volume in the stomach after different fasting times. We intended to perform direct endoscopic aspiration of stomach contents under vision, as part of routine gastroscopy assessment. Hereby we would be able to quantify true residual gastric fluid volume and acidity in children and measure their correlation with fasting times. METHODS: The study was performed as a single-center, prospective study in pediatric perioperative day care at a university-affiliated tertiary care center. Aspiration of gastric fluid contents was performed in anesthetized children aged 1-18 years undergoing an elective gastroscopy. Recorded data included patient fast time, last meal content, last clear fluid content, and aspirated gastric volume and pH, as well as patient characteristics. RESULTS: We included 253 gastroscopies, performed in 245 children. Mean fasting time for clear fluids was 6.9 h (range 1 h 40 min - 18 h 35 min) (SD 4.5). Mean age was 9.8 years (SD 5.1) and mean body weight was 33.2 kg (SD 18.7). Mean residual gastric volume was 12 mL (0-90) (SD 13.5) or 0.34 mL/kg (SD 0.37) and mean pH was 1.5 (SD 0.9). No significant correlation was observed between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight (r = -.103, p = .1), nor between clear fluid fasting time and the pH of the residual gastric fluid (r = -.07, p = .3). In more than half of the patients the residual gastric volume was less than 10 mL, unrelated to fasting time. CONCLUSIONS: In children undergoing gastroscopy, we could not demonstrate any association between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight. Since we did not see a clinically relevant association between clear fluids fasting time and gastric residual volume, this study may support the recommendation to shorten clear fluids fasting time.

Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix.

BACKGROUND: Patients enrolled in randomised controlled trials (RCTs) may differ from the target population due to restricted eligibility criteria. AIM: To compare treatment response to biologics in routine practice for children with inflammatory bowel diseases (IBD) who would and would not have been eligible for enrolment in the regulatory RCT of the same drug. METHODS: We enrolled children with IBD who initiated adalimumab, infliximab, vedolizumab or ustekinumab. The eligibility criteria as defined in the RCT of the corresponding biologic were applied to each patient. The primary outcome was 12-month steroid-free remission (SFR) without switching biologics or undergoing surgery. RESULTS: We screened 289 children (198 [68%] with Crohn's disease [CD], 91 [32%] with ulcerative colitis [UC]) with 326 initiations of biologics. Only 62 of 164 (38%) children with moderate-to-severe disease would have been eligible for inclusion in the original RCTs. The SFR rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2-4.5]; p = 0.01). The main exclusion criterion was prohibited previous therapies (47%). Ineligible CD patients were older, more often had a family history of IBD and had higher levels of CRP than eligible children; in UC there were no differences between the groups. CONCLUSION: Most children with IBD who initiate biologics would not have been eligible to be included in the corresponding regulatory RCTs. The outcomes of ineligible patients were worse than for eligible patients. Results from RCTs should be interpreted with caution when applied to clinical practice.

The Variable Response to Teduglutide in Pediatric Short Bowel Syndrome: A Single Country Real-Life Experience.

OBJECTIVES: The glucagon-like peptide-2 analog Teduglutide has been shown to enhance intestinal absorption and decrease parenteral nutrition (PN) requirements in short bowel syndrome (SBS). As data in children is limited, we evaluated nationwide real-life experience and treatment outcome in children with SBS. METHODS: Longitudinal data of children treated with Teduglutide for ≥3 months was collected. Data included demographic and medical background, anthropometrics, laboratory assessments and PN requirements. Treatment response was defined as >20% reduction in PN requirement. RESULTS: The study included 13 patients [54% males, median (interquartile range {IQR}) age of 6 (4.7-7) years]. The most common SBS etiology was necrotizing enterocolitis (38%), and median (IQR) small bowel length was 20 (15-40) cm. Teduglutide treatment ranged between 3 and 51 months [median (IQR) of 18 (12-30) months], with 10 patients (77%) treated >1 year. Response to treatment was observed in 8 patients (62%), with a mean [±standard deviation (SD)] treatment duration of 5.9 (±3.2) months. Among responders, 2 patients were weaned off PN and additional 4 decreased PN needs by >40%. There was a median (IQR) reduction in PN volume/kg of 36% (15%-55%) and in PN energy/kg of 27% (6%-58%). Response was not associated with patients' background, and no correlation was found with bowel length or PN dependency at baseline. CONCLUSIONS: Real-life response to Teduglutide is highly variable among children with SBS. While most patients did reach 20% reduction in PN, less achieved further significant reduction or enteral autonomy. No predictive factors of response to treatment were identified, and large multicenter studies are needed to elucidate predictive factors and long-term outcome.

Retained metal fragments following esophageal button battery impaction.

Button battery (BB) impaction in the esophagus requires immediate endoscopic removal and meticulous follow-up, including serial cross-sectional imaging, preferably with magnetic resonance imaging (MRI). However, BBs quickly degrade in the esophagus, and metallic fragments may remain in the injured mucosa following removal. This metallic debris can cause thermal injury during MRI, potentially aggravating local injury. We aimed to explore whether such metallic fragments could be identified on imaging following BB removal. In this study, we conducted a retrospective review of children (0-18 years) presenting with BB impaction in the esophagus between 2014 and 2020. Endoscopy reports and imaging studies were blindly reviewed by a pediatric gastroenterologist and a pediatric radiologist. Of 161 cases of battery ingestion, 14 (8%) underwent endoscopy, and in 9 (5%) a BB was impacted in the esophagus. The median time from ingestion to BB removal was 8 h (range 2-48 h). The median time from removal to CT was 44 h (range 0.5-104 h). BB appearance ranged from mild corrosion to visible debris. Pre-removal plain films showed irregular battery contour suggesting corrosion (5/7 plain films). In 7/9 CT scans (78%), high-attenuation esophageal content (median 266HU (range 140-1151)), which may represent metallic debris, was identified. Five patients had a follow-up CT which still showed gradual resolution of the high-attenuation content.Conclusions: we describe a new finding on CT following BB removal which might represent metallic debris. Clinicians should be aware of these findings which potentially may be harmful during MRI used in the ongoing assessment of esophageal injury. What is Known: • Button batteries are a dangerous pediatric foreign body with potentially fatal vascular complications. What is New: • Metallic debris was identified on computerized tomography following button battery removal in most children. • We bring to attention this new finding which may affect clinical management, as minimal metallic content can cause burns during MRI.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN.

BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Pediatric Gastrointestinal Endoscopy: Diagnostic Yield and Appropriateness of Referral Based on Clinical Presentation: A Pilot Study.

Objectives: There is a lack of evidence-based consensus for the utility of gastrointestinal endoscopy (GIE) in an array of frequently occurring symptoms in children. We aimed to assess the diagnostic yield of endoscopy in an effort to aid clinical decision making. Methods: Retrospective analysis included patients ≤18 years who underwent GIE during one calendar year at Shaare Zedek Medical Center. We excluded children referred for predefined obvious indications for GIE, planned follow-up procedures, and therapeutic endoscopy. Clinician-assigned indication for endoscopy as well as endoscopic and histologic findings were recorded. Diagnostic yield of GIE was determined according to referral indication. Results: There were 794 endoscopies performed of which 329 were included in the analysis (mean age 9.3 ± 5.0 years, 51% female). No significant complications of GIE were recorded. Six major referral indications were identified among which abdominal pain was the most frequent 88/329 (26%) of whom 32/88 (36%) had a significant diagnostic finding. Among the other major indications, diagnostic findings were found in 36/85 (43%) children with primary indication of chronic diarrhea, 14/33 (42%) failure to thrive, 15/32 (46%) short stature, 30/56 (54%) iron deficiency, and 20/48 (42%) weight loss. Conclusions: Pediatric GIE is a safe procedure with diverse clinical indications. The diagnostic yield of endoscopy is variable, depending on the referral indication. These data can assist formulating judicious referral practices.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

Predicting Outcomes in Pediatric Ulcerative Colitis for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease-Ahead Program.

BACKGROUND & AIMS: A better understanding of prognostic factors in ulcerative colitis (UC) could improve patient management and reduce complications. We aimed to identify evidence-based predictors for outcomes in pediatric UC, which may be used to optimize treatment algorithms. METHODS: Potential outcomes worthy of prediction in UC were determined by surveying 202 experts in pediatric UC. A systematic review of the literature, with selected meta-analysis, was performed to identify studies that investigated predictors for these outcomes. Multiple national and international meetings were held to reach consensus on evidence-based statements. RESULTS: Consensus was reached on 31 statements regarding predictors of colectomy, acute severe colitis (ASC), chronically active pediatric UC, cancer and mortality. At diagnosis, disease extent (6 studies, N = 627; P = .035), Pediatric Ulcerative Colitis Activity Index score (4 studies, n = 318; P < .001), hemoglobin, hematocrit, and albumin may predict colectomy. In addition, family history of UC (2 studies, n = 557; P = .0004), extraintestinal manifestations (4 studies, n = 526; P = .048), and disease extension over time may predict colectomy, whereas primary sclerosing cholangitis (PSC) may be protective. Acute severe colitis may be predicted by disease severity at onset and hypoalbuminemia. Higher Pediatric Ulcerative Colitis Activity Index score and C-reactive protein on days 3 and 5 of hospital admission predict failure of intravenous steroids. Risk factors for malignancy included concomitant diagnosis of primary sclerosing cholangitis, longstanding colitis (>10 years), male sex, and younger age at diagnosis. CONCLUSIONS: These evidence-based consensus statements offer predictions to be considered for a personalized medicine approach in treating pediatric UC.

Clinical Criteria Can Identify Children With Osteopenia in Newly Diagnosed Crohn Disease.

OBJECTIVES: Chronic inflammation of Crohn disease (CD) is associated with reduced bone mineral density (BMD). As bone mass is almost exclusively accrued during childhood, early recognition of osteopenia is especially important in pediatric CD. We aimed to identify variables associated with osteopenia to guide dual-energy X-ray absorptiometry (DXA) scan screening to those who most need it. METHODS: This was a retrospective inception cohort study of children newly diagnosed with CD, and routinely referred to DXA scans. Demographic and explicit clinical data were recorded along with whole-body less head BMD, adjusted for age, sex, and height by z-scores. RESULTS: Of the 116 included children (mean age 13 ±â€Š3.1 years, 67 [58%] boys, mean body mass index [BMI] 16.7 ±â€Š2.6), 63 (54%) had normal BMD (z-score > -1) or borderline osteopenia (-1 ≥ z-score > -2) and 53 (46%) had osteopenia (z-score ≤ -2). Osteopenia was associated with lower BMI z-score (-0.8 ±â€Š1.2 vs -1.8 ±â€Š1.1, P < 0.001) and higher PCDAI (33.7 ±â€Š15.2 vs 25.7 ±â€Š16.5; P = 0.009) than those with BMD z-score >-2. In total, 59% of children with BMI z-score <-0.5 had moderate-severe osteopenia and only 18% of those with higher z-scores. Multivariate logistic regression identified BMI z-score as the sole risk factor (OR 1.28 [95% CI 1.08-1.52], P = 0.005). BMI z-score ≥-0.5 excludes osteopenia with a sensitivity 87%, specificity 49%, NPV 82%, and PPV 59%. CONCLUSIONS: Osteopenia was found in nearly half of children with newly onset CD. BMI z-score <-0.5 should prompt referral to DXA screening.

Predicting Outcomes in Pediatric Crohn's Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease-Ahead Program.

BACKGROUND & AIMS: A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. METHODS: A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. RESULTS: Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. CONCLUSIONS: These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.

Multisystem Inflammatory Syndrome in Children Associated With Severe Acute Respiratory Syndrome Coronavirus-2 in an 8-Week-Old Infant.

We describe an 8-week-old infant with severe gastrointestinal symptoms, significant hypoalbuminemia, and mild carditis following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infant's symptoms, including their temporal appearance, were consistent with multisystem inflammatory syndrome in children (MIS-C). A unique finding on colonic histology which may shed light on the pathogenesis of MIS-C was identified. The patient improved significantly following several anti-inflammatory treatments. The lag between the presentation of MIS-C and initial SARS-CoV-2 exposure, which may often be asymptomatic, together with the young age of our patient, makes this a challenging diagnosis. Clinicians should be aware of this entity, even in the neonatal and infantile age groups, to facilitate timely identification and treatment.

Early Feeding in Acute Pancreatitis in Children: A Randomized Controlled Trial.

BACKGROUND: Studies have increasingly challenged the traditional management of acute pancreatitis (AP) with bowel rest. However, these studies used a low-fat diet or transgastric feeding and only included adults. Aiming to generate higher-quality prospective pediatric data, we compared the traditional approach of fasting and intravenous fluids and early enteral feeding with standard diet or formula. METHODS: Randomized controlled trial of children (2-18 years) with mild-moderate AP. Patients were randomly assigned 1:1 to initial fasting and intravenous fluids or an immediate, unrestricted diet. Pain scores, blood measures, and cross-sectional imaging were recorded throughout admission and follow-up. The primary outcome was time to discharge, and secondary outcomes were clinical and biochemical resolution and local and systemic complication rates. RESULTS: Of 33 patients (17 [52%] boys, mean age of 11.5 [±4.8] years), 18 (55%) were randomly assigned to early feeding and 15 (45%) were randomly assigned to initial fasting. We recorded the median (interquartile range [IQR]) time to discharge (2.6 [IQR 2.0 to 4.0] vs 2.9 [IQR 1.8 to 5.6]; P = .95), reduction in serum lipase levels by day 2 (58% [IQR 2% to 85%] vs 48% [IQR 3% to 71%]; P = .65), and readmission rates (1 of 18 [6%] vs 2 of 15 [13%]; P = .22) between the early feeding and fasting cohorts, respectively. Immediate or delayed complication rates did not differ. Patients randomly assigned to early feeding had weight gain of 1.3 kg (IQR 0.29 to 3.6) at follow-up, compared with weight loss of 0.8 kg (IQR -2.1 to 0.7) in fasted patients (P = .028). CONCLUSIONS: This is the first randomized controlled trial in pediatric AP. There was no difference between early commencement of a standard oral diet and initial fast in any of the major outcome measures.

Outcomes Following Pouch Formation in Paediatric Ulcerative Colitis: A Study From the Porto Group of ESPGHAN.

INTRODUCTION: Contemporary pediatric data on pouch outcomes are sparse, especially in the era of laparoscopic surgeries. We aimed to assess outcomes and predictors in children with ulcerative colitis/inflammatory bowel disease (IBD)-unclassified who underwent colectomy and ileal pouch-anal anastomosis. METHODS: This was a multicenter retrospective cohort study from 17 IBD centers affiliated with the pediatric IBD Porto group of ESPGHAN. An electronic REDcap system was used to collate baseline characteristics, demographic, clinical, management and surgical data, short- and long-term outcomes, and to identify potential predictors of pouch outcome. RESULTS: Of the 129 patients included, 86 (67%) developed pouchitis during follow-up of median 40 months (interquartile range 26-72), of whom 33 (26%) with chronic pouchitis. Patients operated on by surgeons performing <10 pouch surgeries/year had a higher rate of chronic pouchitis (11/27 [41%] vs 8/54 [15%], P = 0.013) on both univariable and multivariable analyses and also associated with time to pouchitis (P = 0.018) and chronic pouchitis (P = 0.020). At last follow-up, overall pouch performance was rated good/excellent in 86 (74%) patients. Time from colectomy to pouch formation was not associated with pouch outcomes. Despite higher rate of nonsevere surgical complications among children undergoing colectomy at <10 years of age (7/16 [44%] vs 10/92 [11%], P = 0.003), functional outcome and pouchitis rate did not differ. CONCLUSIONS: Pouchitis rate in children with ulcerative colitis/IBD unclassified is high. Surgeon experience is the major modifiable risk factor for pouch outcome. Our analyses suggest that pouch surgery can also be performed successfully in young children.

Appraisal of the PIBD-classes Criteria: A Multicentre Validation.

INTRODUCTION: The PIBD-classes criteria were developed to standardise the classification of children with inflammatory bowel disease [IBD], from Crohn's disease [CD], through IBD-unclassified [IBD-U], to typical ulcerative colitis [UC]. We aimed to further validate the criteria and to explore possible modifications. METHODS: This was a multicentre retrospective cohort study of children diagnosed with IBD with at least 1 year of follow-up. Clinical, radiological, endoscopic, and histological data were recorded at diagnosis and latest follow-up, as well as the 23 items of the PIBD-classes criteria. The PIBD-classes criteria were assessed for redundant items, and a simplified algorithm was proposed and validated on the original derivation cohort from which the PIBD-classes algorithm was derived. RESULTS: Of the 184 included children [age at diagnosis 13 ± 3 years, 55% males], 122 [66%] were diagnosed by the physician with CD, 17 [9%] with IBD-U, and 45 [25%] with UC. There was high agreement between physician-assigned and PIBD-classes generated diagnosis for CD [93%; eight patients moved to IBD-U] and for UC [84%; six moved to IBD-U and one to CD]. A simplified version of the algorithm with only 19 items is suggested, with comparable performance to the original algorithm [81% sensitivity and 81% specificity vs 78% and 83% for UC; and 79% and 95% vs 80% and 95% for CD, respectively]. CONCLUSIONS: The PIBD-classes algorithm is a useful tool to facilitate standardised objective classification of IBD subtypes in children. A modified version of the PIBD-classes maintains accuracy of classification with a simplified algorithm.

Antibiotic Cocktail for Pediatric Acute Severe Colitis and the Microbiome: The PRASCO Randomized Controlled Trial.

BACKGROUND: Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC). METHODS: Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome. RESULTS: Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ±â€…4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ±â€…16.7 vs 40.4 ±â€…20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm. CONCLUSION: Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).

Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.