Magnetic Resonance Enterography Cannot Replace Upper Endoscopy in Pediatric Crohn Disease: An Imagekids Sub-study

Objectives: Although magnetic resonance enterography (MRE) can accurately reflect ileal inflammation in pediatric Crohn disease (CD), there are no pediatric data on the accuracy of MRE to detect upper gastrointestinal tract (UGI) lesions. We aimed to compare MRE and esophagogastroduodenoscopy (EGD) in detecting the spectrum and severity of UGI disease in children. Methods: This is an ancillary study of the prospective multi-center ImageKids study focusing on pediatric MRE. EGD was performed within 2 weeks of MRE (at disease onset or thereafter) and explicitly scored by SES-CD modified for the UGI and physician global assessment. Local and central radiologists scored the UGI region of the MRE blinded to the EGD. Accuracy of MRE compared with EGD was examined using correlational coefficients (r) and area under receiver operating characteristic curves (AUC). Results: One hundred and eighty-eight patients were reviewed (mean age 14 +/- 1 years, 103 [55%] boys);66 of 188 (35%) children had macroscopic ulcerations on EGD (esophagus, 13 [7%];stomach, 34 [18%];duodenum, 45 [24%]). Most children had aphthous ulcers, but 10 (5%) had larger ulcers (stomach, 2 [1%];duodenum, 8 [4%]). There was no agreement between local and central radiologists on the presence or absence of UGI inflammation on MRE (Kappa=0.02, P - 0.71). EGD findings were not accurately detected by MRE, read locally or centrally (r=-0.03 to 0.11, P = 0.18-0.88;AUC - 0.47-0.55, P = 0.53-1.00).No fistulae or narrowings were identified on either EGD or MRE. Conclusions: MRE cannot reliably assess the UGI in pediatric CD and cannot replace EGD for this purpose

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 +/- 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 +/- 16.7 vs 40.4 +/- 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.Peer reviewe

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

Once-Versus Twice-daily Mesalazine to Induce Remission in Paediatric Ulcerative Colitis : A Randomised Controlled Trial

Background: Trials in adults suggested that, in ulcerative colitis [UC], once-daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective than twice-daily [BD] dosing. In this induction of remission, investigator-blinded, randomised controlled-trial, we aimed to compare effectiveness and safety of once-versus twice-daily mesalazine in paediatric UC. Methods: Children, aged 4-18 years with a PUCAI [Paediatric Ulcerative Colitis Activity Index] of 10-55 points at inclusion, were randomised in blocks of six with blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The primary outcome was mean PUCAI score at Week 6. Results: A total of 83/86 randomised children were eligible and analysed: 43 in the OD group and 40 in the BD group (mean age 14 +/- 2.7 years, 43 [52%] males, 51 [62%] extensive colitis). The groups did not differ with regard to disease activity or any other parameter at baseline. There was no difference in median PUCAI score between the OD group and BD group at Week 6: 15 (interquartile range [IQR] 5-40) versus 10 [0-40]; p = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78]. Proportion of children in remission [PUCAI 0.2]. Conclusions: In this first randomised controlled trial in children, no differences were found between OD and BD dosing for any clinical outcome. Remission was achieved in 35% of children treated with mesalazine for active UC.Peer reviewe

Oral Vancomycin and Gentamicin for Treatment of Very Early Onset Inflammatory Bowel Disease.

10.1159/000475660Digestion954310-31

Anti-TNFα treatment after surgical resection for Crohn's disease is effective despite previous pharmacodynamic failure

Background: The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNF alpha) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNF alpha agent postoperatively. Methods: Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNF alpha agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNF alpha pharmacodynamic failure and those with no preoperative antiTNF alpha treatment. Results: A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNF alpha initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNF alpha initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNF alpha treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNF alpha treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNF alpha treatment. Conclusions: Pediatric patients with Crohn's disease who failed anti-TNF alpha therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNF alpha naive patients

Mesalamine Enemas for Induction of Remission in Oral Mesalamine-refractory Pediatric Ulcerative Colitis : A Prospective Cohort Study

Background: Paediatric ulcerative colitis [UC] is more extensive than adult disease, and more often refractory to mesalamine. However, no prospective trials have evaluated mesalamine enemas for inducing remission in children. Our goal was to evaluate the ability of mesalamine enemas to induce remission in mild to moderate paediatric UC refractory to oral mesalamine. Methods: This was an open-label arm of a previously reported randomised controlled trial of once-daily mesalamine in active paediatric UC [MUPPIT trial]. Children aged 4-18 years, with a Paediatric Ulcerative Colitis Activity Index [PUCAI] score of 10-55, were enrolled after failing at least 3 weeks of full-dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa (R) enemas 25 mg/kg [up to 1g] daily for 3 weeks with the previous oral dose. The primary endpoint was clinical remission by Week 3. Results: A total of 38 children were enrolled (mean age 14.6 +/- 2.3 years; 17/38 [45%] with extensive colitis). Clinical remission was obtained in 16 [42%] and response was obtained in 27 [71%] at Week 3. Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission, including disease extent [43% in left-sided and 41% in extensive colitis] and disease activity [44% in mild and 41% in moderate activity]. Conclusion: Clinical remission can be markedly increased in children who are refractory to oral mesalamaine by adding mesalamine enemas for 3 weeks, before commencing steroids.Peer reviewe