This phase 3, multicenter, randomized, open-label study (NCT05126901) compared oral ferric maltol with ferrous sulfate, across 23 sites in the US and the UK, evaluating the safety, efficacy, pharmacokinetics, tolerability, and palatability of age-specific doses in infants, children and, adolescents with iron deficiency anemia (IDA). In a 12-week study, a total of 61 children/adolescents aged 2–17 years (median age 14 years; 45 female patients [73.8

BACKGROUND:Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. OBJECTIVE:To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. METHODS:Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3 months later in children with IBD. RESULTS:In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3 years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p < 0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p < 0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p = 0.001) and UC (p = 0.012) compared with controls and decreased following treatment in UC (p = 0.01). In CD, propan-1-ol was significantly greater than controls (p < 0.001) and extensive colitis (p = 0.001) and fell with treatment (p = 0.05). Phenol was significantly greater in CD (p < 0.001) and fell with treatment in both CD (p = 0.02) and UC (p = 0.01). CONCLUSION:Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.

INTRODUCTION:Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS:A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS:A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION:Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

BACKGROUND:Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS:Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS:In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS:113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION:Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

Objective To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.Methods A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical ‘how to prepare and use’ OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.Results 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed.Conclusion A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.

Eosinophilic oesophagitis is now being diagnosed more often, although there continues to be a significant delay in the recognition of the condition in primary care, and among patients presenting with food bolus obstruction to other specialities like Ears, Nose and Throat and Accident & Emergency. The diagnosis requires endoscopy and biopsy, with six biopsies taken from at least two different areas of the oesophagus. The diagnostic threshold is > 15 eosinophils/high power field or 0.3 mm2. Dietary management although effective is often difficult to carry out due to poor adherence by patients and the need for a specialist dietitian and repeated biopsies. Orodispersible budesonide is very effective for inducing remission and maintaining it long term, with fewer biopsies. Newer targeted biological agents are promising in the treatment of patients who have not responded to conventional treatments. Dilatation of strictures in this condition is safe.

Introduction Anterior abdominal wall blocks (AAWB), including rectus sheath (RSB) and transverse abdominis plane (TAP) blocks are frequently used in surgical procedures including umbilical hernia repair and midline incision operations. AAWB is a well-recognised method of post-operative pain management. The European Society of Anaesthesiology 2018, recommends the use of local infiltration with a long-acting anaesthetic agent and an anterior abdominal wall block (RSB/TAP) in laparotomy where resources permit. Limited information is available for the use of AAWB blocks in pain management for paediatric percutaneous endoscopic gastrostomy insertion (PEG). Aim This project intended to compare the outcomes following use of AAWB and local anaesthetic in paediatric PEG insertions compared to local anaesthetic (LA) alone. Primary outcomes measures were post-operative pain scores, breakthrough pain management during the first 12 hours post-procedure and length of hospital admission. Method Patients undergoing Gastroenterology-inserted PEG were identified through operator diaries between November 2020 to November 2021. Records were reviewed to evaluate intra-operative analgesic agents, post-operative pain scores at 1, 4, 8 and 12 hours post-procedure and length of hospital stay. Results 30 patients were identified. 18 received LA alone (bupivacaine, levobupivacaine or chirocaine) and 12 received combined pain management with LA and AAWB. Age range of patients was similar in the LA and combined groups (3 – 128 months and 4 - 170 months). Indication for gastrostomy were similar in both groups; faltering growth (11, 5), NG dependence (9, 6), unsafe swallow/feeding difficulties (5, 3). The average length of stay was longer in those with LA alone [2.2 (1 to 5 days)] compared to the combined group [1.9 (1 to 6 days)]. Discharge on day 1 was lower in LA compared to the combined group (38.9%, 58.3%), similar on day 2 (27.7%, 25%) and a higher proportion stayed for greater than 3 days (33.3%, 16.7%). Breakthrough pain relief during the first twelve hours post-procedure included intravenous morphine (5.6% [LA] versus 0%[combined]), oral morphine (27.8% [LA] versus 16.7% [combined]), intravenous paracetamol (33.3% [LA] vs 58.3%[combined]), oral paracetamol (72.2% [LA] vs 75% [combined]), ibuprofen (33.3% [LA] vs 50%[combined]) and rectal diclofenac (5.6% [LA] vs 8.3%[combined]). Positive pain scores at 1, 4, 8 and 12 hours were similar; LA [16.7%, 16.7%, 11.1%, 0%] and combined [16.7%, 25%, 8.3%, 8.3%]. Conclusion On average patients who had AAWB had a reduced length of stay and were more likely to be discharged on day 1. This is also shown in patients who stayed for two or more days. The results have shown a lower requirement of intravenous opiates in patients with AAWB compared to those who had a local anaesthetic. Use of non-opiate pain relief was similar in both groups. This might reflect standard pain management protocol. Assessment of pain scoring was similar across both groups. However, pain scoring is subjective and can be difficult to standardise amongst clinicians. Our sample size is currently restricted to 30 patients. We plan to expand our data collection to prospectively evaluate outcomes associated with AAWB versus LA alone, prior to its uniform implementation in practice.

Introduction/Background Clinical symptoms of children with organic, functional, and eosinophilic disease overlap. It is therefore imperative to establish guidance on reference values which numbers of mucosal eosinophils (eos) in the gastrointestinal (GI) tract of children without an organic disease are considered normal. In contrast to eosinophilic oesophagitis, other eosinophilic gastrointestinal diseases (EGIDs) are currently not well defined and evidence-based treatment requires definition of which eosinophil numbers are considered pathological. Aim To assess the peak number of eosinophils in each segment of the GI tract in ''healthy'' children who have not been diagnosed with an organic disease within at least one year post endoscopy and had either spontaneous resolution of symptoms or were diagnosed with functional GI disorders (FGIDs) as per Rome criteria. Methods Retrospective study of a tertiary UK paediatric centre, as part of European collaborative project. Patients with macroscopically normal endoscopy and no underlying diagnosis of inflammatory bowel disease, coeliac disease, parasitic infection, or other defined disorders were included. All biopsies were reviewed by a single pathologist and critically reviewed by a second pathologist. The formula: eos/mm²= (eos/HPF) x(1/area of microscope HPF in mm²) was used to standardise the results. Results We identified 65 patients (males: n=36, 55%) with median age 13.3 (range 1.5 – 16.5) years who underwent endoscopy between January 2017 and December 2018. The commonest reasons for endoscopy were abdominal pain (89%), followed by diarrhoea (58%) and faltering growth (20%), upon referral; a history of atopy was reported for n=6 patients (9%). Majority of patients (n=42, 65%) were diagnosed with a FGID at the last follow up, whereas spontaneous resolution of symptoms was reported in 23 patients (35%). No histological features of eosinophil activation were noted in this cohort, and age was not a discriminatory factor. Peak eosinophilic concentrations (IQR, eos/hpf, table 1) were: oesophagus 0–0, stomach 0–1, duodenal bulb 8–14, second part of duodenum 3–9, terminal ileum 6–13, caecum 11–23, ascending colon 9–21, transverse colon 5–17, descending colon 5–14, sigmoid 4–12, rectum 1–7; however, numbers were higher in outliers. The peak density of eosinophils, as shown on figure 1, increased progressively from oesophagus to caecum, and then steadily decreased towards the rectum. Importantly, there were no significant differences in eosinophil density between patients with and without FGIDs. Summary/Conclusions We conducted the first cohort study from the UK illustrating median and peak concentration of eosinophils in each segment of the GI tract in healthy children since Behjati et al described paediatric eosinophilic colitis in 2009. In accordance with our European partners, we recommend a standardised way of reporting eosinophil density (eos/mm²) for use in histological analysis; this allows for objective comparisons to be made and benchmarking between different centres. The prevalence of EGID for different sections of the GI tract ranges from 3.8–8.5/100,000 and exerts a substantial burden to patients and families. Evidence-based quantitative assessment of eosinophils in the intestine provides a pivotal tool to guide clinicians for rational decision making in differential diagnosis and management of mucosal, functional, and organic diseases of the GI tract.

Background Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. Methods The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. Results Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. Conclusions These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in similar to 70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P<4x10(-10)), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P<5x10(-10)). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.