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Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients p p n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (

Background & Aims Increased intestinal permeability has been associated with Crohn’s disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD. Methods We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6–35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR. Results An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64–5.63; P = 3.97 × 10–4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051–2.50; P = .029). Conclusions Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

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.

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.

Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center-based variation in use and diversity in practice, we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy.This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Pediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the Pediatric Gastrointestinal-Bulletin Board (PEDGI-BB). Data were collected into REDCap and analyzed using descriptive statistics.In total, 146 participants from 26 countries completed the survey. Sixty-five percentage of participants were general, non-inflammatory bowel diseases (IBD)-focused pediatric gastroenterologists, 21% were IBD-focused, and 10% were dietitians. The most common indications (∼90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial enteral nutrition (EN) after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage.We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing.

Background: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with similar to 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 modem management strategies while maintaining vigilance around appropriate outcomes and safety issues.

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 Mucosal healing is now preferred over clinical remission as a target endpoint in the treatment of Ulcerative Colitis (UC) as it has been demonstrated to reduce hospitalisation and corticosteroid use, to reduce the risk of colectomy and to reduce the risk of colorectal cancer. In routine practice, the activity and severity of UC is based on combined clinical and endoscopic assessment in addition to histology. However, it is not clear whether the currently available histologic indices can help predict disease course and treatments. Mucosal atrophy (MA) describes a state of extensive mucosal architectural damage, causing irregularities in the morphology and distribution of the intestinal glands of the mucosa. The aim of this study was to investigate the prevalence of MA in a paediatric cohort of newly diagnosed patients with UC and evaluate the relationship between the presence of MA, disease activity and treatments. Methods Children Results 176 patients with UC were included of which 21 (12%) had MA on biopsy at diagnosis (mean age 11.9 years, 51% female). Those with MA had higher PUCAI scores at three month (p=0.04), six month (p=0.01) and two year (p=0.01) follow up. MA patients had significantly higher rates of progression to immunomodulators (58% vs 44%) and biologics (25% vs 11%), were more likely to have a clinical relapse (p=0.04) and had shorter times to first relapse post diagnosis (p=0.01). Conclusion Children with UC and mucosal atrophy demonstrate a more severe disease course with higher disease activity scores and rates of relapse, which results in increased rates of progression to more intensive therapies. Further research into the mechanisms underlying the more severe disease course of mucosal atrophy patients is warranted.

Pain, irritability and feeding intolerance are common symptoms affecting quality of life in children with severe neurological impairment (SNI). We performed a retrospective study to explore the use of gabapentinoid medications for symptom control in children with SNI. Patients attending the palliative care or gastroenterology department being treated with gabapentin for irritability, vomiting or pain of unknown origin were included. Information was gathered retrospectively from medical documentation. Irritability was reduced in 30 of the 42 patients included. Gabapentin was discontinued in 15 children, 12 of whom then received pregabalin. Three children had a good response to pregabalin, six a minimal improvement and three no improvement. These results support the use of gabapentinoids in this patient cohort.

Background and AimAcute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC.MethodsThis retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged ResultsOf the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin ConclusionsHigh colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

Background/objectives: Exclusive enteral nutrition (EEN) is a safe and effective treatment modality for inducing remission in paediatric Crohn's disease (CD). The primary aim of this study was to compare the outcomes of EEN to corticosteroid (CS) therapy in newly diagnosed, treatment-naïve patients with CD. A secondary aim was to describe the outcomes of EEN in a national cohort of paediatric CD patients over a 10-year period. Subjects/methods: A retrospective chart review was conducted at the Irish national referral centre for paediatric CD. A case-matched analysis was conducted on two cohorts matched for age, gender, disease location, disease behaviour and disease activity, who received CS or EEN as their initial treatment. Subsequently, cohort analysis was conducted on all patients who undertook a course of EEN therapy between 2004 and 2013. Results: The case-matched analysis found higher remission rates after treatment with EEN (24/28, 86%) compared with those with CS (15/28, 54%; P=0.02). Dietetic contacts were found to be pivotal to the success of treatment and the attainment of remission. In total, 59 patients completed EEN at some time-point in their disease course and were included in the cohort analysis. Sixty-nine per cent of this cohort entered clinical remission (41/59). EEN was found to be most effective when used as an initial treatment (P=0.004) and less effective in patients aged under 10 years (P=0.04). Conclusions: EEN should be strongly considered as a favourable primary treatment over CS, especially in those diagnosed over the age of 10 years.

BACKGROUND: In accordance with recent regulatory guidance which mandates patient reported outcomes (PRO) [without a proxy] for use in clinical trials, elucidating the signs and symptoms that children with Crohn’s disease deem important when referencing their level of disease activity is important. AIMS: We now report the first stage in developing the TUMMY-CD index, a PRO for pediatric Crohn’s disease. METHODS: Concept elicitation interviews were performed with children and teens who have Crohn’s disease and their caregivers in 9 international centers (Canada, USA, Ireland, UK, Israel). Interviews were recorded, transcribed verbatim, and analysed using qualitative analytic techniques. Items were ranked based on frequency of endorsement and rated level of importance according to participants. Items endorsed in over 6% of participants will be carried forward to Phase 2 of study. Disease activity was categorized using the Pediatric Crohn’s Disease Activity Index (PCDAI). RESULTS: A population of 59 children aged 4–17 years (52% male, 80% inactive disease, 14% mild disease, 6% moderate to severe disease), and 56 caregivers were interviewed. Of the signs and symptoms reported, 13 were endorsed in over 6% of participants in either the child or caregiver group. The items that will be explored in the next phase of this study, in decreasing order of endorsement are: Abdominal pain (100% child, 83% caregiver), Diarrhea (53% child, 54% caregiver), Fatigue (49% child, 63% caregiver), Appetite (25% child, 36% caregiver), Nausea +/- Vomiting (24% child, 20% caregiver), Bloody Stool (20% child, 34% caregiver), Joint Pain (14% child, 27% caregiver), Weight loss (9% child, 14% caregiver), Perianal Disease (7% child, 4% caregiver), Constipation (5% child, 7% caregiver), Mood (3% child, 13% caregiver), Pallor (3% child, 11% caregiver), and Mouth Sores (3% child, 9% caregiver). No significant difference was found in the symptoms reported by children experiencing higher or lower disease activity, complicated [penetrating and/or stricturing] versus inflammatory disease behavior, or among caregivers with varying levels of education. Children under 7 years had difficulty reporting symptoms, and therefore an Observer Reported Outcome (ObsRO) will be created for this group. CONCLUSIONS: From this first stage of the development of the TUMMY-CD Index, 13 signs and symptoms were significantly endorsed by children with Crohn’s disease and their caregivers. These items will be explored in a second phase, where vocabulary and response options will be determined. Once validated, the TUMMY-CD Index can supplement objective outcome measures in future clinical trials. FUNDING AGENCIES: NASPGHAN Foundation; Investigator-initiated Grant from AbbVie

BACKGROUND AND AIM: Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS: A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION: These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

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.

Background The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a noninvasive clinician-based index, which reflects disease severity in pediatric ulcerative colitis (UC) when no endoscopy is performed. Here, we aimed to explore signs and symptoms important to children with UC and their caregivers as the first stage of developing a patient-reported outcome (PRO) measure for pediatric UC (ie, the TUMMY-UC index) to supplement endoscopic assessment. Methods Concept elicitation qualitative interviews were performed with children who have UC and their caregivers in 6 centers. Items were rank-ordered by the interviewees according to the frequency of endorsement and importance, graded on a 1 to 5 scale. Results A total of 46 children (ages 12.5 ± 3.3 years, range 7-18, 48% boys, 83% with pancolitis, 24% with moderate-severe disease) and 33 caregivers were interviewed (ie, 79 interviews). The following items were identified by the children, in decreasing order of weights: abdominal pain (importance × frequency weight 3.9), rectal bleeding (3.6), stool frequency (3.0), stool consistency (3.0), general well-being/fatigue (2.9), urgency (1.9), and nocturnal stools (1.6). Two other items were scored lower: lack of appetite (1.1) and weight loss (0.6). Children 13 to 18 years comprehended adult vocabulary, children 8 to 12 years comprehended simple vocabulary, and younger children had poor understanding in completing the questions. Conclusions In this first stage of the TUMMY-UC development, items were generated and ranked by input from patients. These items are now being explored for optimal vocabulary and response options. The TUMMY-UC will supplement the PUCAI in clinical trial outcome assessment.

SummaryBackground The incidence of paediatric inflammatory bowel disease diagnosed before age 10 years is reportedly increasing, but national data are limited. Aim To characterise the epidemiology, phenotype and clinical outcomes of children diagnosed with inflammatory bowel disease before age 10 years, and compare with data from children diagnosed aged 10-16 years. Methods A review of all Irish cases of early onset inflammatory bowel disease (diagnosis

AimsTo describe the change in incidence of paediatric inflammatory bowel disease (IBD) observed at the National Centre for Paediatric Gastroenterology, Hepatology and Nutrition, and to determine whether the presenting disease phenotype and disease outcomes have changed during the past decade.MethodsThe annual incidence of IBD in Irish children aged Results406 new cases of IBD were identified. The incidence was 2.5/100 000/year in 2001, 7.3 in 2008 and 5.6 in 2010, representing a significant increase in the number of new cases of Crohn's disease (CD) and ulcerative colitis (UC). There were 238 cases of CD; 129 of UC; and 39 of IBD unclassified. Comparing groups A and B, no differences were found in disease location at diagnosis or, for CD, in its behaviour.ConclusionsThere has been a substantial and sustained increase in the incidence of childhood UC and CD in Ireland over a relatively short period of time. However, disease phenotype at diagnosis has not changed. At 2 years follow-up, CD appears to progress less frequently than in some neighbouring countries. These variations remain unexplained. Prospective longitudinal studies will help to elucidate further the epidemiology of childhood IBD.

Major upper gastrointestinal hemorrhage is an alarming clinical presentation in infants and children. Although the etiology varies according to age at presentation, the shared principles of diagnosis and management include prompt assessment, resuscitation, investigation and therapeutic intervention. Patients with portal hypertension and other significant medical comorbidities warrant special consideration and medical management. Data on the epidemiology and outcomes of children with major upper gastrointestinal hemorrhage are limited and further research to address these questions is keenly awaited.

Chronic infections of the small intestine cause significant morbidity and mortality globally. This review focuses on the recent advances in the field of our understanding of selected intestinal infections.Primary and secondary immunodeficiency increase the susceptibility to many chronic intestinal infections. Endoscopy and intestinal biopsies are central to establishing a diagnosis of these conditions. Tuberculosis (TB) remains a major global health challenge. Emerging therapeutic agents to counteract multidrug-resistant strains have shown clinical efficacy, but concerns regarding mortality remain. PCR-based diagnostic TB tests have the potential to reduce diagnostic delays, but remain to be validated for intestinal infections. Adjunctive diagnostic imaging modalities can differentiate infections from Crohn's disease with increasing accuracy. Whipple's disease remains rare, but there have been substantial advances in our understanding of the causative organism Tropheryma whipplei. Extended treatment with broad-spectrum antibiotics is effective in most cases. The narrow therapeutic window and limited armamentarium for treating invasive filamentous fungal infections contribute to their significant morbidity and high rates of mortality.The speed and accuracy of diagnosing chronic intestinal infections have improved with recent imaging and laboratory methodologies. Significant research opportunities remain for clinicians and scientists to improve the diagnostic accuracy and clinical outcomes of chronic intestinal infections.

BACKGROUND: At the time of diagnosis of Crohn’s disease there may be oral manifestations. The aim of this study was to describe the outcome for children with oral Crohn’s disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn’s Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn’s disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9–19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20–97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn’s disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn’s disease activity elsewhere in the intestinal tract.

Cryptogenic, multifocal, ulcerous and stenosing enteritis (CMUSE) is a poorly understood and exceptionally rare disease typically characterized by the presence of multifocal persistent small bowel ulceration and stenosis (1). Some of the features of CMUSE point to a vascular etiology, although to da

Helicobacter pylori is a slowly growing, gram negative microaerophilic bacterium that colonises the gastric mucosa. Cross-sectional epidemiological studies from both developed and developing countries suggest that the prevalence of H. pylori infection worldwide is declining, and may even be less than 10% in ‘westernised’ countries.1 ,2 H. pylori infection is acquired during the first decade of life and infection usually persists without treatment. Spontaneous clearance has been reported, although co-incidental antibiotic exposure may influence such ‘clearance’. H. pylori is the causative agent for diseases including peptic ulcer disease (PUD), chronic gastritis, gastric mucosa associated lymphoid tissue lymphoma and is the single-most important risk factor for developing gastric cancer.3 ,4 Putative extraintestinal associations have included refractory iron deficient anaemia, short stature and idiopathic thrombocytopenic purpura, although data supporting these associations in children must be interpreted with caution.4 ,5 The majority of children infected with H. pylori are asymptomatic. Following successful treatment, the risk of true reinfection in childhood is extremely low, at least in developed countries.6 Recrudescence describes re-colonisation with the same strain within 12 months, while re-infection refers to colonisation with a new strain, more than 12 months after eradication. Clinicians must carefully bear in mind these salient aspects of the pathogenesis and natural history of H. pylori- associated diseases as they consider whether testing their patients for H. pylori is indicated. ### Investigations for H. pylori The primary indication for investigation in children remains to diagnose the cause of significant symptoms and not simply to detect the presence of H. pylori . Testing for H. pylori is not helpful unless it alters clinical management, and consideration of the age-related pre-test probability of particular diseases (rather than infection alone) is essential. There remain certain scenarios in which screening for the presence of H. pylori is not absolutely indicated but may …

Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations ; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.

Background Small intestinal biopsy remains the reference standard for diagnosing coeliac disease (CD) in children. Recent international guidelines suggest that for select patients, biopsy may not be necessary. Aims The aim of this study were to: (a) correlate coeliac serology with histology findings in Irish children with a high pre test probability of the disease (b) determine if proposed changes to the CD diagnostic algorithm hold true in an Irish paediatric cohort. Methods A retrospective chart review of all cases of suspected CD that underwent endoscopy at the National Centre for Paediatric Gastroenterology, Our Lady’s Children’s Hospital from January 2004 to December 2011 was undertaken. Data retrieved included endoscopic and histologic findings, co-morbidities and serology results (where available). Results 596 patients (57% female) underwent endoscopy for suspected CD. Serology data were available for 544 (91%) patients. CD was confirmed on histology in 304 (51%) children. tTG (tissue transglutaminase) was positive in 405 (79%) patients, of whom 288 (71%) also had a positive biopsy and 7 patients (5%) with negative tTG had a positive biopsy. This result was highly significant with a p value of 0.0001. Of the available 195 positive EMA (endomysial antibody) results, 184 (94%) had a positive tTG as well. 110 of 117 children with tTG values > 20 μg/ml plus a + EmA had CD on histology. 3 of 105 (2.8%) patients with tTG >100 μg/ml had a normal histology. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value of tTG levels ranging from 2–99 were 97% (CI 95–98), 53% (CI 46–59), 71% (CI 63–75) and 95% (CI 90–98) respectively. The corresponding values for tTG levels >100 were 94% (CI 87–97), 98% (CI 93–99), 97% (CI 92–99) and 95% (CI 90–98). The PPV of tTG 2–10 μg/ml was 37%, but at 100 μg/ml, this was 97%. Conclusions Intestinal biopsy remains the reference standard for CD diagnosis. High titre serology correlates well but not perfectly with histology findings. Diagnostic accuracy rather than screening convenience is essential before prescribing a life-long gluten free diet.

Objective: To compare three devices for manual neonatal ventilation. Design: Participants performed a two minute period of ventilation using a self inflating device, an anaesthesia bag with attached manometer, and a Neopuff device. An intubated neonatal mannequin, approximating a 1 kg infant with functional lungs, was used for the study. Target ventilation variables included a rate of 40 breaths per minute, peak inspiratory pressure (PIP) of 20 cm H 2 O, and positive end expiratory pressure (PEEP) of 4 cm H 2 O. The circuit was attached to a laptop computer for data recording. Results: Thirty five participants were enrolled, including consultant neonatologists, paediatricians, and anaesthetists, paediatric and anaesthetic registrars, and neonatal nurses. The maximum PIP recorded using the self inflating bag, anaesthetic bag, and Neopuff device were 75.9, 35.5, and 22.4 cm H 2 O respectively. There were significant differences between the devices for mean PIP (30.7, 18.1, and 20.1 cm H 2 O), mean PEEP (0.2, 2.8, and 4.4 cm H 2 O), mean airway pressure (7.6, 8.5, and 10.9 cm H 2 O), % total breaths ⩽ 21 cm H 2 O PIP (39%, 92%, and 98%), and % total breaths ⩾ 30 cm H 2 O PIP (45%, 0, and 0). There was no difference between doctors and allied health professionals for the variables examined. Conclusion: The anaesthetic bag with manometer and Neopuff device both facilitate accurate and reproducible manual ventilation. Self inflating devices without modifications are not as consistent by comparison and should incorporate a manometer and a PEEP device, particularly when used for resuscitation of very low birthweight infants.

P152 Rising incidence and increasing severity of very early onset IBD in Ireland R. Wylde1 *, A. Carey2,3, B. Bourke2,3,4, A. Broderick3, S. Quinn3, M. Hamzawi3, K. Gleeson3, S. Hussey2,3,4. 1Leiden University, Leiden University Medical Centre, Leiden, Netherlands, 2National Childrens Research Centre, NCRC, Dublin, Ireland, 3Our Lady’s Childrens Hospital Crumlin, Dept. of Gastroenterology, Hepatology and Nutrition, Dublin, Ireland, 4University College Dublin (UCD), School of Medicine and Medical Science, Dublin, Ireland

evidenced by lower levels of health-related quality of life (HRQOL) especially in children with high levels of abdominal pain. Research examining psychological and social factors related to IBD and associated HRQOL is critical. For children in particular, the family environment might play a crucial role in the their coping with IBD. Dysfunctional levels of overall functioning have been associated with lower HRQOL in chidlren with IBD, yet the impact of specific aspects of family functioning, such as cohesion (i.e., emotional bond or connectiveness), flexibility (i.e., balance between stability and change) and communication patterns (i.e., postive versus negative) is largely unexplored. The purpose of the present study was to investigate the influence of balanced levels of cohesion and flexbility and positive communication on the child’s pain experience and HRQOL. Methods: Thirty children with IBD (14 girls, 16 boys; N = 20 with Crohn’s disease, N = 10 with Ulcerative colitis; Mage = 13.73, SD = 2.30 years) and one parent (25 mothers, 5 fathersMage = 46.73, SD = 6.47 years) completed questionnaires regarding child’s level of pain and interference, HRQOL (i.e., IMPACT) and family functioning (i.e., Faces IV). Results: Linear regression analyses, controlling for child age, indicated that child report of positive communication and balanced level of cohesion and flexibility were positively associated with their HRQOL. Surprisingly, no significant associations were found between child level of pain and family functioning, while the level of interference in daily functioning due to pain was negatively associated with parent report of balanced cohesion and child report of balanced flexibility and positive communication. Conclusions: The current findings indicate that parent-reported cohesion was only associated with pain-related interference, while child-reported aspects of family functioning were related to HRQOL and pain-related interference. Results also suggest that family functioning is primarily associated with HRQOL and interference in daily functioning rather than the level of pain, adding to our understanding of how family functioning relates to children’s coping with IBD and associated pain. In future research, observational assesment of family functioning (e.g., by means of a conflict-discussion task) and parentchild communication patterns when faced with their child in pain (e.g., observation of parent child interaction during an experimental pain task), will contribute to our understanding of how family functioning influences child functioning and pain experiences.

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Aims To evaluate the use of faecal calprotectin (FC) in children with suspected inflammatory bowel disease (IBD) in the previous year, and to establish if the number of negative endoscopies had been minimised without missing any cases of IBD. To assess the use of FC in established paediatric IBD. To analyse the cost benefit of the test. Methods A retrospective analysis of FC measurements carried out between 1 st October 2011 and 30 th September 2012. FC measurements were obtained from the biochemistry department. Following a computerised search of the departmental records the presenting complaint, endoscopy result if applicable, diagnosis of IBD or alternative diagnosis, and follow-up or discharge were recorded for each patient. Patients were divided into those who were scoped based on their FC value and those who were not. Established IBD patients who had a FC test as part of their disease management were treated as a separate group. Results 36 patients (55%) were not scoped. All 36 had at least one symptom indicative of IBD. 25 of these had a FC value of 200µg/g. None of these patients have been diagnosed with IBD. 17 patients were scoped (26%). 3 of these patients were diagnosed with IBD. Median FC for the group that were not scoped was 30µg/g (interquartile range (IQR) 30–760µg/g), compared with 126µg/g (IQR 52 –1,590µg/g) in the group that were scoped. 8 patients with known IBD had a FC test when they became symptomatic and all FC values were consistent with GI inflammation. Overall, there was a 38% cost saving due to 44 unnecessary endoscopies being avoided. Conclusion FC is a valuable test for excluding IBD in patients who present with abdominal pain and diarrhoea. FC can confirm relapse in symptomatic patients known to have IBD. When the test is used in these ways patients avoid an invasive procedure and the hospital is saved the cost of the endoscopy. However, guidelines are required to ensure the correct and appropriate use of this relatively new test.