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Background: Fecal Calprotectin (FC) is a validated screening test for intestinal inflammation in Crohn's disease (CD). The objective of the study was to prospectively evaluate the limitations of FC for identifying CD in newly diagnosed untreated pediatric patients and to assess the association of FC levels with disease location and serum inflammatory markers. Methods: Consecutive children with new onset untreated CD participating in the ongoing ESPGHAN GROWTH CD study were evaluated at diagnosis for disease activity, extent, C-reactive protein (CRP), and FC. Results: In all, 60 children met the inclusion criteria (mean age 12.6 ± 4.6 years,), 25 (42%) with mild disease, 17 (28%) moderate disease, and 18 (30%) severe disease. Twenty-seven (45%) had small bowel disease only. Median FC levels did not differ between children with small bowel only (2198 μg/g interquartile range [IQR] 696–2400) and those with colonic involvement (with or without small bowel disease; 2400 μg/g (IQR 475–2400) (P = 0.76). FC was elevated in 95% of patients, in comparison to CRP (86%) and erythrocyte sedimentation rate (ESR) (83%). Three children (5%) who had normal calprotectin levels also had low or normal CRP and/or ESR. There was no correlation between calprotectin levels and either the pediatric CD activity index (r = −0.11; P = 0.94) or physicians global assessment. Conclusions: FC levels in active disease confined to the small bowel were elevated in the vast majority of children and site of disease was not a confounding factor in this setting. Patients with low FC had a trend toward low levels of inflammatory markers as well. We did not find a significant correlation between FC and clinical indices of activity (Inflamm Bowel Dis 2012)

International audience; BACKGROUND. Patients with ulcerative colitis (UC) often receive thiopurines as immunomodulators (IMs) to maintain remission and avoid corticosteroids (CS). If unresponsive or intolerant to these agents they are treated with methotrexate (MTX), an antimetabolite never assessed in pediatric UC. AIM. To describe the experience with MTX in UC children METHODS. Thirty-two patients (median age 13.9 years) received MTX. Pediatric Ulcerative Colitis Activity Index (PUCAI) and use of CS were the main outcomes evaluated baseline and at 3, 6 and 12 months. RESULTS. Indications to MTX were azathioprine (AZA) unresponsiveness in 18, AZA intolerance/toxicity in 10 and spondyloarthropathy in 4. Response or remission were achieved in 72%, 63% and 50% of patients at 3, 6 and 12 months, respectively. Mean PUCAI was 49.5±23.3 at baseline and 32.9±21.9, 29.5±21.8 and 29.4±19.9 at 3,6 and 12 months, respectively (p: 0.03). At the beginning of MTX 16 patients (50%) received CS, that were discontinued in 13 of them (81%) by 6 months. At the end of the study 11 patients (33%) needed short courses of CS for disease relapse. CONCLUSIONS. MTX may be useful in treating children with UC, although large, controlled trials are warranted to better define its effectiveness in pediatric UC.

OBJECTIVES: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.

Background: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. Methods: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. Results: A total of 147 children [mean age 12.9 +/- 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], p = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 +/- 1 months with CS, 16.05 +/- 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 +/- 1.1 to -0.51 +/- 1.2, p = 0.01], but not with EEN [-0.32 +/- 1.1 to -0.22 +/- 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. Conclusions: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD.

Background Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. Aim To develop predictive models for early relapse following first remission. Methods The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. Results We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. Conclusions Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.

Through genomic analysis of mucosa-associated Escherichia coli strains, we found a close genetic association among isolates from pediatric inflammatory bowel disease (IBD) patients. A specific E. coli pathovar, adherent–invasive E. coli (AIEC), was found in Crohn’s disease (CD) adult patients — this pathovar has enhanced adhesive and invasive properties, mainly due to the mannose-bonding FimH protein. We aimed to characterize 52 mucosa-associated E. coli strains isolated from pediatric IBD and non-IBD patients. Eleven E. coli strains, showing a strong similarity in fimH gene sequence to that of E. coli AIEC LF82, were characterized for fimH gene sequence, genomic profiling, adhesive and invasive ability, and phylogrouping. The results were compared with E. coli strains AIEC LF82 and MG1655. The 11 E. coli isolates showed 82.4% ± 1.4% fimH sequence similarity and 80.6% ± 1.3% genomic similarity to strain AIEC LF82. All these strains harbored V27A and S78N FimH mutations, as found in LF82. Nine of them belonged to the more virulent B2 and D phylogroups. Neuraminidase treatment, mimicking inflamed mucosa, enhanced adhesion of all 11 strains by 3.5-fold, but none showed invasion ability. It could be argued that the 11 selected strains could be a branch of an E. coli subpopulation (pathobionts), that could take advantage in an inflamed context because of a suitable genomic and (or) genetic backdrop.