ESPGHAN 56th Annual Meeting Abstracts (2024)

LONGITUDINAL FOLLOW‐UP OF HLA‐RISK AND NON‐RISK CHILDREN SCREENED FOR CELIAC DISEASE IN THE GENERAL POPULATION TO AGE 15 YEARS: CIPIS STUDY

Michaela Boström, Charlotte Brundin, Sara Björck, Daniel Agardh

Lund University, Malmo, Sweden

Objectives and Study: Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of HLA‐genotyping and tTG autoantibodies in screening of longitudinal birth cohort for celiac disease followed to age 15 years.

Methods: Included were 13,860 HLA‐DQ‐genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA‐DQB1*02 and/or DQB1*03:02 (HLA‐risk) children were compared with non‐HLA‐DQB1*02 and non‐DQB1*03:02 (HLA‐non‐risk) children. The present study re‐invited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both IgA and IgG autoantibodies against tTG were analysed separately in radiobinding assays. Persistently tTG autoantibody positive children were examined with intestinal biopsy to confirm diagnosis of celiac disease.

Results: At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA‐risk children compared with 0/1824 HLA‐non‐risk children (p<0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA‐risk children compared with 0/2167 HLA‐non‐risk children (p<0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA‐risk children positive for IgA‐tTG and/or IgG‐tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% CI: 0.4‐1.7%) HLA‐risk children were diagnosed with celiac disease compared with 0/1303 HLA‐non‐risk children (p<0.001) and 5/491 (1.0%) HLA‐risk children were negative in screenings at both 3 and 9 years of age.

Conclusions: Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA‐risk.

Contact e‐mail address: michaela.bostrom@med.lu.se

ROLE OF ER STRESS IN THE PATHOGENESIS OF CELIAC DISEASE: A KEY BIOMARKER AND A VALUABLE NEW THERAPEUTIC TARGET

Romina Monzani¹, Mara Gagliardi¹, Valentina Saverio¹, Samuele Pellizzaro², Alice Monzani¹, Silvia Saettone³, Nico Pagano³, Ivana Rabbone¹, Luigina De Leo⁴, Daniele Sblattero², Marco Corazzari⁵

¹Health Sciences, University of Piemonte Orientale, Novara, Italy, ²Life Sciences, University of Trieste, Novara, Italy, ³Ospedale Maggiore della Carità, Novara, Italy, ⁴Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, Italy, ⁵Health Science, University of Piemonte Orientale, Novara, Italy

Objectives and Study: Celiac Disease (CD) is an autoimmune disorder that primarily affects the gut of genetically predisposed individuals and is stimulated by gliadin peptides (PT) produced in the gut during the digestion of wheat gluten. Although inappropriate activation of the immune system is considered the main culprit for intestinal dysfunction and tissue damage, the interaction between PT and intestinal epithelial cells (IEC) remains a key step in the pathogenesis of CD. Therefore, understanding the molecular mechanism(s) activated in IEC exposed to PT represents a unique opportunity to define new potential therapeutic targets.

Methods: Three different models were used to investigate the molecular basis of PT‐induced damage. Caco‐2 cells were used as a 2D cell line as an in vitro model. As an ex vivo model, we used our Gut‐Ex‐Vivo System (GEVS), which allowed us to culture the intestine of mice maintained on a gluten‐free diet (> 3 generations), enabling controlled stimulation with PT and selected drugs. Finally, biopsies from paediatric CD/non‐CD patients were used to verify our results. The effects of PT and selected drugs were investigated by analysing gene and protein expression, and by ELISA or immunofluorescence.

Results: Our study demonstrated a prompt induction of ER stress upon PT exposure, through a CXCR3/PLC/IP3/IP3R axis responsible for calcium release by the ER compartment in both in vitro and ex vivo models. Importantly, inhibition/buffering of PT‐stimulated ER stress by pharmacological chaperones or inhibition of the CXCR3 →IP3R axis completely abrogated TG2 upregulation, pro‐inflammatory cytokine production and tissue damage. Finally, increased expression of ER stress markers was confirmed in biopsies from CD patients compared to non‐CD patients.

Conclusions: Overall, our analysis: i) revealed the key role played by ER stress in the pathogenesis of CD; ii) identified the molecular mechanism linking PT and ER stress induction; and iii) unveiled valuable new therapeutic targets.

Contact e‐mail address: marco.corazzari@uniupo.it

INTESTINAL ORGANOIDS AS MODEL TO STUDY THE INTERACTION WITH GLIADIN PEPTIDES

Giorgia Fontana¹, Miriana Ghirelli², Agnes Thalhammer³, Fabiana Ziberna¹, Sara Lega¹, Giuseppe Molinario², Elena Spinelli², Matteo Bramuzzo¹, Grazia Di Leo¹, Gabriele Baj³, Luigina De Leo¹

¹Pediatric Clinic, Institute for Maternal and Child Health, I.R.C.C.S. "Burlo Garofolo, Trieste, Italy, ²University of Trieste, Trieste, Italy, ³Department Of Life Sciences, Cima (advanced Microscopy Interdepartmental Center), University of Trieste, Trieste, Italy

Objectives and Study: Coeliac Disease (CD) is a complex intestinal disorder triggered by gluten intake. The role of the intestinal epithelium in the pathogenesis of CD has not been elucidated yet. Human intestinal epithelial organoid (IEO) is a good model to investigate the interaction of ingested/digested gluten with intestinal epithelium. The aims of our study are: ‐ to visualize the interaction of toxic gliadin peptides (p31‐43) with IEO from CD‐patients and controls ‐ to investigate the effects of gliadin peptides‐IEO interaction

Methods: IEO were generated from intestinal biopsies from 3 CD‐patients and 3 control subjects exploiting the power of Lgr5+ stem cells. Apical‐out organoids were treated for 5’, 15’, 4h with 50ug/ml of p31‐43 or scrambled peptide. To visualize the interaction at confocal microscope, both peptides were tagged with a fluorescent dye. To investigate the effects of the interaction, not tagged peptides were used and RNA was extracted for transcriptome analysis.

Results: IEO from both CD‐patients and controls specifically internalize p31‐43 peptide and not the scrambled one in the cytoplasm already after 5’. Interestingly, the amount of internalized peptide is treatment‐length dependent: the fluorescent signal is greater after 4h of treatment and the quantity of p31‐43 peptide in IEO from CD‐patients is greater than in ones from controls. The effects of the specific interaction of p31‐43 peptide with organoids will be evaluated by comparing gene expression profile of IEO before and after 4h of treatment.

Conclusions: This is a preliminary study demonstrating for the first time that IEO specifically internalize the toxic peptide p31‐43. IEO from CD‐patients internalise more peptide than organoids from controls, suggesting that intestinal epithelial cells from CD‐patients have higher affinity to the digested peptides of gluten. More in‐depth studies are needed to understand how and where exactly the peptide is internalized. Transcriptome analysis will elucidate genes and pathways activated after peptide internalization.

Contact e‐mail address: giorgia.fontana@burlo.trieste.it

DIETARY FIBER INTAKE DURING THE FIRST 5 YEARS IN LIFE AND RISK OF COELIAC AUTOIMMUNITY AND COELIAC DISEASE: TEDDY STUDY

Elin Hård Af Segerstad¹, Lazarus Mramba², Carin Andrén Aronsson³, Xiang Liu², Ulla Uusitalo², Jill Norris⁴, Suvi Virtanen⁵, Sibylle Koletzko⁶, Marian Rewers⁷, Jorma Toppari⁸, Richard Mcindoe⁹, Anette‐G Ziegler¹⁰, William Hagopian¹¹, Beena Akolkar¹², Jeffrey Krischer², Daniel Agardh³

¹Pediatric Research Institute, Oslo University Hospital, Oslo, Norway, ²Health Informatics Institute, University of South Florida, Tampa, FL, United States of America, ³Unit Of Celiac Disease And Diabetes, Clinical Sciences Malmö, Lund University, Malmo, Sweden, ⁴Department Of Epidemiology, Colorado School of Public Health, Denver, United States of America, ⁵Finnish Institute for Health and Welfare and Tampere University and Tampere University Hospital, Tampere, Finland, ⁶Department Of Pediatrics, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany, Munich, Germany, ⁷University of Colorado, Aurora, CO, United States of America, ⁸University of Turku and Turku University Hospital, Turku, Finland, ⁹Augusta University, Augusta, GA, United States of America, ¹⁰Technische Universität München, and Forschergruppe Diabetes e.V, Neuherberg, Germany, ¹¹Pacific Northwest Research Institute, Seattle, United States of America, ¹²National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, United States of America

Objectives and Study: High intake of dietary fiber in pregnant women has been associated with reduced risk of coeliac disease in the offspring. The aim was to investigate if fiber intake up to age 5 years was associated with later risk of coeliac disease in genetically at‐risk children.

Methods: Included were 6,399 (74%) children screened at least once for tissue transglutaminase autoantibodies (tTGA) with minimum 13 years followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Fiber intake was calculated from 3‐days food records collected biannually. Coeliac disease autoimmunity (CDA) was defined as being tTGA positive in >2 consecutive samples. Coeliac disease was defined as having a Marsh score >1 in small bowel biopsies or mean tTGA > 100 u/L in two consecutive samples. Joint modelling investigated associations between fiber intake per 2 g/1000 kcal/day with time to CDA and coeliac disease, respectively, adjusted for HLA genotype, sex, family history of coeliac disease, country, energy and gluten intake.

Results: A total of 1,254 (19.6%) children developed CDA and 441 (6.9%) children were diagnosed with coeliac disease. Fiber intake in the first 2 years of life was associated with a reduced risk of CDA (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.92, 0.96, p<0.001) and coeliac disease (HR 0.95, 95% CI 0.91, 0.99, p=0.008, Figure). Fiber intake in the first 5 years of life was associated with an increased risk of CDA (HR 1.05, 95% CI 1.01, 1.08, p=0.004) but not coeliac disease (HR 1.03, 95% CI 0.95, 1.11, p=0.536).

Conclusions: Dietary fiber intake up to age 2 years was inversely related to the risk of CDA and coeliac disease but up to age 5 years with increased risk of CDA in genetically at‐risk children, indicating a potential role of the amount and timing of dietary fiber intake in coeliac disease development.

Contact e‐mail address: elin.malmberg_malmberg_hard_af_segerstad@med.lu.se

PREGNANCY DIET QUALITY AND DIVERSITY AND RISK OF OFFSPRING COELIAC DISEASE: THE NORWEGIAN MOTHER, FATHER AND CHILD COHORT STUDY

Elin Hård Af Segerstad¹, Tiril Borge², Annie Guo³, Karl Mårild^4,5, Lars Cristian Stene⁶, Anne Lise Brantsæter⁷, Ketil Stordal⁸

¹Pediatric Research Institute, Oslo University Hospital And Celiac Disease And Diabetes Unit, Clinical Sciences, Lund University, Malmo, Sweden, ²Norwegian Institute of Public health, Oslo, Norway, ³Department Of Pediatrics, University of Gothenburg, Gothenburg, Sweden, ⁴Department Of Pediatrics, Queen Silvia Children's Hospital, Göteborg, Sweden, ⁵Department Of Pediatrics, Institution of clinical sciences, Göteborg, Sweden, ⁶Department Of Chronic Diseases, Norwegian Institute of Public health, Oslo, Norway, ⁷Department Of Food Safety, Norwegian Institute of Public health, Oslo, Norway, ⁸Department Of Pediatric Research, University of Oslo and Oslo University Hospital, Oslo, Norway

Objectives and Study: Dietary factors in pregnancy, including gluten and fiber intakes, have been suggested to influence the risk of coeliac disease (CeD) in the offspring, but the current knowledge is limited. We aimed to investigate the associations between overall pregnancy diet quality and diversity and the offspring's risk of CeD.

Methods: We included 85,122 mother‐child pairs with available data from the population‐based Norwegian Mother, Father and Child Cohort Study. CeD was captured by >2 diagnostic codes in the Norwegian Patient Registry. A validated food frequency questionnaire administered in mid‐pregnancy assessed maternal pregnancy diet. We calculated a Pregnancy Healthy Eating Index score (median 99.8, interquartile range 92.6‐106.6), reflecting diet quality, and a Diet Diversity score (median 7.0, interquartile range 6.4‐7.7) reflecting variation in major food group intakes.

Associations between pregnancy diet quality or diversity and offspring CeD were estimated using logistic regression and was adjusted for maternal age at delivery, educational level, country origin, pregnancy smoking, gluten and fiber intake, and parental CeD (adjusted odds ratio (aOR) with 95% confidence intervals (CI)). Sensitivity analyses were performed in 30,718 (45.5%) children with celiac‐permissive HLA haplotypes DQ2/DQ8.

Results: After a follow‐up to mean age 16.0 (range 12.4‐19.8) years, 1,363 children (1.6%) had been diagnosed with CeD. There was a non‐linear association with pregnancy diet quality and the risk of CeD in the offspring, with a lower risk of CeD observed both with the lowest as well as with higher diet quality (Figure). The association remained in the sensitivity analysis including only children with DQ2/DQ8. There was no linear association between pregnancy diet diversity and offspring risk of CeD (aOR 1.00, 95%CI 0.93, 1.08).

Conclusions: Pregnancy dietary quality, but not diversity, may modify the offspring's risk of CeD in the general population, however more research is needed to explain the observed association.

Contact e‐mail address: elin.malmberg_hard_af_segerstad@med.lu.se

EPIGENETICS DATA IN CHILDREN AT‐RISK FOR CELIAC DISEASE: INSIGHTS FROM A PILOT STUDY ON THE PROSPECTIVE CD‐GEMM COHORT

Carminia Marina Ingenito¹, Mariella Cuomo^2,3, Stefano Leo¹, Francesco Valitutti^1,4, Maureen Leonard^5,6, Monica Montuori⁷, Pasqua Piemontese⁸, Ruggiero Francavilla⁹, Lorenzo Norsa¹⁰, Maria Elena Lionetti¹¹, Mariella Baldassarre¹², Chiara Maria Trovato¹³, Michela Perrone⁸, Tiziana Passaro¹⁴, Naire Sansotta¹⁵, Marco Crocco¹⁶, Annalisa Morelli¹⁷, Federica Malerba¹⁶, Luca Elli¹⁸, Fernanda Cristofori⁹, Lorenzo Chiariotti^2,3, Alessio Fasano^1,5,6, Cd‐Gemm Team¹

¹European Biomedical Research Institute of Salerno, Salerno, Italy, ²CEINGE‐Biotecnologie Avanzate, Neaples, Italy, ³Department Of Molecular Medicine And Medical Biotechnology, University of Naples "Federico II", Neaples, Italy, ⁴Pediatric Clinic, Department Of Surgical And Biomedical Sciences, University of Perugia, Perugia, Italy, ⁵Pediatric Gastroenterology And Nutrition, Harvard Medical School, Mass General Hospital for Children and Division of Pediatric Gastroenterology and Nutrition, Harvard Medical School, Boston‐Massachusetts, United States of America, ⁶Celiac Research Program, Harvard Medical School, Boston‐Massachusetts, United States of America, ⁷Pediatric Gastroenterology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy, ⁸Neonatal Intensive Care Unit (NICU), Department of Mother and Infant Science, Fondazione IRCCS “Ca' Granda” Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, ⁹Pediatric Unit "Bruno Trambusti," Ospedale Pediatrico Giovanni XXIII, University of Bari, Bari, Italy, ¹⁰Pediatric Department, Ospedale dei Bambini "Vittore Buzzi", Milano, Italy, ¹¹Pediatrics, Università Politecnica delle Marche, Ancona, Italy, ¹²Neonatal Intensive Care Unit, University of Bari, Bari, Italy, ¹³Celiac Disease Referral Center, Bambino Gesù Hospital, Rome, Italy, ¹⁴Celiac Disease Referral Center, "San Giovanni di Dio e Ruggi d'Aragona" University Hospital, Pole of Cava de' Tirreni, Salerno, Italy, ¹⁵Pediatric Hepatology Gastroenterology and Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy, ¹⁶Pediatrics, IRCCS Ospedale Giannina Gaslini, Genova, Italy, ¹⁷Pediatric Training Program, University of Salerno School of Medicine, Salerno, Italy, ¹⁸Celiac Disease Referral Center, Ospedale Maggiore Policlinico, Milan, Italy

Objectives and Study: The prospective and multicenter CD‐GEMM study has the aim to fully characterize the individual and environmental factors leading to the development of Celiac Disease (CD) with a multi‐omics approach. Here, we present the preliminary results of the epigenomics analyses conducted on a sub‐cohort of the CD‐GEMM project during the first 18 months of life.

Methods: Blood clots were collected 6, 12, and 18 months after birth from 5 CD cases and 5 controls enrolled in the CD‐GEMM study. Case‐control matching was based on age, HLA profile, delivery and feeding modes, and age at gluten introduction. DNA methylation analysis was performed with the Illumina 850k EPIC platform and the output data were processed using RnBeads software.

Results: Samples taken from celiac participants clustered together at all time points in principal component analysis plots. We identified 25,708, 12,656 and 36,868 CpG islands that were differentially methylated at 6, 12 and 18 months, respectively. In particular, the number of sites hypo‐ and hyper‐methylated in CD was 11,413‐14,295 at 6 months, 5,617‐7,039 at 12 months and 16,052‐20,816 at 18 months. This resulted in changes in DNA methylation at 192, 83 and 440 promoters at 6, 12 and 18 months, respectively. At 18 months, in CD cases, most hypomethylated promoters were of genes involved in the cysteine, methionine, carbohydrates and retinol metabolism and lactate dehydrogenase activity whereas promoters of genes involved in the regulation of the pro‐inflammatory interleukin‐18 were found hypermethylated.

Conclusions: Children with CD showed a characteristic methylation profile during the first 18 months of life. Compared to non‐CD controls, this modification involved in both metabolic and inflammatory processes seems to be implicated before and at disease onset. The future investigation of DNA methylation, combined with RNASeq, in a larger cohort of matched cases and controls will provide better insights into the underlying mechanisms of CD.

Contact e‐mail address: c.ingenito@ebris.eu

METABOLOMICS ANALYSIS OF FAECAL SAMPLES FROM CHILDREN WITH COELIAC DISEASE AT DIAGNOSIS AND DURING TREATMENT WITH A GLUTEN FREE DIET

Patricia Kelly¹, Gillian Farrell¹, Richard Russell², Richard Hansen³, Paraic Mcgrogan⁴, Christine Edwards⁵, Konstantinos Gerasimidis⁶, Nicholas Rattray¹

¹Strathclyde Institute Of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom, ²Department Of Paediatric Gastroenterology, The Royal Hospital For Children, University of Glasgow, TF, United Kingdom, ³Paediatric Gastroenterology, Hepatology And Nutrition, Royal Hospital for Children, Glasgow, United Kingdom, ⁴Royal Hospital For Sick Children, Yorkhill Operating Division, Paediatric Gastroenterology and Nutrition, TF, United Kingdom, ⁵School Of Medicine, Dentistry & Nursing, University of Glasgow, ER, United Kingdom, ⁶Human Nutrition, School Of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, United Kingdom

Objectives and Study: Recent research has implicated the role of the microbiota in the underlying pathogenesis of coeliac disease (CoD). Studies looking at the functional properties of the gut microbial community are scarce and evidence from such studies can be utilised to further understand disease biology. The present study characterised the faecal metabolome of children with CoD and the effect of treatment with gluten free diet (GFD).

Methods: Using optimised liquid chromatography mass spectrometry (LC‐MS) we profiled the faecal metabolome of 143 participants, aged between 2 and 15 years (mean = 9.2, SD = 3.4), of which 53% were female. This included 27 children at disease diagnosis, 40 during treatment with a GFD, 20 unaffected siblings of treated patients, and 56 healthy controls unrelated to CoD patients.

Results: A panel of 24 CoD specific metabolites were identified, including decreased N‐lauryl‐glycine, xanthine, and piceid, and increased hippuric acid in CoD patients. Pathway enrichment analysis revealed that oxidation of branched chain fatty acids and vitamin B6 metabolism, major metabolic pathways of energy metabolism, were altered in patients. Separation in the global faecal metabolome between untreated and treated patients was also observed, with 57 significant differential metabolites. In patients on a GFD, levels of proline, 2‐aminobutyric acid, and norepinephrine were increased. Enrichment analysis highlighted alanine and glutathione metabolism pathways to be affected in patients on a GFD.

Conclusions: We identified faecal metabolites that have the potential to distinguish patients from healthy controls. Importantly, we identified a metabolic signature that is specific to CoD, irrespective of treatment with a GFD. This could facilitate a deeper understanding of disease aetiology and treatment mechanisms, which may help improve patient outcomes through earlier diagnoses, improved disease monitoring, and prediction of disease outcomes.

Contact e‐mail address: patricia.kelly.2017@uni.strath.ac.uk

USE OF SIMULATION MODEL INCLUDING MULTIPLE VARIABLES TO ESTIMATE THE OPTIMAL SCREENING STRATEGY FOR CELIAC DISEASE IN CHILDHOOD

Jani Mäkinen^1,2, Paula Heikkilä^2,3, Juha Pajula⁴, Khaoula El Mekkaoui^5,6, Ketil Stordal^7,8, Katri Lindfors¹, Jutta Laiho⁹, Jukka Ranta⁵, Jyri Rökman⁵, Heikki Hyöty⁹, Kalle Kurppa^1,2,10,11, Laura Kivelä^1,7,10,12, And The Hedimed Investigator Group⁹

¹Celiac Disease Research Center, Tampere University, Tampere, Finland, ²Center For Child, Adolescent And Maternal Health Research, Tampere University, Tampere, Finland, ³Division Of Oncology, Surgery And Gastroenterology, Tampere University Hospital, Tampere, Finland, ⁴VTT Technical Research Centre of Finland Ltd., Tampere, Finland, ⁵VTT Technical Research Centre of Finland Ltd., Espoo, Finland, ⁶Department Of Computer Science, Aalto University, Espoo, Finland, ⁷Department Of Pediatric Research, Faculty of Medicine, Oslo, Norway, ⁸Division Of Paediatric And Adolescent Medicine, Oslo University Hospital ‐ Rikshospitalet, Oslo, Norway, ⁹Faculty Of Medicine And Health Technology, Tampere University, Tampere, Finland, ¹⁰Department Of Paediatrics, Tampere University Hospital, Tampere, Finland, ¹¹The University Consortium of Seinäjoki, Seinäjoki, Finland, ¹²Children's Hospital And Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Objectives and Study: Celiac disease affects 1‐3% of the population, but most patients remain undiagnosed. Active screening could improve clinical prevalence, but health benefits and cost‐effectiveness of screening are modified by several factors. We assessed optimal screening strategy by utilizing a refined simulation model which combines these various aspects.

Methods: The most cost‐effective screening strategy was evaluated by simulating a probabilistic Markov model with a lifetime horizon. In depth, no‐screening scenario was compared with 272 unique strategies to derive the incremental cost‐effectiveness ratio. Strategies included serological testing at different ages (3‐18 years), single time vs. repeated testing, and genetic testing used to narrow the at‐risk population vs. no genetic testing. Additional adopted assumptions included probabilities to be genetically predisposed to celiac disease, develop celiac disease and symptoms, clinical prevalence in routine practice, treatment success, quality of life, mortality, and annual costs (Table). The required background data was gathered primarily from Sweden, where several population‐based screening studies have been executed.

Results: Untargeted serological testing at a single age point was reportedly more cost‐effective screening strategy than repeated screening or combined use of genetic testing. The cost‐effectiveness of single‐time screening improved with age up to 12 years, after which it remained stable. For repeated screening, the best effectiveness was achieved by untargeted serological testing between the ages of 6‐8 and 16‐18 years. The adopted assumptions had a major effect on the results. The model could be used to point out the most significant lack of data and uncertainty in the field, especially among quality of life and complications.

Conclusions: The most cost‐effective population screening strategy for celiac disease is single‐time untargeted serological screening. Uncertainties in the results reflect the lack of sufficient evidence and need for further studies.

Contact e‐mail address: laura.kivela@tuni.fi

LOCATION OF HISTOPATHOLOGICAL CHANGES IN DIAGNOSTIC BIOPSIES FOR PAEDIATRIC COELIAC DISEASE

Elizabeth Morrisroe¹, David Wood², Francesca Townsend², Andrew fa*gbemi², Loveday Jago², Maureen Lawson², Adnaan Kala², Chai Lee², Virginia Chatzidaki², Sian Copley²

¹Paediatric Gastroenterology, Royal Manchester Children's Hospital, Manchester, United Kingdom, ²Royal Manchester Children's Hospital, Manchester, United Kingdom

Objectives and Study: To retrospectively analyse the location of diagnostic biopsies taken for coeliac disease, specifically comparing the first and second parts of the duodenum (D1 and D2 respectively) within a single tertiary paediatric centre in The United Kingdom.

Methods: Children with complete histology records were identified retrospectively from the departmental coeliac disease database diagnosed on biopsy between 2015 – 2022. Those diagnosed in other centres or without complete histology reports including specification of location of duodenal biopsy were excluded. Data was collected from patient records on gender, age at diagnosis, co‐morbidities, TTG and EMA results and diagnostic biopsy reports. This data was then analysed with particular focus on which area of the duodenum diagnostic histopathological changes were seen.

Results: 73 patients were identified: 29 male, 44 female; mean age at diagnosis was 9 years old (range 1 to 16 years). 72/73 patients had diagnostic changes in D1 (98%) and 47 (64%) in D2. 46/73 (63%) had changes in both D1 and D2. 26/73 (36%) had changes in D1 only and 1/73 (1%) had changes in D2 only. Mean TTG at diagnosis in those with solitary changes to D1 was 70 compared with a mean of 153 in those with changes to both D1 and D2.

Conclusions: The vast majority of patients in this study had diagnostic changes in the proximal duodenum, with over a third having changes only in the proximal and not in the distal duodenum. Solitary changes in D1 were noted particularly with lower levels of TTG upon diagnosis. This data suggests that a change in practice, to routinely collect more samples from the proximal duodenum than is currently suggested by the European Society of Paediatric Gastroenterology Hepatology and Nutrition guidelines, may be indicated in order to increase likelihood of obtaining diagnostic samples during endoscopy.

Contact e‐mail address:

IL4 DOWNREGULATES GLUTEN‐INDUCED INFLAMMATION IN GUT MUCOSA OF CELIAC DISEASE PATIENTS: NEW THERAPEUTIC PERSPECTIVE FOR CELIAC DISEASE

Ilaria Mottola¹, Serena Vitale¹, Stefania Picascia¹, Mariantonia Maglio², Laura Passerini³, Silvia Gregori³, Renata Auricchio², Riccardo Troncone², Carmen Gianfrani¹

¹Biomedicine, Institute of Biochemistry and Cell Biology ‐ CNR, Naples, Italy, ²Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ³Irccs San Raffaele Scientific Institute, 3Raffaele Telethon Institute for Gene Therapy (SR‐Tiget), Milan, Italy

Objectives and Study: Two main forms occur in childhood celiac disease (CD): acute‐CD, characterized by positive anti‐tissue transglutaminase‐tTG antibodies and presence of intestinal villous atrophy, and potential‐CD characterized by positive anti‐tTG but normal mucosa architecture. Recently, we observed a previously unexplored expansion of IL4‐producing T cells in the gut biopsies of children with potential‐CD that inversely correlated with the anti‐tTG antibody titers and histological scores of mucosal damage, being their frequency very low in villous atrophic mucosa (1‐2). In this follow‐up study, we investigated the regulatory function of IL4 in preventing the inflammatory response to gluten in celiac small gut.

Methods: Short‐term T‐cell lines (TCLs) were generated from gut biopsies of children with acute‐ and potential‐CD by cyclic stimulation of intestinal cells with gliadin and growth factors, in absence or presence of exogenous IL4 (control‐TCLs and IL4‐TCLs, respectively). Changes in cytokine production profile, cell infiltrates and gliadin responsiveness induced by IL4 were evaluated at different time points.

Results: IL‐4 treatment induced a significant reduction of IFN‐γ release in culture supernatants collected up to 6 weeks, whereas IL10 production was markedly increased. An increased expansion of CD4+ T‐helper cells, and a decrease of CD8+ T cells and TCRγ/δ+ T cells was also observed in IL4‐TCL compared to control‐TCLs. IFN‐γproduction in response to gliadin and immunogenic peptides was downregulated in IL4‐TCLs compared to control cultures.

Conclusions: Conclusions. Our study demonstrated a hitherto unexplored immunoregulatory function of IL4 on gluten‐induced inflammation in gut mucosa of CD patients. Studies aimed to dissect the role of IL4 in preventing villous atrophy in CD‐predisposed individuals are ongoing. Vitale S. et al. Eur J Immunol. 2019. Vitale S. et al. Pharmaceutics. 2021.

Contact e‐mail address: ilaria.mottola@ibbc.cnr.it

ACROSS THE GLOBE: INSIGHTS INTO DIAGNOSTIC DELAYS IN CHILDREN WITH COELIAC DISEASE

Petra Rižnik¹, Parnia Abrishamchian^2,3, Henedina Antunes⁴, Nevzat Aykut Bayrak⁵, Amir Ben Tov⁶, Joanna Bierła⁷, Nada Boutrid⁸, Ayşegül Bükülmez⁹, Denis Chang^10,11, Maria Luz Cilleruelo¹², Paula Crespo‐Escobar^13,14, Andrew Day^15,16, Veselinka Djurišić¹⁷, Ester Donat¹⁸, Natasa Dragutinovic¹⁹, Marisa Gallant Stahl²⁰, Svetlana Geller²¹, Peter Gillett²², Gieneke Gonera²³, Natalia Gromnatska²⁴, Urszula Grzybowska‐Chlebowczyk^25,26, Anat Guz Mark²⁷, Judit Gyimesi²⁸, Almuthe Christina Hauer²⁹, Angharad Hurley¹⁶, Fatma Iknur Varol³⁰, Tina Kamhi³¹, Michal Kori^32,33, Ilma Korponay‐Szabo^28,34, Sara Lega³⁵, Maureen Leonard³⁶, Edwin Liu³⁷, Catherine Logan Raber³⁸, Eva Martinez³⁹, Mario Masic⁴⁰, Sasha Mealing⁴¹, Carolijn Meijer⁴², Zrinjka Mišak⁴⁰, Caterina Mosca⁴³, Alexandra Papadopoulou⁴⁴, Alina Popp^45,46, Tatiana Raba⁴⁷, Niya Rasheva⁴⁸, Firas Rinawi⁴⁹, Elshathly Saeed⁵⁰, Yasin Sahin⁵¹, Olof Sandström⁵², Naire Sansotta⁵³, Natalia Shapovalova⁵⁴, Anna Szaflarska‐Popławska⁵⁵, Peter Szitányi⁵⁶, Ulas Emre Akbulut⁵⁷, Vaidotas Urbonas⁵⁸, Francesco Valitutti⁵⁹, Margreet Wessels⁶⁰, Jernej Dolinsek^1,61, Mala Setty⁶²

¹Department Of Pediatrics, Gastroenterology, Hepatology And Nutrition Unit, University Medical Center Maribor, Maribor, Slovenia, ²Stanford Medicine Children's Health Center For Ibd And Celiac Disease, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Stanford, United States of America, ³Stanford University School of Medicine, Stanford, United States of America, ⁴Gastroenterology, Hepatology And Nutrition Pediatric Unit And Clinic Academic Center, Hospital de Braga, Braga, Portugal, ⁵Pediatric Gastroenterology, Zeynep Kamil Women and Childrens Training and Research Hospital, University Health sciences, IstanbuL, Turkey, ⁶Pediatric Gastroenterology Institute, "Dana‐Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Affiliated to the Tel Aviv University Faculty of Medicine, Tel Aviv, Israel, Tel Aviv, Israel, ⁷Department Of Pathom*orphology, The Children's Memorial Health Institute, Warsaw, Poland, ⁸Pediatric Department, Mother & Child University Hospital El Eulma, University of Setif 1, Setif, Algeria, ⁹Pediatric Gastroenterology, Afyonkarahisar Health Sciences University Faculty of Medicine, Afyonkarahisar, Turkey, ¹⁰Harvard Medical School, Boston, United States of America, ¹¹Division Of Gastroenterology And Nutrition, Boston Children's Hospital, Boston, United States of America, ¹²Pediatric Gastroenterology Unit. Puerta de Hierro Majadahonda Hospital, Madrid, Spain, ¹³ADViSE Research Group. Department of Health Science, European University Miguel de Cervantes, Valladolid, Spain, ¹⁴Nutrition and Obesity Unit. Hospital Recoletas Campo Grande, Valladolid, Spain, ¹⁵Paediatric Gastroenterology, Christchurch Hospital, Christchurch, New Zealand, ¹⁶Department Of Paediatrics, University of Otago, Christchurch, New Zealand, ¹⁷Clinical Centre of Montenegro, Institute for Children's Disease, Podgorica, Montenegro, ¹⁸Pediatric Gastroenterology And Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain, ¹⁹Department Of Gastroenterology, University Children's Hospital, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, ²⁰Colorado Center For Celiac Disease, University of Colorado School of Medicine, Children's Hospital Colorado, Denver, CO, United States of America, ²¹Gastroenterology, Republican Specialized Scientifical Practical Medical Center of Pediatrics, Tashkent, Uzbekistan, ²²Gi Department, Royal Hospital For Children and Young People (RHCYP), Edinburgh, United Kingdom, ²³Wilhelmina Ziekenhuis Assen, Assen, Netherlands, ²⁴Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, ²⁵Department Of Pediatrics, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Katowice, Poland, ²⁶Faculty Of Medical Science In Katowice, Medical University of Silesia, Katowice, Poland, ²⁷Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel, ²⁸Coeliac Centre, Heim Pál National Paediatric Institute, Budapest, Hungary, ²⁹Medical University of Graz, Graz, Austria, ³⁰Pediatric Gastroenterology, Inonu University, Faculty of Medicine, Malatya, Turkey, ³¹Department Of Gastroenterology, Hepatology And Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia, ³²Kaplan Medical Center, Pasternak St., Israel, ³³Faculty Of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ³⁴Paediatrics, University Of Debrecen, Debrecen, Hungary, ³⁵Gastroenterology, Digestive Endoscopy And Nutrition Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy, ³⁶Center For Celiac Research And Treatment, Mass General Hospital for Children and Division of Pediatric Gastroenterology, Harvard Medical School, Boston‐Massachusetts, United States of America, ³⁷Colorado Center For Celiac Disease, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, United States of America, ³⁸Children's National Hospital, Washington, United States of America, ³⁹Department Of Pediatric Gastroenterology And Nutrition, La Paz University Hospital, Madrid, Spain, ⁴⁰Referral Center For Pediatric Gastroenterology And Nutrition, Children's Hospital Zagreb, Zagreb, Croatia, ⁴¹Gastroenterology, Hepatology And Liver Transplant Unit, Children's Health Queensland Hospital and Health Service, Queensland Children's Hospital, South Brisbane, Australia, ⁴²Department Of Pediatric Gastroenterology, Leiden University Medical Centre, Willem Alexander Children's Hospital, Leiden, Netherlands, ⁴³Department Of Translation Medical Science And European Laboratory For The Investigation Of Food Induced Disease (elfid), University of Naples Federico II, Naples, Italy, ⁴⁴Division Of Gastroenterology And Hepatology, First Department Of Pediatrics, University Of Athens, Children's Hospital Agia Sofia, Athens, Greece, ⁴⁵National Institute for Mother and Child Health "Alessandrescu‐Rusescu", Bucharest, Romania, ⁴⁶Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, ⁴⁷Department Of Pediatrics, "Nicolae Testemitanu" State University of Medicine and Pharmacy, Chisinau, Moldova, ⁴⁸Department Of Pediatrics, Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria, ⁴⁹Pediatric Gastroenterology Unit, Emek medical center & The Ruth and Bruce Rappaport Faculty of Medicine, Afula, Israel, ⁵⁰Prince Abdullah Bin Khalid Coeliac Disease Research, Faculty of medicine, Department of pediatrics college of medicine King Saud University, Riyadh, Saudi Arabia, ⁵¹Division of Pediatric Gastroenterology, Gaziantep Islam Science and Technology University Medical Faculty, Gaziantep, Turkey, ⁵²Department Of Pediatrics, Department of Clinical Sciences, Umeå, Sweden, ⁵³Paediatric Hepatology Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy, Bergamo, Italy, ⁵⁴Saint Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation, ⁵⁵Department Of Paediatric Endoscopy And Gastrointestinal Function Testing, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland, ⁵⁶Dept. Of Paediatrics And Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic, ⁵⁷Pediatric Gastroenterology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey, ⁵⁸Clinic of Children's Diseases of Vilnius University Faculty of Medicine, Vilnius,, Lithuania, ⁵⁹Pediatric Clinic, Department Of Surgical And Biomedical Sciences, University of Perugia, Perugia, Italy, ⁶⁰Department Of Pediatrics, Rijnstate Hospital, Arnhem, Netherlands, ⁶¹Department Of Pediatrics, University of Maribor, Faculty of Medicine, Maribor, Slovenia, ⁶²Co‐director, Pediatric Gastroenterology, Hepatology And Nutrition, University of California San Francisco (UCSF), Benioff Children's Hospital Oakland, San Francisco, United States of America

Objectives and Study: Numerous studies conducted globally have consistently identified prolonged diagnostic delays in coeliac disease (CD). The primary objective of our study was to assess the extent of diagnostic delays in children newly diagnosed with CD, in different countries worldwide.

Methods: A retrospective multi‐center study of the ESPGHAN Celiac Disease Special Interest Group project CD in Focus involved pediatric gastroenterologists from 29 countries (Europe, North America, Asia, North Africa, Australasia). Medical data from children (<19y) diagnosed since 2021 was analyzed. Focus of the study were the delays from the first symptom to final diagnosis. We compared diagnostic delays between countries from the Danube region participating in the EU CD SKILLS awarenes rising project and the others.

Results: The study included data from 1466 symptomatic children newly diagnosed with CD (64.5% female; median age 7.5y). Median diagnostic delay was 7m (range 0m – 15.5y). Significant differences in diagnostic delays were noted among countries (p<0.001), with Russia and Uzbekistan having the longest delays (32m and 22m) and Hungary, Turkey, and New Zealand (all 5m) and Italy (4m) the shortest. No significant differences were found between countries from the Danube region and the others (7m vs 8m; p=0.54). Worldwide, longer delays were found in children without malabsorption (abdominal pain 8m, constipation 11m) compared to those with diarrhoea (6m). Children with dermatitis herpetiformis experienced the longest delays (15m), while those with fatty stools the shortest (3m; p<0.001).

Conclusions: Important diagnostic delays in CD are observed globally, especially when malabsorptive features are missing or CD presents with constipation. Significant delays can be seen when diagnosing children with abdominal pain, the most prevalent symptom in children. These results emphasize a necessity for increased awareness of healthcare professionals and further education to expedite the identification of CD with its diverse manifestations, indicating also the need for global harmonisation of CD management practices.

Contact e‐mail address: petra.riznik@gmail.com

MICROBIAL TRANSGLUTAMINASE MAY PLAY A ROLE IN CELIAC DISEASE BY INCREASING EPITHELIAL UPTAKE OF GLIADIN PEPTIDES

Sebastian Stricker¹, Jan De Laffolie¹, Klaus‐Peter Zimmer¹, Silvia Rudloff^1,2

¹Department of General Pediatrics & Neonatology, Justus‐Liebig‐University, Giessen, Germany, ²Institute of Nutritional Sciences, Justus‐Liebig‐University, Giessen, Germany

Objectives and Study: Transglutaminase 2 (TG2) mediated deamidation of gliadin peptides plays a critical role in the pathogenesis of celiac disease (CD). TG2 is expressed by intestinal epithelial cells and plays a role in the transport of gliadin peptides within enterocytes. In addition to TG2, microbial transglutaminase (mTG) might be involved in the pathogenesis of CD. mTG is used as a technical additive in food production und may also be released by certain bacteria within the intestinal microbiota. In contrast to other transglutaminases, mTG modifies gliadin peptides in the same way as TG2. In this study, we aimed to investigate the affinity of mTG and TG2 to gliadin peptides and the influence of both transglutaminases on the epithelial uptake of gliadin peptides.

Methods: Crosslinking affinity of TG2 and mTG to different biotinylated gliadin peptides (P56‐88, P31‐49) was investigated using a photometric assay. The influence of mTG and TG2 on the epithelial transport of fluorochrome‐ and biotin‐conjugated gliadin peptides by the gastrointestinal epithelial cell line Caco‐2 was investigated using fluorometry and immunofluorescence microscopy.

Results: Crosslinking affinity of mTG to gliadin peptides was up to 10‐fold higher in comparison to TG2. The uptake of fluorochrome‐conjugated gliadin peptides P56‐88 and P31‐43 by Caco‐2 cells was significantly increased by coincubation with mTG compared to TG2 (368 ± 47 % and 222 ± 15 %, respectively; p < 0.0001). mTG treatment also resulted in a significantly higher uptake of biotinylated gliadin peptides compared to TG2. Finally, all effects observed were significantly reduced by using transglutaminase inhibitors (mTG blocker and the TG2 inhibitor ERW1041).

Conclusions: mTG showed a higher affinity to gliadin peptides compared to TG2. Further, mTG significantly increased the intestinal uptake of gliadin peptides at nanomolar concentrations. These data suggest a potential detrimental role of mTG in the context of CD.

Contact e‐mail address: Sebastian.Stricker@paediat.med.uni‐giessen.de

EARLY CHILDHOOD INTAKE OF SELECTED MICRONUTRIENTS AND RISK OF COELIAC AUTOIMMUNITY AND COELIAC DISEASE: THE TEDDY STUDY

Jimin Yang¹, Lazarus Mramba¹, Elin Hård Af Segerstad², Sibylle Koletzko^3,4, Kalle Kurppa⁵, Katri Lindfors⁶, Ulla Uusitalo¹, Carin Andrén Aronsson⁷, William Hagopian⁸, Marian Rewers⁸, Richard Mcindoe⁹, Jorma Toppari¹⁰, Anette‐G Ziegler¹¹, Beena Akolkar¹², Jeffrey Krischer¹, Edwin Liu¹³, Jill Norris⁸, Suvi Virtanen¹⁴, Daniel Agardh⁷

¹Health Informatics Institute, University of South Florida, Tampa, FL, United States of America, ²Pediatric Research Institute, Oslo University Hospital And Celiac Disease And Diabetes Unit, Clinical Sciences, Lund University, Malmo, Sweden, ³Department Of Pediatrics, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany, Munich, Germany, ⁴Department Of Pediatrics, Gastroenterology And Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland, ⁵Tampere University and Tampere University Hospital, Tampere, Finland, ⁶Tampere University, Tampere, Finland, ⁷Lund University, Malmo, Sweden, ⁸University of Colorado, Aurora, CO, United States of America, ⁹Augusta University, Augusta, GA, United States of America, ¹⁰University of Turku and Turku University Hospital, Turku, Finland, ¹¹Technische Universität München, and Forschergruppe Diabetes e.V, Neuherberg, Germany, ¹²National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, United States of America, ¹³Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, United States of America, ¹⁴Finnish Institute for Health and Welfare and Tampere University and Tampere University Hospital, Tampere, Finland

Objectives and Study: This study investigated whether the intake of vitamins and minerals related to immune function was associated with the risk of coeliac disease autoimmunity (CDA) and coeliac disease (CD).

Methods: Genetically at‐risk children (n=7,008) followed for at least 13 years in The Environmental Determinants of Diabetes in The Young (TEDDY) study were screened for tissue transglutaminase autoantibodies (tTGA) and development of CD. CDA was defined as being tTGA positive in two samples collected 3 months apart. CD was diagnosed if Marsh score >1 in small bowel biopsies or mean tTGA level ≥100 U/mL in two consecutive samples. Repeated 3‐day food records (quarterly and semi‐annually) were used to estimate nutrient intake. Nutrient intake per 1000kcal was used in time‐dependent Cox proportional hazard models adjusted for country, HLA genotype, sex, CD family history, energy intake, gluten exposure, and use of probiotics supplements.

Results: CDA was confirmed in 1,340 participants, 465 (35%) of whom were later diagnosed with CD. CDA was associated with higher intake of vitamin D (from foods and supplements) from birth to age 2 years (hazard ratio (HR) 1.08, 95% CI 1.01, 1.14, p=0.018), to age 3 years (HR 1.12, 95% CI 1.05, 1.20 p=0.004), to age 4 years (HR 1.16, 95% CI 1.09, 1.23, p<0.001), and to age 5 years (HR 1.17, 95% CI 1.10, 1.24, p<0.001). Positive associations were also observed between the risk of CDA and iron intake, and between the risk of CD with the intake of both nutrients.(Figure 1). The intake of vitamins (A, C, E, K, B6, B12, folate), selenium, copper, and zinc were not associated with the risk of CDA or CD.

Conclusions: Higher vitamin D and iron intake during early childhood may contribute to both the risk of CDA and CD in children with increased genetic risk.

Contact e‐mail address: jimin.yang@epi.usf.edu

MULTICENTRIC CROSS SECTIONAL STUDY OF QUALITY OF LIFE IN CHILDREN WITH CHRONIC PANCREATITIS

Ankit Agrawal¹, Anshu Srivastava¹, Prabhakar Mishra², Rohan Malik³, Vivek Agrawal⁴, Akhil Raj⁵, Moinak Sarma¹, Ujjal Poddar¹, Nowneet Bhat⁵

¹Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, ²Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, ³Pediatric Gastroenterology, All India Institute of Medical Sciences, DELHI, India, ⁴Psychiatry, King George Medical University, Lucknow, India, ⁵Pediatric Gastroenterology, All India Institute of Medical Sciences, RISHIKESH, India

Objectives and Study: The impact of chronic pancreatitis (CP) on quality of life (QOL) in children is not well established. Our primary objective was to evaluate the QOL,identify contributing factors, and determine the prevalence of anxiety and depression in children with CP.

Methods: Children (8‐18y old) with CP were prospectively enrolled across three pediatric gastroenterology centres in India. QOL was assessed using pediatric QOL inventory (PedsQL 4.0) scale, administered to both children and their parents. Anxiety and depression prevalence were studied using the Revised Children's Anxiety and Depression Scale (RCADS 25). Univariate and multivariable analysis was done.Comparison was done with published QOL data in healthy Indian children

Results: 121 children with CP (boys‐57.9%,age at diagnosis 11.6±3.8 years,age at QOL 14±3.2years) were enrolled. Majority (82.7%) had pain and advanced disease (Cambridge grade IV‐ 63.6%). Children with CP had poorer QOL compared to controls (total score 74.6±16 vs. 87.5±11.1,p<0.0001).Older children were similar to younger ones, except for a poorer emotional QOL.Taking QOL <‐2SD of controls, ~35% had poor physical (50.9±11.9) and 20% had poor psychosocial (PS)QOL (52.1±7.2).On univariable analysis presence of pain,advanced disease, and lower socioeconomic status (SES) were significantly affected physical QOL;however in PS QOL only pain was significant. On multivariable analysis, presence of pain and lower SES adversely affected both physical (no pain; regression(β) 24.4, 95%CI: 11.6‐37.2, upper SES; (β) 9.9, 95%CI: 2.9‐16.8, p<0.05) and PS QOL (no pain; (β) 17, 95%CI: 6.9‐27, upper SES; (β) 5.5, 95%CI: 0.08‐11, p<0.05). Continuous pain was worse than episodic pain than no pain (84.1±18.0 vs 73.9±19.2 vs 59.6±21.5). Additionally, girls had poor PS health than boys (odds ratio (OR) 3.1, 95%CI:1.23‐7.31). Anxiety and depression were uncommon (2,1.6%).QOL scores were similar across centres.

Conclusions: Patient with CP had impaired QOL, both in physical and PS domain. Presence of pain and lower SES adversely affected QOL. Psychiatric comorbidities were uncommon.

Contact e‐mail address: avanianshu@yahoo.com

EXPANDING THE INDICATIONS FOR CFTR MODULATOR DRUGS IN CYSTIC FIBROSIS UTILIZING INTESTINAL ORGANOIDS

Naama Sznadjer¹, Shira Leebhoff¹, Deborah Duran¹, Widad Samman¹, Elinor Haimov², Aielet Stolovas³, Malena Cohen‐Cymberknoh³, Oded Breuer³, Michal Shteinberg⁴, Dario Prais^5,6, Michal Gur⁷, Michael Wilschanski², Myriam Grunewald^1,8, Liron Birimberg‐Schwartz^1,2

¹Hadassah Organoid Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ²Pediatric Gastroenterology, Hadassah Hebrew University Medical Center, JERUSALEM, Israel, ³Pediatric Pulmonary Unit And Cystic Fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ⁴Cystic Fibrosis Center, Carmel Medical Center, The Ruth And Bruce Rappaport Faculty Of Medicine, Technion Israel Institute of Technology, Haifa, Israel, ⁵Kathy And Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel,, Petach Tikva, Israel, ⁶Faculty Of Medicine, Tel Aviv University, Tel Aviv, Israel, ⁷Pediatric Pulmonary Institute, Ruth Rappaport Children's Hospital, Rambam Medical Center, Haifa, Israel, ⁸Department Of Developmental Biology And Cancer Research, Faculty Of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

Objectives and Study: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionized the management of cystic fibrosis (CF), markedly improving disease outcomes. However, certain CFTR mutations remain underexplored due to their scarcity, impeding conventional clinical trials. This study aims to investigate the in‐vitro response of CFTR mutations not currently approved for CFTR modulator therapy, utilizing patient‐derived intestinal organoids.

Methods: Intestinal organoids were generated from rectal biopsies of CF patients with CFTR mutations not currently approved for CFTR modulator therapy, along with non‐CF controls. To establish CFTR baseline function, a Dimethyl sulfoxide control was employed. The responsiveness of organoids to CFTR modulators VX‐770 (ivacaftor), VX‐661+ VX‐770 (tezacaftor/ivacaftor), and VX‐445 + VX‐661 + VX‐770 (elexacaftor/tezacaftor/ivacaftor) was also evaluated. Response was quantified by calculating the increase of the total organoid area under the curve (AUC) over 60‐minutes following forskolin (Fsk) stimulation, employing the Fsk‐ induced swelling (FIS) assay.

Results: Baseline CFTR function, measured as the AUC at 0.8 µM Fsk, averaged at 1342 (Standard Deviation [SD] ± 192) for the 7 non‐CF controls compared to 138 (SD ± 143) for the CF samples. Six of the 8 CF patients exhibited an in‐vitro response to modulators. Of these, 5 patients demonstrated significant response to VX‐445 + VX‐661 + VX‐770 and carried the mutations N1303K/N1303K (2 patients), Q359K/T360K (hom*ozygous, 2 patients), N1303K/G542X. One patient with G542X/R334W mutations responded most favorably to VX‐770, while two patients showed no significant response to any tested modulators [2183AA‐‐>G/2183AA‐‐>G, 2043delG/2043delG]. These results facilitated drug approval for the 6 patients with in‐vitro response, and ongoing data collection is assessing their clinical response.

Conclusions: Our study reveals the in‐vitro responsiveness of CFTR mutations not approved for treatment to CFTR modulators, as evidenced by the validated FIS assay. Intestinal organoids are an efficient tool, expanding the indications for CFTR modulators and facilitating personalized medicine for CF patients.

Contact e‐mail address: lbschwartz@hadassah.org.il

IMPACT OF ELEVATED SERUM TRIGLYCERIDES ON CHILDREN WITH ACUTE RECURRENT OR CHRONIC PANCREATITIS FROM INSPPIRE‐2

Matthew Giefer¹, Zachary M Sellers², Fuchenchu Wang³, Gretchen Cress⁴, Maisam Abu‐El‐Haija⁵, Ankur Chugh⁶, Reuven Zev Cohen⁷, Elissa Downs⁸, Douglas Fishman⁹, Jay Freeman¹⁰, Cheryl Gariepy¹¹, Tanja Gonska¹², Amit Grover¹³, Douglas Lindblad¹⁴, Quin Liu¹⁵, Asim Maqbool¹⁶, Jacob Mark¹⁷, Brian Mcferron¹⁸, Megha Mehta¹⁹, Veronique Morinville²⁰, Kenneth Ng²¹, Robert Noel²², Chee Y Ooi²³, Emily Perito²⁴, Madhura Phadke²⁵, Wenly Ruan²⁶, Sarah Jane Schwarzenberg²⁷, David Troendle²⁸, Michael Wilschanski²⁹, Yuhua Zheng³⁰, Ying Yuan³¹, Mark Lowe³², Aliye Uc⁴

¹The University of Queensland and Ochsner Hospital for Children, New Orleans, United States of America, ²Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stanford University, Palo Alto, United States of America, ³University of Texas MD Anderson Cancer Center, Houston, United States of America, ⁴University of Iowa, Iowa City, United States of America, ⁵Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, United States of America, ⁶Medical College of Wisconsin/Children's Wisconsin, Milwaukee, United States of America, ⁷Children's Healthcare of Atlanta and Emory University, Atlanta, United States of America, ⁸University of Minnesota Masonic Children's Hospital, Minneapolis, United States of America, ⁹Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine and Texas Children's Hospital, Houston, United States of America, ¹⁰The Ohio State University, Columbus, United States of America, ¹¹Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, United States of America, ¹²Department of Pediatrics, University of Toronto and Research Institute, Hospital for Sick Children, Toronto, Canada, ¹³Boston Children's Hospital and Harvard Medical School, Boston, United States of America, ¹⁴Children's Hospital of Pittsburgh/UPMC, Pittsburgh, United States of America, ¹⁵Cedars‐Sinai Medical Center, Los Angeles, United States of America, ¹⁶Children's Hospital of Philadelphia, Philadelphia, United States of America, ¹⁷Children's Hospital of Colorado, Aurora, United States of America, ¹⁸Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, United States of America, ¹⁹University of Texas Southwestern Medical School, Dallas, United States of America, ²⁰Montreal Children's Hospital, McGill University, Montreal, Canada, ²¹John Hopkins Children's Center, Johns Hopkins University School of Medicine,, Baltimore, United States of America, ²²Baylor College of Medicine, San Antonio, United States of America, ²³Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales, Sydney Children's Hospital Randwick, Sydney, Australia, ²⁴University of California San Francisco, San Francisco, United States of America, ²⁵University of Pittsburgh, Pittsburgh, United States of America, ²⁶9. Baylor College of Medicine and Texas Children's Hospital, Houston, United States of America, ²⁷University of Minnesota, Minneapolis, United States of America, ²⁸UT Southwestern Medical Center, Dallas, United States of America, ²⁹Pediatric Gastroenterology, Hadassah Hebrew University Medical Center, JERUSALEM, Israel, ³⁰Children's Hospital Los Angeles, Los Angeles, United States of America, ³¹University of TexasMD Anderson Cancer Center, Houston, United States of America, ³²The Washington University School of Medicine, St Louis, United States of America

Objectives and Study: In adults, mild‐moderate hypertriglyceridemia (HTG), not just severe HTG, increases acute and chronic pancreatitis risk (AP and CP respectively). In children, severe HTG increases AP risk, but it is not known if mild‐moderate HTG also increases risk of AP and/or development of CP. To determine if varying levels of triglyceride (TG) elevation are associated with increased CP development and/or pancreatitis‐associated complications in children with acute recurrent panceratitis (ARP) or CP.

Methods: Design, setting, and participants: Longitudinal data from the INSPPIRE‐2 (INternational Study group of Pediatric Pancreatitis: In search for a cuRE‐2) cohort of children with ARP or CP (n=559) were analyzed. Subjects were divided into normal TG (<150 mg/dL or 1.7 mmol/L), any HTG (>150 mg/dL or >1.7 mmol/L), mild‐moderate HTG (150‐499 mg/dL or 1.7‐5.6 mmol/L), moderate HTG (500‐999 mg/dL or 5.6‐11.3 mmol/L), and severe HTG groups (>1,000 mg/dL or >11.3 mmol/L) based on each subject's highest serum TG value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed. Exposures: Plasma levels of fasting TG. Main outcomes and measures: Proportion of cohorts with CP and pancreatitis‐associated complications, number of pancreatitis events.

Results: In children with ARP or CP, HTG was not associated with more frequent pancreatitis attacks, nor increased progression to CP. However, HTG severity was associated with increased pancreatic inflammation, exocrine pancreatic insufficiency, pancreatic cysts, pain, hospital days/number of hospitalizations, and intensive care.

Conclusions: HTG increases AP severity, pancreatitis complications and disease burden among children with ARP or CP. HTG in children who already carry a diagnosis of ARP or CP does not increase pancreatitis episodes. HTG does not increase CP development among children with ARP. Evaluation and treatment of mild‐moderate HTG should be considered to reduce pancreatitis‐associated complications and disease burden.

Contact e‐mail address: Matthew.Giefer@ochsner.org

CORRELATION OF PLASMA TOTAL FATS WITH PLASMA OMEGA‐3 FATS AFTER ORAL CHALLENGE

Kateryna Pierzynowska¹, Stefan Pierzynowski¹, Kamil Zaworski², Robert Gallotto³, Meghana Sathe⁴, Steven Freedman⁵, Drucy Borowitz⁶

¹Department Of Biology, Lund University, Lund, Sweden, ²The Kielanowski Institute Of Animal Physiology And Nutrition, Polish Academy of Sciences, Jablonna, Poland, ³Anagram Therapeutics, Boston, United States of America, ⁴Pediatric Gastroenterology, Hepatology And Nutrition, University of Texas Southwestern/Children's Health, Dallas, United States of America, ⁵Gastroenterology, 1. Beth Israel Deaconess Medical Center, Boston, United States of America, ⁶Pediatrics, Jacobs School of Medicine, University at Buffalo, Buffalo, United States of America

Objectives and Study: Plasma levels of omega‐3 (O3) fats depend on dietary intake with little endogenous production. DHA triglyceride can be used in an omega‐3 substrate absorption challenge test to directly measure fat absorption and lipase activity¹. We hypothesized that there would be a correlation between levels of O3 fats and levels of total dietary fats.

Methods: This work was part of the development of a microbial lipase (ANG003) in the exocrine pancreatic insufficient (EPI) pig model. Five pigs were given a standardized O3 dose along with either ANG003 (80 mg or 120 mg) or pancrelipase 600 mg. Blood was drawn following the O3 substrate challenge and was analyzed for O3 fats (DHA+EPA) and total fatty acid (FA) levels (c14:c24). Statistical analysis used Pearson correlation; differences were considered significant if p ≤ 0.05.

Results: At 2 hours after ingestion there was significant correlation between DHA+EPA and total FA for both the 80 mg and 120 mg ANG003 doses (r=0.894; p=0.041 and r=0.98; p=0.003 respectively) but none was seen for pancrelipase. At 4 hours, there was significant correlation between DHA+EPA and total FA for the 120 mg dose (r=0.907; p=0.034) but not for the ANG003 80 mg dose or for pancrelipase.

Conclusions: We demonstrated that a microbial lipase improves both O3 and total fat absorption in EPI pigs and that levels of DHA+EPA are highly correlated with total fat absorption. Pancrelipase has low efficacy for hydrolysis of DHA and EPA, which may explain the lack of correlation seen. If the oral O3 triglyceride substrate challenge test is validated in humans, it can be a marker of lipolysis of a wide range of fats that could be used in research or clinical settings. 1. doi:10.1371/journal.pone.0284651

Contact e‐mail address: rgallotto@anagramtx.com

THE IMPACT OF CFTR MODULATOR THERAPY ON ACUTE PANCREATITIS FREQUENCY IN CHILDREN WITH ACUTE RECURRENT OR CHRONIC PANCREATITIS: A PRELIMINARY REPORT FROM INSPPIRE‐2

Michael Wilschanski¹, Gila Ginzburg², Jacob Mark³, Ankur Chugh², Feng Tian⁴, Gretchen Cress⁵, Maisam Abu‐El‐Haija⁶, Reuven Zev Cohen⁷, Elissa Downs⁸, Douglas Fishman⁹, Cheryl Gariepy¹⁰, Mathew Giefer¹¹, Tanja Gonska¹², Amit Grover¹³, Douglas Lindblad¹⁴, Quin Liu¹⁵, Asim Maqbool¹⁶, Brian Mcferron¹⁷, Megha Mehta¹⁸, Veronique Morinville¹⁹, Kenneth Ng²⁰, Robert Noel²¹, Chee Y Ooi²², Emily Perito²³, Zachary M Sellers²⁴, Fuchenchu Wang⁴, Ying Yuan⁴, Mark Lowe²⁵, Aliye Uc⁵

¹Pediatric Gastroenterology, Hadassah Hebrew University Medical Center, JERUSALEM, Israel, ²Medical College of Wisconsin/Children's Wisconsin, Milwaukee, United States of America, ³Children's Hospital of Colorado, Aurora, United States of America, ⁴University of Texas MD Anderson Cancer Center, Houston, United States of America, ⁵University of Iowa, Iowa City, United States of America, ⁶Cincinnati Children's Hospital Medical Center, College of Medicine, University of Cincinnati, Cincinnati, United States of America, ⁷Children's Healthcare of Atlanta and Emory University, Atlanta, United States of America, ⁸University of Minnesota Masonic Children's Hospital, Minneapolis, United States of America, ⁹Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine and Texas Children's Hospital, Houston, United States of America, ¹⁰Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, United States of America, ¹¹Ochsner Hospital for Children, The University of Queensland, New Orleans, United States of America, ¹²Department of Pediatrics, University of Toronto and Research Institute, Hospital for Sick Children, Toronto, Canada, ¹³Boston Children's Hospital and Harvard Medical School, Boston, United States of America, ¹⁴Children's Hospital of Pittsburgh/UPMC, Pittsburgh, United States of America, ¹⁵Cedars‐Sinai Medical Center, Los Angeles, United States of America, ¹⁶Children's Hospital of Philadelphia, Philadelphia, United States of America, ¹⁷Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, United States of America, ¹⁸Riley Hospital for Children, IndianaUniversity School of Medicine, Indianapolis, United States of America, ¹⁹Montreal Children's Hospital, McGill University, Montreal, Canada, ²⁰John Hopkins Children's Center, Johns Hopkins University School of Medicine,, Baltimore, United States of America, ²¹Baylor College of Medicine, San Antonio, United States of America, ²²Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales, Sydney Children's Hospital Randwick, Sydney, Australia, ²³University of California San Francisco, San Francisco, United States of America, ²⁴Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stanford University, Palo Alto, United States of America, ²⁵The Washington University School of Medicine, St Louis, United States of America

Objectives and Study: CFTR modulator therapies are small molecules approved for the treatment of CF. They improve exocrine pancreatic function and reduce acute pancreatitis (AP) episodes in CF. The impact of CFTR modulator therapies on children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) carrying CFTR variants has not been investigated.

Methods: This was a multi‐center retrospective cohort study of children with ARP or CP enrolled in the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE‐2 (INSPPIRE‐2). Inclusion criteria were at least one CFTR variant and modulator therapy initiation during the data collection period. The number of AP episodes before and after modulator therapies were compared for all collected data.

Results: Of 1001 eligible INSPPIRE‐2 participants, 22 (10 female) met the inclusion criteria and 16 had at least 1 year follow‐up data after CFTR modulator initiation, 11 (69%) had ARP, and 5 (31%) had CP. The total number of AP episodes was 62 across all 16 subjects (over a 12‐year period) pre‐HEMT, vs 5 in 4 subjects (2 ARP, 2 CP) on modulator therapy (over a 6‐year period),12 had none. Due to the non‐normal distribution of AP episodes over time on HEMT, the incidence density was calculated as the total number of AP episodes per total person time. Pre‐modulator therapy incidence density was 0.305 vs on‐modulator therapy incidence density was 0.185, with a ~40% decrease, which was significant using the Poisson regression with random effect (p < 0.001).

Conclusions: In this preliminary report from the largest cohort of children with ARP or CP, CFTR modulator therapy significantly decreased the number of AP episodes if CFTR variants were present. Long‐term follow‐up will determine if this effect would be sustained and prevent complications associated with ARP or CP. Acknowledgements: This project was funded from the following grants: NIDDK/NCI: U01DK108334 and U01DK108328

Contact e‐mail address: michaelwil@hadassah.org.il

ENDOSCOPIC TREATMENT OF TRACHEOESOPHAGEAL FISTULA CAUSING RECURRENT ASPIRATION PNEUMONIA IN TWO CHILDREN

Alexandra Papadopoulou

Division Of Gastroenterology And Hepatology, First Department Of Pediatrics, University Of Athens, Children's Hospital Agia Sofia, Athens, Greece

Objectives and Study: Tracheoesophageal fistula (TEF) is a congenital malformation that is often combined with esophageal atresia. Surgical treatment is based on surgical ligation, which is sometimes associated with recurrence. The aim of this video is to present the endoscopic treatment of a recurrent TEF in two children.

Methods: A boy aged 2 years and a girl aged 6 years with recurrent aspiration due to chronic recurrent TEF were treated endoscopically. The boy had undergone unsuccessful surgery in another country and was unable to eat on admission due to choking. In both cases, the presence of TEF was confirmed by upper endoscopy and infusion of methylene blue through a tracheal tube (Images 1‐2).

Results: The boy underwent endoscopic cauterization with argon plasma coagulation (ERBE) of the fistula edges through the esophagus (Images 3‐4) and placement of an over‐the‐scope clip (OVESCO, Image 5), followed by cauterization with Bugbee electrodes of the fistula edges through the trachea by the otolaryngologist (Image 6) and injection of Tisseel glue (Image 7). Closure of the fistula was confirmed by an esophagogram (Image 8) and a repeat endoscopy with methylene blue infusion (Image 9). The therapeutic effect lasted only 3 weeks, as the dietary instructions to introduce pureed food during refeeding were not followed and the child, who was living in a refugee camp, was placed on a full diet without restrictions. In the second case, the same procedure was performed (Image 10) but without the use of a clip, with gradual refeeding, initially with pureed food. After 2 years of follow‐up, the child is still asymptomatic, fully nourished and the fistula remains closed.

Conclusions: Endoscopic treatment of TEF is a safe and effective therapeutic approach, provided that dietary instructions are followed after the procedure, and offers important advantages over the conventional surgical approach.

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SUCCESSFUL MANAGEMENT OF AN OESOPHAGEAL PERFORATION VIA ENDOSCOPIC VACUUM (ENDO‐VAC) THERAPY – A CASE REPORT

Dominique Schluckebier¹, Richard Lindley², Elizabeth Gavens², Mike Thomson¹

¹Paediatric Gastroenterology, Sheffield's Children's Hospital, Sheffield, United Kingdom, ²Paediatric Surgery, Sheffield's Children's Hospital, Sheffield, United Kingdom

Objectives and Study: To present a video clip of the successful closure of an oesophageal perforation via endoscopic vacuum (endo‐vac) therapy in an eight‐year old girl.

Methods: Case report An 8‐year old girl was admitted to our intensive care unit for increased work of breathing and a sepsis‐like picture. She was known for dystonic tetraparesis and cerebral palsy related to neonatal hypoxic ischemic encephalopathy. Due to severe reflux disease she required two fundoplicatio in the past and had a gastrostomy and jejunostomy inserted. She was jejunally fed but presented with persistent retching and vomiting for several month and had recently developped coffee ground aspirates from her PEG site. A CT scan reveiled a right lateral distal oesophageal rupture as well as diaphragmatic hernia containing part of the splenic flexure (Figure 1). A thoracic drain was inserted however conservative managmenent failed and the patient remained dependent on invasive ventilation.

Results: Endoscopic vacuum therapy (endo‐vac) was performed (video clip): 1. The perforation was identified via endoscopy. 2. A vacuum sponge attached to an aspiration tube was inserted through the nose and was pulled into the right position with an endoscope which was inserted through the gastrostomy. 3. The correct position was confirmed via fluoroscopy. 4. The suction tube with the VAC sponge was attached to a suction device and remained on continious suction (negative pressure) over the following 5 days. The endo‐vac was retrieved via endoscopy at day 5. No further leakage occured. The patient was succesfully extubated at day 6.

Conclusions: We report the first case of endo‐vac assisted management of an oesophageal perforation in a child in the UK. Similar cases have been described by Manfredi et al in the United States and by Viala et al in Paris. Endo‐vac therapy is an attractive alternative to oesophageal stenting with faster healing and therefore decreased recovery time.

Contact e‐mail address: d.schluckebier@nhs.net

VIDEO PRESENTATION FOR STRETTA

Shishu Sharma, Mike Thomson

Paediatric Gastroenterology, Sheffield's Children's Hospital, Sheffield, United Kingdom

Objectives and Study: We are submitting a short video for the endoscopy clip session to demonstrate the STRETTA procedure in children. The procedure was performed as part of single centre prospective pilot study to assess the feasibiliy and safety of STRETTA procedure in paediatric population.

Methods: Single centre prospective pilot study commenced after a thorough ethical review process. Children more than 12 year of age with proven gastro oesophageal reflux disease where symptoms were refractory to standard medical mangement and where fundoplication was not feasible or desirable. Pre‐procedure all patients had: ‐ ‐ Upper GI endoscopy ‐ pH impedance study ‐ Barium meal ‐ High resolution oesophageal manometry ‐ The quality of life was assessed by QOLRAD and GSRS scores. Post procedure patients were followed up at 6 weeks, 3 months, 6 months and 12 months. The objective assesem*nt at follow up was done with: ‐ ‐ pH impedance study ‐ QOLRAD and GSRS scores

Results: 8 patients have had the procedure till date out of which 5 have completed one year follow up. We experienced no technical failure. No acute or late complication occured. Patient demographics: ‐ M:F = 6:2 Median age 14.6 years (13‐16) Median weight 64.76 Kg (52.3 ‐ 86) Median height 170.09 cm (156.4 – 181.3) At one year follow up: ‐ 3 patients were off PPI with normal pH study indices and improved quality of life. 1 patient had remarkable improvement till 9 months post‐procedure but recurrence of symptoms at 1 year. 1 patient with weak swallow, failed to respond

Conclusions: STRETTA® is safe and feasible in paediatric population. Larger paediatric studies randomised to laparoscopic fundoplication required

Contact e‐mail address: shishusharma@nhs.net

CONGENITAL DUODENAL WEB DILATATION FOR ENDOSCOPY VIDEO CLIP ZONE

Shishu Sharma¹, Mike Thomson^1,2,3

¹Paediatric Gastroenterology, Sheffield's Children's Hospital, Sheffield, United Kingdom, ²Sheffield Children's Hospital, Sheffield, United Kingdom, ³Gastroenterology, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom

Objectives and Study: We present here our latest experience of dilatating a congenital duodenal web in a child with Trisomy 21. To be shared in the endoscopy video clip session

Methods: 18 month old child Trisomy 21 Faltering growth. Unsafe swallow. Planned for gastrsotomy insertion. Pre‐procedure barium meal raised suspicion of duodenal obstruction. Endoscopic view showed pin‐hole duodenal web at the level of ampulla of vater. This was dilated serially under radiological guidance to 12 mm.

Results: The duodenal web was sucessfully dilated with no immediate or late complication. A concomitant gastrostomy was also sited.

Conclusions: Duodenal webs can be effectively managed endoscopically. This case highlights the importance of barium imaging in a child with faltering growth and also as a screening tool prior to performing endoscopic gastrostomy procedures. We have published our case series of 15 patients in the past and this case further strengthens the evidence. doi:10.1016/j.jpedsurg.2019.10.025

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LOSS‐OF‐FUNCTION OF CLMP IS ASSOCIATED WITH CONGENITAL SHORT BOWEL SYNDROME AND IMPAIRED INTESTINAL DEVELOPMENT

Shanshan Chen¹, Yongtao Xiao^1,2,3, Jie Zhou¹, Wei Cai^1,2,3,4, Ying Wang^1,2,3

¹Division Of Pediatric Gastroenterology And Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, ²Shanghai Institute of Pediatric Research, Shanghai, China, ³Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China, ⁴Department Of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Objectives and Study: Congenital short bowel syndrome (CSBS) is a rare gastrointestinal disease. Coxsackie and adenovirus receptor‐like membrane protein (CLMP) mutations have been identified as a genetic risk factor of CSBS. However, the specific pathogenic mechanism remains unclear. This study aimed to explore the clinical manifestations, genetic characteristics, and molecular mechanisms underlying CSBS caused by CLMP mutations.

Methods: Whole‐exome sequencing was performed to determine the pathogenic gene mutations in children with CSBS and their family members. In addition, a zebrafish model was established by microinjecting morpholinos into zebrafish embryos to investigate the role of clmp in intestinal embryonic development. This was investigated by measuring the length of the zebrafish, evaluating gastrointestinal motility, and performing qRT‐PCR assays.

Results: Two children with CSBS had CLMP mutations, one with a c.244C>T (p.R82*) mutation and exons 3‐5 deletion, and the other with a c.23T>A (p.L8*) mutation and exons 3‐5 deletion. Interestingly, the mutations in both children were nonsense variants, resulting in the appearance of an early stop codon. After knocking down clmp expression in zebrafish embryos, the intestinal length and the gastrointestinal motility decreased (p<0.05). Furthermore, the expression of smooth muscle‐associated genes decreased significantly, including smooth muscle cell‐related genes myosin heavy chain 11a (myh11), transgelin (tagln) and actin alpha 2 (acta2) (p<0.05). Additionally, clmp mRNA partially rescued zebrafish defects caused by clmp morpholino knockdown.

Conclusions: The c.244C>T (p.R82*) or c.23T>A (p.L8*) mutations in CLMP and the deletion of exons 3‐5 are closely related to the development of CSBS. Clmp knockdown decreased intestinal transport dynamics and expression of smooth muscle‐related genes in zebrafish. Thus, CLMP is expected to be a potential gene therapeutic target for CSBS.

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IMPAIRED INTESTINAL FXR SIGNALING IS INVOLVED IN ABERRANT STEM CELL FUNCTION LEADING TO INTESTINAL FAILURE IN PEDIATRIC PATIENTS WITH SHORT BOWEL SYNDROME

Yuling Zhao, Junkai Yan, Wei Cai

Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Objectives and Study: Management of pediatric short bowel syndrome (SBS), emphasizing intestinal adaptation, depends on LGR5+ intestinal stem cells (ISC) functioning through robust mitochondrial fatty acid oxidation (FAO). Here we used intestinal organoids derived from pediatric SBS patients to address the hypothesis that intestinal failure in SBS might be resulted from depletion of LGR5+ stem cells due to impaired FXR signaling.

Methods: 14 SBS patients were enrolled in this study. Following thorough assessments of nutrition status (with malnutrition or not), PN duration (>3 months or not), and complications (with IFALD or not), they were grouped into either intestinal adapted (IA) group or intestinal failure (IF) group. Biopsies were obtained during surgery, ISC markers and FXR expression were assessed via immunofluorescence and Q‐PCR. The intestinal organoids derived from patients (PDOs) treated with 10‐50 μM tauro‐β‐muricholic acid (T‐βMCA) for 96 hours to block FXR signaling. Expression levels of ISC markers, proliferative genes, FXR and FAO genes in PDOs were analyzed via Q‐PCR and immunofluorescence, while enterocyte proliferation was assessed by EDU staining.

Results: Detailed clinical characteristics of IA patients (n=8) and IF patients (n=6) are shown in table 1. SBS‐IF patients represented significant intestinal villus atrophy, and the LGR5+ cells were lower (3.23 vs 1.82 cells/crypt, p=0.003), accompanied by reduced FXR expression. Remarkably, unlike organoids from well‐adapted patients presenting branched structures at P20, those from poorly adapted patients displayed spherical structures, the mRNA levels of LGR5 and KI67 decreased approximately by 79.80% (p<0.001) and 32.24% (p=0.011), concomitant with decreased expression of FXR. Moreover, T‐βMCA treatment efficiently reduced the population of LGR5+ cells and the proliferation rate of enterocytes. Furthermore, key FAO genes including CPT1a and ACSF2 were similarly suppressed.

Conclusions: Disrupted FXR can promote the depletion of LGR5+ISC via hampered FAO processes, offering a novel potential intervention target promoting intestinal adaptation in SBS patients.

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BUDESONIDE ORAL SUSPENSION IS EFFECTIVE AND SAFE IN PEDIATRIC EOSINOPHILIC ESOPHAGITIS (EOE): RESULTS FROM THE INDUCTION PHASE OF THE RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐CONTROLLED TRIAL PEDEOS‐1

Alfredo Lucendo¹, Henedina Antunes², Alexandra Papadopoulou³, Marcus Auth⁴, Shoma Dutt⁵, Hankje Escher⁶, Michiel Van Wijk⁷, Gloria Domínguez‐Ortega⁸, Carolina Gutiérrez‐Junquera⁹, Noam Zevit¹⁰, Tsili Zangen¹¹, Eunice Trindade¹², Maria Fotoulaki¹³, Buket Dalgic¹⁴, Ana Isabel Lopes¹⁵, Sara Feo‐Ortega¹, Filipa Neiva², Vasiliki Maria Karagianni³, Maria Rogalidou³, Danielle Hendriks⁶, Carlijn Mussies⁷, Nuria Puente Ubierna⁸, Maria Céu Espinheira¹², Helena Loreto¹⁵, Michael Vieth¹⁶, Sarah Burrack¹⁷, Ralph Mueller¹⁸, Roland Greinwald¹⁸, Jorge Amil Dias¹²

¹Dept. Of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain, ²Gastroenterology, Hepatology And Nutrition Pediatric Unit And Clinic Academic Center, Hospital de Braga, Braga, Portugal, ³Division Of Gastroenterology And Hepatology, First Department Of Pediatrics, University Of Athens, Children's Hospital Agia Sofia, Athens, Greece, ⁴Department Of Paediatric Gastroenterology, Hepatology And Nutrition, Alder Hey Children's NHS Foundation Trust and University of Liverpool, Liverpool, United Kingdom, ⁵Department Of Gastroenterology, The Children's Hospital At Westmead, The Sydney Children's Hospitals Network, Westmead, Australia, ⁶Paediatric Gastroenterology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands, ⁷Vrije Universiteit, Pediatric Gastroenterology, Emma Children's Hospital ‐ Amsterdam UMC, Amsterdam, Netherlands, ⁸Gastroenterology And Nutrition Department, Niño Jesús University Children Hospital, Madrid, Spain, ⁹Pediatric Gastroenterology Unit, University Hospital Puerta De Hierro‐majadahonda, Autonomous University of Madrid, Madrid, Spain, ¹⁰Institute Of Gastroenterology, Hepatology, And Nutrition, Schneider Children's Medical Center Of Israel, Faculty Of Medicine, Schneider Children's Medical Center of Israel, Petah Tikva, Israel, ¹¹Pediatric Gastroenterology And Nutrition Unit, Wolfson medical center, Holon, Israel, ¹²Pediatric Gastroenterology And Nutrition Unit, Department Of Pediatrics, Centro Hospitalar Universitário São João, Porto, Portugal, ¹³Department Of Pediatrics, Medical School, Aristotle University Of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece, ¹⁴Departments Of Paediatric Gastroenterology, Gazi University Medical School, Ankara, Turkey, ¹⁵Pediatric Gastroenterology Unit, Department Of Pediatrics, University Hospital Santa Maria ‐ CHULN and Medical School, University of Lisbon ‐ CAML, Lisbon, Portugal, ¹⁶Institute Of Pathology, Friedrich‐alexander‐university Erlangen‐nuremberg, Klinikum Bayreuth, Bayreuth, Germany, ¹⁷Clinical Research, Dr. Falk Pharma GmbH, Freiburg Im Breisgau, Germany, ¹⁸Clinical Research, Dr. Falk Pharma GmbH, Freiburg im Breisgau, Germany

Objectives and Study: To assess efficacy and safety of two doses of a novel budesonide oral suspension (BOS) versus placebo for induction of histological remission with clinical response in pediatric EoE patients.

Methods: 76 patients aged 2‐11 (stratum I; n=35) and 12‐17 (stratum II; n=41) were randomized to high‐dose BOS (BOS‐H: 0.5 mg/1 mg (stratum I/II) twice daily [BID]; n=26), low‐dose BOS (BOS‐L: 0.5 mg/1 mg (stratum I/II) BOS once daily [OD]; n=26) or placebo (n=24). The composite primary endpoint was the proportion of patients with both histological remission (peak eos: <16 eos/mm² hpf [<5 eos/hpf]) and clinical response (≥30% decrease in Pediatric EoE Symptom Severity Module, version 2.0 (PEESS v2.0)) at week 12. Secondary endpoints included proportion of patients with histological remission, clinical response or dysphagia resolution (≤ 2 on a 0–10‐point numerical rating scale (NRS)) and a change in modified endoscopic reference score (EREFS) or in EoE histological scoring system (EoEHSS).

Results: BOS‐H and BOS‐L were both superior to placebo in achieving the composite primary endpoint (69.2% and 46.2% vs. 0%; both p<.0001). The data are confirmed with the histological and EREFS scores (Table 1). Differences in clinical response (PEESS) were not demonstrated, while dysphagia (NRS) was numerically improved in both BOS groups versus placebo. Esophageal candidiasis occurred in one BOS‐H patient (3.8%), while decreased morning serum cortisol levels occurred in one patient in BOS‐H and one in the placebo group. Neither adrenal suppression (assessed clinically and via ACTH test) nor any serious adverse reaction to BOS was reported.

Conclusions: BOS was effective and safe in inducing histological remission with clinical response in pediatric EoE patients, with clinically relevant better results obtained with BOS‐H (incl. histological and endoscopic secondary endpoints). Clinical response rates based on PEESS v2.0 were comparable, while improvement in dysphagia assessed via NRS was more common in the BOS groups compared with placebo.

Contact e‐mail address: sarah.burrack@drfalkpharma.de

DUPILUMAB IMPROVES CAREGIVER‐REPORTED EOSINOPHILIC ESOPHAGITIS (EOE) SYMPTOMS IN CHILDREN AGED 1 TO < 12 YEARS WITH EOE: 16‐WEEK RESULTS FROM PHASE 3 EOE KIDS STUDY

Marc Rothenberg¹, Dhandapani Ashok², Salvatore Oliva³, Changming Xia⁴, Tiffany Pela⁵, Sandy Durrani⁴, Juby Jacob‐Nara⁴, Amr Radwan⁴, Sarette Tilton⁵, Ryan Thomas⁴

¹Division Of Allergy And Immunology, Department Of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, United States of America, ²Department Of Paediatrics, Western University, London, Canada, ³Maternal And Child Health Department, Pediatric Gastroenterology And Liver Unit, Sapienza ‐ University of Rome, Rome, Italy, ⁴Regeneron Pharmaceuticals Inc., Tarrytown, United States of America, ⁵Sanofi, Bridgewater, United States of America

Objectives and Study: EoE, a chronic, progressive, type 2 inflammatory disease, has no medications currently indicated in children aged <12 years. Dupilumab is a fully human monoclonal antibody that blocks interleukin (IL)‐4 and IL‐13, key drivers of type 2 inflammation. We assessed the impact of dupilumab on EoE symptoms, using the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) version 2.0 (caregiver version), in children aged 1–<12 years with active EoE in the placebo‐controlled Part A of the Phase 3 EoE KIDS trial (NCT04394351).

Methods: The PEESSv2.0 comprises 20 items (items scored 0–4; higher scores indicate greater burden) assessing frequency (11 questions) and severity (9 questions) of symptoms and adaptive behaviors, containing 4 subdomains: dysphagia, nausea/vomiting, gastroesophageal reflux disease, and pain. PEESSv2.0 was evaluated at baseline and Week (W) 16 in EoE KIDS; total, frequency, severity, domain (all scored 0–100), and individual item scores were compared in patients treated with dupilumab higher‐exposure, lower‐exposure or placebo. Reported p‐values are nominal.

Results: Baseline characteristics were similar in dupilumab higher‐exposure (n=37) and placebo (n=34) groups. Baseline mean PEESSv2.0 total scores were 38.0 and 38.3, respectively. At W16, PEESSv2.0 total was reduced with dupilumab higher‐exposure vs placebo (least squares [LS] mean change [95% confidence interval (CI)] ‐19.86 [‐24.98, ‐14.74] vs ‐11.83 [‐17.61, ‐6.05] respectively; LS mean difference [95% CI] ‐8.03 [‐15.39, ‐0.67], p <0.05). All domain sub‐scores were numerically reduced with dupilumab higher‐exposure vs placebo at W16 (Figure); nominal significance was observed in frequency, dysphagia, and nausea/vomiting domains. In patients on the lower‐exposure dupilumab regimen, effects were generally either comparable or numerically lower than with the higher‐exposure regimen.

Conclusions: Dupilumab higher‐exposure led to improvement in PEESSv2.0 total score vs placebo at W16 in EoE KIDS. Frequency, dysphagia, and nausea/vomiting domains were improved with nominal significance, though all domains were improved numerically with dupilumab vs placebo.

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SINGLE CELL ANALYSIS TO CHARACTERIZE MUCOSAL T‐CELL INFLAMMATION DURING DISEASE TRAJECTORY IN PAEDIATRIC EOSINOPHILIC ESOPHAGITIS

Hannes Hoelz¹, Tim Faro¹, Simon Buehler¹, Anja Jurk¹, Marie‐Luise Frank¹, Sabrina Wagner², Matthias Warkotsch², Sebastian Jarosch², Monica Matchado³, Eberhard Lurz¹, Theresa Foerg¹, Mohammad‐Samer Hajji^1,4, Sibylle Koletzko^1,5, Dirk Busch², Markus List³, Susanna Mueller⁶, Tobias Schwerd¹

¹Department Of Paediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany, ²Institute of medical microbiology, immunology and hygiene, Technical University of Munich (TUM), TUM School of Medicine, Munich, Germany, ³Experimental Bioinformatics, TUM School of Life Sciences, TUM Freising, Freising, Germany, ⁴Department of Pediatrics, Schwabing Hospital, Munich, Germany, ⁵Department Of Pediatrics, Gastroenterology And Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland, ⁶Institute of Pathology, Ludwig Maximilian University (LMU), University Hospital, Munich, Germany

Objectives and Study: Therapy targeting the interleukin‐13/4 axis is effective in eosinophilic esophagitis (EoE), suggesting an important role of T_H2‐cells in inflammation. To better understand T‐cell response, we analyzed gene expression in esophageal tissue and isolated T‐cells.

Methods: Clinical data and esophageal biopsies were collected from paediatric patients with EoE at diagnosis and up to six follow‐up visits under guideline conform therapy. Patients with gastroesophageal reflux disease (GERD) and functional disorders (FD) served as inflammatory and non‐inflammatory controls. Active EoE was defined as ≥15 and histologic remission as <15 eosinophils/hpf. Human RNA was extracted from esophageal biopsies for bulk RNA sequencing. Isolated CD45⁺CD3⁺ cells from esophageal biopsies were analyzed by single‐cell analysis (10X Genomics).

Results: Biopsies of 50 patients with EoE (mean age: 10.2 years, 50% male) from 121 endoscopies were investigated compared to biopsies from controls (GERD: N=33, FD: N=67). After nine months 83% of patients with EoE were in histologic remission. The tissue transcriptome (biopsies: n=100; patients: EoE: N=29, GERD: N=16, FD: N=27) showed 27 significantly differentially expressed genes (DEG; fold change >2.0) associated with active EoE and still elevated in remission compared to controls. These genes were associated with cell‐cell contacts and immunomodulation (ACTG2, CDH26, CXCL1), as well as lipid peroxidation (ALOX15), among others. Single cell analysis (biopsies: n=94; patients: EoE: N=32, GERD/FD: N=12) showed that in active EoE GATA3⁺IL13⁺T_H2‐cells (p=0.0202) and FOXP3⁺CTLA4⁺IL10^hi regulatory T‐cells (Tregs, p=0.0283) were significantly increased compared with EoE in remission. RORC⁺IL‐17⁺IL‐22⁺T_H17‐cells correlated negatively with esophageal eosinophilia (R=‐0.43, p=0.006). The clonal expansion of T‐cell receptors in active EoE was pronounced in activated CD8⁺T‐cells. Individual T‐cell clones persisted in individual remission phases.

Conclusions: Even after resolution of inflammation, genes are differentially expressed in EoE. T_H2‐cells and IL10^hiTregs are associated with active EoE. The role of activated CD8⁺T‐cells and T_H17‐cells in EoE remains to be elucidated.

Contact e‐mail address: hannes.hoelz@med.uni‐muenchen.de

PREVALENCE OF EOSINOPHILIC ESOPHAGITIS AMONG PATIENTS WITH ESOPHAGEAL ATRESIA: A SYSTEMATIC REVIEW AND SINGLE‐ARM META‐ANALYSIS

Rian Lima¹, Vanio Do Livramento Junior², Rafael Machado³, Angelica Nau⁴

¹Fortaleza University, Fortaleza, Brazil, ²Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil, ³University of Southern Santa Catarina, Palhoça, Brazil, ⁴Pediatric Gastroenterology Division, Hospital Jaragua, Jaragua do Sul, Brazil

Objectives and Study: Esophageal atresia (EA) is the most common congenital malformation of the esophagus and may predispose to chronic inflammatory disorders, such as eosinophilic esophagitis (EoE), leading to a high disease burden. EoE has been under‐recognized in EA, which may result in inappropriate management. This meta‐analysis aimed to assess the prevalence of EoE in the EA population.

Methods: We conducted a systematic review and single‐arm meta‐analysis in line with MOOSE guidelines. PubMed, EMBASE, and Cochrane databases were searched for studies reporting the prevalence of EoE in patients with EA. Prevalence of other atopic comorbidities and the response to proton pump inhibitor (PPI) therapy in this group were also computed. We performed a single‐arm meta‐analysis of proportions using a random‐effects general linear mixed model in R software version 4.3.2.

Results: Nine studies were included (three prospective cohorts, four retrospective cohorts, two cross‐sectional), comprising 1,163 patients with EA. The pooled prevalence of EoE in this population was 11.2% (95% CI 7.1 to 17.4%; Figure 1). Mean age at diagnosis of EoE was 4.72 years (1‐14), and 65.7% were male. The prevalence of other atopic diseases, such as asthma, food allergy, rhinitis, and eczema, was 59.5% (95% CI 42.7% to 74.2%) and 43.6% (95% CI 21.2% to 69%) of patients had a positive response to PPI therapy.

Conclusions: In this meta‐analysis, we identified an 11.2% pooled prevalence of EoE among pediatric patients with EA. This finding suggests that a diagnostic evaluation for EoE may be warranted in this patient population.

Contact e‐mail address: angel.l.nau@gmail.com

DUPILUMAB IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS AND PRIOR USE OF SWALLOWED TOPICAL CORTICOSTEROIDS: RESULTS FROM THE EOE‐KIDS STUDY

Mirna Chehade¹, Salvatore Oliva², Dhandapani Ashok³, Ruiqi Liu⁴, Jennifer Maloney⁴, Raolat Abdulai⁵, Lila Glotfelty⁵, Arsalan Shabbir⁴

¹Mount Sinai Center For Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, United States of America, ²Pediatric Gastroenterology And Liver Unit, Maternal And Child Health Department, Sapienza – University of Rome, Rome, Italy, ³Department Of Paediatrics, Western University, London, Canada, ⁴Regeneron Pharmaceuticals Inc., Tarrytown, United States of America, ⁵Sanofi, Bridgewater, United States of America

Objectives and Study: We assessed the efficacy of dupilumab in children with eosinophilic esophagitis (EoE) with/without prior use of swallowed topical corticosteroids (STC) in the Phase 3 EoE‐KIDS study.

Methods: Eligible patients were aged 1 to <12 years with EoE unresponsive to proton pump inhibitors. In Part A, patients were randomized to weight‐tiered dupilumab higher‐exposure or lower‐exposure regimens, or pooled placebo for 16 weeks. Efficacy was assessed by prior use of STC status at Week 16.

Results: Of the 102 patients who entered the study, most (80.4%) had a history of STC therapy. At Week 16, the proportion of patients with ≤6 eosinophils per high‐power field in patients with/without prior STC was 60.7%/88.9% in the dupilumab higher‐exposure group, and 0%/14.3% in the placebo group (Table). Overall, improvements in additional efficacy endpoints across patients with/without a history of STC were observed with the dupilumab higher‐exposure regimen versus placebo at Week 16, including histologic, endoscopic, and symptomatic outcomes. Improvements in these efficacy measures were also observed with the lower‐exposure dupilumab regimen versus placebo at Week 16; however, effects were generally either comparable or numerically lower with the lower‐exposure dupilumab regimen than with the higher‐exposure dupilumab regimen.

Conclusions: In children with EoE in the EoE‐KIDS study, dupilumab led to improvements in histologic, symptomatic, and endoscopic aspects of EoE versus placebo regardless of prior use of STC.

Contact e‐mail address:

EFFECT OF DUPILUMAB ON WEIGHT IN PEDIATRIC PATIENTS AGED 1 TO < 12 YEARS WITH ACTIVE EOE ENROLLED IN THE PHASE 3 KIDS STUDY

Salvatore Oliva¹, Mirna Chehade², Robert Pesek³, Calies Menard‐Katcher⁴, Iris Gutmark‐Little⁵, Ruiqi Liu⁶, Jennifer Maloney⁶, Raolat Abdulai⁷, Lila Glotfelty⁷, Arsalan Shabbir⁶

¹Pediatric Gastroenterology And Liver Unit, Maternal And Child Health Department, Sapienza – University of Rome, Rome, Italy, ²Mount Sinai Center For Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, United States of America, ³Division Of Allergy/immunology, Department Of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, United States of America, ⁴Division Of Gastroenterology Hepatology And Nutrition, Department Of Pediatrics, University of Colorado School of Medicine, Gastrointestinal Eosinophilic Diseases Program, Digestive Health Institute, Children's Hospital Colorado, Aurora, United States of America, ⁵Division Of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America, ⁶Regeneron Pharmaceuticals Inc., Tarrytown, United States of America, ⁷Sanofi, Bridgewater, United States of America

Objectives and Study: There are no approved treatments for eosinophilic esophagitis (EoE) in children aged <12 years. This analysis assessed the effect of dupilumab vs placebo on weight in patients aged 1 to <12 years with active EoE enrolled in the phase 3 KIDS study (NCT04394351).

Methods: Part A was a 16‐week, double‐blind treatment period; patients were randomized 2:2:1:1 to weight‐tiered, higher‐ or lower‐exposure dupilumab regimen or placebo (2 groups). Patients who completed Part A were eligible to enter a 36‐week, extended treatment period (Part B) in which dupilumab patients continued the same dupilumab regimen and placebo patients switched to pre‐assigned higher‐exposure or lower‐exposure dupilumab. Endpoints (Weeks 16 and 52) were change from baseline in: body weight‐for‐age percentile, body mass index (BMI)‐for‐age z‐score for patients aged ≥2 years, weight‐for‐age z‐score, and weight‐for‐length z‐score.

Results: At Week 16, mean change from baseline in body weight‐for‐age percentile was +3.09 vs +0.29 for higher‐exposure dupilumab vs placebo; change in BMI‐for‐age z‐score was +0.10 vs ‒0.14 and change in weight‐for‐age z‐score was +0.12 vs ‒0.01. At Week 52, improvements were maintained or increased with continued higher‐exposure dupilumab; improvements were also observed in placebo patients who switched to higher‐exposure dupilumab (Table). Dupilumab safety was consistent with the known dupilumab safety profile.

Conclusions: Higher‐exposure dupilumab was associated with a greater increase in body weight‐for‐age percentile at Weeks 16 and 52 vs placebo. Higher‐exposure dupilumab was associated with sustained trends for increased BMI‐for‐age and weight‐for‐age z‐scores vs placebo.

Contact e‐mail address:

ESOPHAGEAL DYSMOTILITY IN PATIENTS WITH HISTOLOGIC REMISSION OF EOSINOPHILIC ESOPHAGITIS

Dotan Yogev¹, Lev Dorfman², Sherief Mansi², Khalil El‐Chammas², John Lyles³, Vincent Mukkada², Ajay Kaul²

¹Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel, ²Division Of Gastroenterology, Hepatology, And Nutrition, Cincinnati Childrens Hospital Medical Center, Cincinnati, United States of America, ³Division Of Pediatric Gastroenterology, Hepatology, And Nutrition, Department of Pediatrics, Duke University School of Medicine, Duke University Hospital, Durham, United States of America

Objectives and Study: Dysphagia is a frequent symptom of active Eosinophilic Esophagitis (EoE), but at times it persists despite attaining histologic healing and lack of fibro‐stenotic changes. We aimed to describe the manometric findings in this subset of patients.

Methods: A retrospective review of charts over a 10‐year period at a tertiary pediatric gastroenterology center (Cincinnati Children's Hospital Medical Center), treating roughly 1,500 EoE patients per year. Children diagnosed with EoE were included if they were referred to high‐resolution impedance manometry (HRIM) to investigate persistent dysphagia despite histologic healing (<15 eos/hpf). Data including initial EoE diagnosis, endoscopy reports, esophageal biopsies, treatment regimens and HRIM were retrospectively collected.

Results: The estimated prevalence of post‐remission dysphagia in our cohort was exceedingly rare (<0.05%). Four patients met the eligibility criteria of histologic remission and absence of fibro‐stenotic features on endoscopic evaluation and thus, were included in this case series. Patients achieved remission with steroids, PPI or both within a median time of 5 months from EoE diagnosis. Peak Eosinophil count at remission was ≤5 Eos/hpf in 3 patients and ≤10 Eos/hpf in one (table 1). On HRIM (figure 1), all 4 patients had a hypomotile esophagus and abnormal bolus clearance. Lower esophageal sphincter IRP values were normal in three patients and elevated in one. Two patients were diagnosed with ineffective esophageal motility, 1 with aperistalsis, and 1 was diagnosed with achalasia type 1.

Conclusions: Post‐remission dysphagia is rare in EoE. Esophageal dysmotility with a hypomotile pattern may contribute to the persistent dysphagia in children with EoE. HRIM should be considered in patients with EoE in whom symptoms persist despite histologic remission.

Contact e‐mail address:

MALE GENDER INFLUENCES NEGATIVELY THE 1‐YEAR OUTCOME OF LIVE‐BORN CHILDREN WITH OESOPHAGEAL ATRESIA

Judith Dapvril Guidet¹, Alexandre Lapillonne², Arnaud Bonnard³, Nicolas Caron⁴, Thierry Merrot⁵, Catherine Jacquier⁶, Sabine Irtan⁷, Thierry Lamireau⁸, Audrey Guinot⁹, Virginie Fouquet¹⁰, Isabelle Talon¹¹, Aurélie Le Mandat¹², Laure Bridoux Henno¹³, Dominique Forgues¹⁴, Frédéric Elbaz¹⁵, Nicolas Berte¹⁶, Marie‐Laurence Polimerol¹⁷, Jean‐Luc Michel¹⁸, Aurore Haffreingue¹⁹, Philippe Buisson²⁰, Jean‐François Lecompte²¹, Michel Francois²², Hubert Lardy²³, Diana Potop²⁴, Corinne Borderon²⁵, Françoise Schmitt²⁶, Aurélien Scalabre²⁷, Frédéric Auber²⁸, Philine De Vries²⁹, Cécile Pelatan³⁰, Cécilia Tolg³¹, Olivier Jaby³², Myriam Pouzac³³, Céline Grosos³⁴, Hélène Behal¹, Frederic Gottrand¹, Madeleine Aumar¹

¹Paediatric Gastroenterology, Hepatology, And Nutrition, Univ Lille, CHU Lille, Inserm U1286 Infinite, CHU Lille Pôle Enfant, Lille, France, ²Centre Hospitalier Universitaire APHP Necker‐Enfants Malades, Paris, France, ³Centre Hospitalier Universitaire APHP Robert Debré, Paris, France, ⁴Centre Hospitalier Universitaire de Lyon, Lyon, France, ⁵Centre Hospitalier Universitaire de Marseille, Marseille, France, ⁶Centre Hospitalier Universitaire de Grenoble Alpes,, Grenoble, France, ⁷Centre Hospitalier Universitaire APHP Armand Trousseau, Paris, France, ⁸Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France, ⁹Centre Hospitalier Universitaire de Nantes, Nantes, France, ¹⁰Centre Hospitalier Universitaire APHP, Paris, France, ¹¹Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France, ¹²Centre Hospitalier Universitaire de Toulouse, toulouse, France, ¹³Centre Hospitalier Universitaire de Rennes, Rennes, France, ¹⁴Centre Hospitalier Universitaire de Montpellier, montpellier, France, ¹⁵Centre Hospitalier Universitaire de Rouen, rouen, France, ¹⁶Centre Hospitalier Universitaire de Nancy, nancy, France, ¹⁷Centre Hospitalier Universitaire de Reims, reims, France, ¹⁸Centre Hospitalier Universitaire de Réunion, la Réunion, France, ¹⁹Centre Hospitalier Universitaire de Caen, caen, France, ²⁰Centre Hospitalier Universitaire d'Amiens, Amiens, France, ²¹Centre Hospitalier Universitaire de Nice, nice, France, ²²Centre Hospitalier Universitaire de Dijon, dijon, France, ²³Centre Hospitalier Universitaire de Tours, Tours, France, ²⁴Centre Hospitalier Universitaire de Poitiers, poitiers, France, ²⁵Centre Hospitalier Universitaire de Clermont‐Ferrand, Clermont‐Ferrand, France, ²⁶Centre Hospitalier Universitaire de Angers, Angers, France, ²⁷Centre Hospitalier Universitaire de Saint‐Etienne, Saint Etienne, France, ²⁸Centre Hospitalier Universitaire de Besançon, Besançon, France, ²⁹Centre Hospitalier Universitaire de Brest, Brest, France, ³⁰Centre Hospitalier du Mans, Le Mans, France, ³¹Centre Hospitalier Universitaire de Fort de France, Fort de France, France, ³²Centre Hospitalier Intercommunal de Créteil, Créteil, France, ³³Centre Hospitalier Universitaire d'Orléans, Orléans, France, ³⁴Centre Hospitalier Universitaire de Limoges, Limoges, France

Objectives and Study: Œsophageal atresia (OA) is more frequent in boys than in girls like other congenital malformations. Few studies have suggested that male gender was a risk factor for increased respiratory and digestive complications. Our objective was to assess if male gender was associated with the first‐year outcome.

Methods: This prospective, multicentric, observational population‐based study analysed the data of every child included in our national registry of OA born between January 2008 and December 2019. We registered prenatal information, surgery, and the first‐year outcome including mortality, surgical complication, nutritional outcome, and respiratory and digestive complications. A univariate statistical analysis was performed. Missing data were imputed using the multiple imputation method.

Results: We included 1939 patients (58.7% of boys, 91% OA with tracheal oesophageal fistula). There were no significant differences regarding neonatal characteristics and type of OA based on gender. We observed no difference in mortality rate between groups. At 1 year of age, the prevalence of anastomotic stricture and undernutrition was more frequent in boys than in girls (respectively 27.7% vs. 23.3%, p<0.01 and 9.2% vs. 5.25%, p<0.01). Boys required respiratory treatment and hospital readmission more frequently than girls during their first year (respectively 37% vs. 29%, p<0.01, and 82% vs. 75.2%, p<0.01).

Conclusions: Our study highlights that male gender influences nutritional, digestive, and respiratory outcomes at one year in OA. Underlying mechanisms are to date unknown, but it appears that boys operated at birth for OA require special medical attention during their first year of life.

Contact e‐mail address: judith.dapvril@chu‐lille.fr

NUTRITIONAL STATUS AT THE AGE OF 6 YEARS OF CHILDREN OPERATED ON AT BIRTH FOR OESOPHAGEAL ATRESIA: A PROSPECTIVE LONGITUDINAL COHORT

Eugénie Bitoumbou¹, Arnaud Bonnard², Alexandre Lapillonne³, Matthieu Antoine¹, Catherine Jacquier⁴, Nicolas Caron⁵, Audrey Guinot⁶, Thierry Lamireau⁷, Sabine Irtan⁸, Laure Bridoux Henno⁹, Clémentine Dumant¹⁰, Anne Breton¹¹, Joséphine Lirussi‐Borgnon¹², Isabelle Talon¹³, Alexandre Fabre¹⁴, Nicoleta Panait¹⁵, Aline Ranke‐Chrétien¹⁶, Francesco Laconi¹⁷, Virginie Fouquet¹⁸, Nicolas Kalfa¹⁹, Djamal‐Dine Djeddi²⁰, Stephanie Willot²¹, Claire Dupont²², Anne Turquet²³, Clara Crémilleux²⁴, Françoise Schmitt²⁵, Corinne Borderon²⁶, Olivier Jaby²⁷, Myriam Pouzac²⁸, Cécile Pelatan²⁹, Aurélie Comte³⁰, Philine De Vries³¹, Laurent Fourcade³², Valérie Triolo³³, Cécilia Tolg³⁴, Stephan Geiss³⁵, Hélène Behal³⁶, Madeleine Aumar¹, Frederic Gottrand¹

¹Paediatric Gastroenterology, Hepatology, And Nutrition, Univ Lille, CHU Lille, Inserm U1286 Infinite, CHU Lille Pôle Enfant, Lille, France, ²Centre Hospitalier Universitaire APHP Robert Debré, Paris, France, ³Centre Hospitalier Universitaire APHP Necker‐Enfants Malades, Paris, France, ⁴Centre Hospitalier Universitaire de Grenoble Alpes,, Grenoble, France, ⁵Centre Hospitalier Universitaire de Lyon, Lyon, France, ⁶Centre Hospitalier Universitaire de Nantes, Nantes, France, ⁷Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France, ⁸Centre Hospitalier Universitaire APHP Armand Trousseau, Paris, France, ⁹Centre Hospitalier Universitaire de Rennes, Rennes, France, ¹⁰Centre Hospitalier Universitaire de Rouen, Rouen, France, ¹¹Centre Hospitalier Universitaire de Toulouse, Toulouse, France, ¹²Centre Hospitalier Universitaire de Dijon, Dijon, France, ¹³Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France, ¹⁴Centre Hospitalier Universitaire de Marseille Timone, Marseille, France, ¹⁵Centre Hospitalier Universitaire de Marseille Nord, Marseille, France, ¹⁶Centre Hospitalier Universitaire de Nancy, Nancy, France, ¹⁷Centre Hospitalier Universitaire de Reims, Reims, France, ¹⁸Centre Hospitalier Universitaire APHP Kremlin Bicêtre, Paris, France, ¹⁹Centre Hospitalier Universitaire de Montpellier, Montpellier, France, ²⁰Centre Hospitalier Universitaire d'Amiens, Amiens, France, ²¹CHU, Tours, France, ²²Department Of Pediatrics, Caen University Hospital, Caen, France, ²³Centre Hospitalier Universitaire de La Réunion, Saint Denis de la Réunion, France, ²⁴Centre Hospitalier Universitaire de Saint‐Etienne, Saint‐Etienne, France, ²⁵Centre Hospitalier Universitaire de Angers, Angers, France, ²⁶Centre Hospitalier Universitaire de Clermont‐Ferrand, Clermont‐Ferrand, France, ²⁷Centre Hospitalier Intercommunal de Créteil, Créteil, France, ²⁸Centre Hospitalier Universitaire d'Orléans, Orléans, France, ²⁹Centre Hospitalier du Mans, Le Mans, France, ³⁰Centre Hospitalier Universitaire de Besançon, Besançon, France, ³¹Centre Hospitalier Universitaire de Brest, Brest, France, ³²Centre Hospitalier Universitaire de Limoges, Limoges, France, ³³Centre Hospitalier Universitaire de Nice, Nice, France, ³⁴Centre Hospitalier Universitaire de Fort‐de‐France, Fort‐de‐France, France, ³⁵Centre Hospitalier de Colmar, Colmar, France, ³⁶Centre Hospitalier Universitaire de Lille, EA 2694 ‐ Santé Publique: Épidémiologie et Qualité des Soins, Unité de Biostatistiques, Lille, France

Objectives and Study: Due to motility abnormalities and digestive complications, oesophageal atresia (OA) affects food intake and possibly nutritional status. Undernutrition has been shown to affect about 15% of the patients at the age of one year, but the long‐term nutritional outcome of these patients remains poorly studied. Our objective was to assess the prevalence and predictive factors of undernutrition and stunting of patients at 6 years old.

Methods: We conducted a prospective, multicentric, nested cohort study. Data of every consecutive patient born in France with OA between 2010 and 2012 were recorded and merged with data collected at birth and 1 year of age in our national registry of OA. Undernutrition and stunting were defined by Z‐scores of Body Mass Index (BMI) and height‐for‐age (HFA) ratio less than ‐2 standard deviations, respectively. Uni‐ and multivariate analyses were performed thanks to the imputation of missing data.

Results: We included 449 of the 468 eligible patients (92%). Prevalence of undernutrition and stunting at 6 years was respectively 9.0% and 11.1%. Undernutrition at one year of age was the only independent factor predictive for undernutrition at the age of 6 (OR 4.37 (IC95% 1.77 to 10.77), p=0.002), while being small for gestational age, a congenital heart malformation and preexisting stunting at one year were independent factors predictive for stunting at 6 years (OR 2.32 (IC95% 1.01 to 5.33),p = 0.048, OR 1.99 (IC95% 1.00 to 3.93), p = 0.049; and OR 5.51 (IC95% 2.31 to 13.18), p=0.0002, respectively).

Conclusions: Our study highlights that undernutrition and stunting remain frequent in the middle‐term follow‐up in OA and originate mainly during the first year of life.

Contact e‐mail address: eugenie.bitoumbou@chu‐lille.fr

CATHETER RELATED BLOODSTREAM INFECTIONS WITH STAPHYLOCCOCUS AUREUS IN PEDIATRIC PATIENTS WITH CHRONIC INTESTINAL FAILURE RECEIVING HOME PARENTERAL NUTRIITON: CATHETER SALVAGE VERSUS REMOVAL, WHAT TO DO?

Aysenur Demirok¹, David Illy², Sietse Nagelkerke³, Michiel Lagerweij⁴, Marc Benninga¹, Merit Tabbers¹

¹Pediatric Gastroenterology And Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, ²Emma Children's Hospital, Amsterdam, Netherlands, ³2. Pediatric Immunology, Rheumatology and Infectious DiseaseEmma Children's Hospital, Amsterdam, Netherlands, ⁴3. Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, Netherlands

Objectives and Study: Children with chronic intestinal failure (IF) require long‐term home parenteral nutrition (HPN), administered through a central venous catheter. Catheter related blood stream infection (CRBSI) with Staphylococcus aureus (S. aureus) is known to be a serious infection with a high mortality rate and a high risk of complications. A standardized protocol on management of S. aureus bloodstream infections in children on long‐term parenteral nutrition is currently lacking. The aim of this study is to evaluate the effectiveness and safety of the current management in the Emma Children's Hospital, an HPN expertise center in the Netherlands.

Methods: Retrospective cohort study consisting of all patients 0‐18 years with chronic intestinal failure on home parenteral nutrition treated between 2013‐2022. Primary outcomes were incidence per 1000 catheter days, catheter salvage attempt rate and successful catheter salvage rate. Secondary outcomes included complications related to S. aureus CRBSI and mortality.

Results: A total of 74 patients (39 male, 53%) were included covering 327.8 catheter years. Twenty‐eight patients (38%) had a total of 52 S. aureus CBRSIs with an incidence rate of 0.4 per 1000 catheter days. The catheter salvage attempt rate was 44% (23/52). Successful catheter salvage rate was 100%. No relapse (re‐infection within 30 days) occurred and no removal was needed after catheter salvage. A total of 5/52 (10%) S. aureus CRBSI episodes in 4 patients were associated with complications at admission and included arthritis and febrile convulsions. All complications that occurred were already present at admission and were not related to salvage or removal of catheter. No patients died because of a S. aureus CRBSI.

Conclusions: Catheter salvage in S. aureus CRBSI in pediatric patients with home parenteral nutrition can safely be attempted after careful consideration by a multidisciplinary team in an expertise HPN center.

Contact e‐mail address: a.demirok@amsterdamumc.nl

TRANSITION OF CHILDREN WITH CHRONIC BOWEL AND LIVER DISEASE TO ADULT CARE: A MULTICENTER ASIAN SURVEY OF PAEDIATRIC GASTROENTEROLOGISTS

Shu Ching Ee¹, Sunitha Vimalesvaran¹, Way Lee², Sup*rn Treepongkaruna³, Nuthapong Ukarapol⁴, Felizardo Gatcheco⁵, Takashi Ishige⁶, Hong Koh⁷, Shaman Rajindrajith⁸, Nikhil Thapar^9,10,11,12, Marion Margaret Aw^13,14

¹Paediatrics, National University Hospital, Singapore, Singapore, ²Department Of Paediatrics, Faculty Of Medicine, University of Malaya, Kuala Lumpur, Malaysia, ³Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, ⁴Chiang Mai University, Chang Wat Chiang Mai, Thailand, ⁵Pediatrics, Manila Central University Hospital, Caloocan, Philippines, ⁶Department Of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan, ⁷Department Of Pediatrics, Yonsei Univeresity College of Medicine, Seoul, Korea, Republic of, ⁸University of Colombo, Colombo, Sri Lanka, ⁹Queensland Children's Hospital, Brisbane, Australia, ¹⁰School of Medicine, University of Queensland, Brisbane, Australia, ¹¹Queensland Children's Hospital, Department of Gastroenterology, Hepatology, and Liver Transplant, Brisbane, Australia, ¹²Gastroenterology, Hepatology And Liver Transplant Unit, Children's Health Queensland Hospital and Health Service, Queensland Children's Hospital, South Brisbane, Australia, ¹³Paediatrics, Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, Singapore, ¹⁴National University Singapore, Singapore, Singapore

Objectives and Study: The rising incidence of chronic gastrointestinal conditions and better survival of children with previously life‐limiting diseases have resulted in the need for continuity of care into adulthood. This study aimed to detail the current state of transition services for paediatric gastroenterology and hepatology in Asia‐Pacific region.

Methods: Paediatric gastroenterologists were invited to participate via a web‐based survey administered through a regional paediatric gastroenterology society. The questionnaire was designed based on the Transition Readiness Assessment Questionnaire (5.0) and Barriers to Transition care in IBD Questionnaire.

Results: One‐hundred‐and‐nine paediatric gastroenterologists from 10 countries participated. Respondents felt the ideal age of transition was 18 years (59%), 21 years (17%), and 15 years (6%). Factors highly perceived as important in deciding timing of transfer were patients demonstrating responsibility for their own care (mean 3.5± SD 0.6, scale of 1‐4 with 1=not important, 4=very important),having knowledge about the disease and expectation (mean 3.40±SD 0.7), and emergence of adult‐related health issues (mean 3.38±SD 0.8). Most clinicians would begin the process 2 years before complete transfer. Whilst all felt transition services were important and 90% were interested in it, only 59% were providing transition care, with 14% running joint‐clinics with adult gastroenterologists. Transition services were not available in 28% of respondents’ institutions or run in as ad‐hoc manner (11%). The top barriers to successful transition were felt to be patient‐related (36%), parent‐related (27%), lack of interest or training in adult subspecialty colleagues (21%) and lack of handover between teams (17%).

Conclusions: This study provides real‐world data regarding transition services in paediatric gastroenterology in Asia‐Pacific region.In addition to well‐recognized patient‐related barriers, parent‐related factors were found to be significant. Programs developed for transition care in this region would need to take this into account. Joint clinics with adult providers were also identified as a need to be further developed in Asia‐Pacific region.

Contact e‐mail address: eesqin@gmail.com

LONG‐TERM TEDUGLUTIDE TREATMENT IN CHILDREN WITH SHORT BOWEL SYNDROME: A REAL‐LIFE, MULTICENTER, RETROSPECTIVE STUDY OF PATIENTS TREATED FOR MORE THAN 1 YEAR

Alessandro Molinaro¹, Esther Ramos Boluda², Cécile Lambe³, Anat Guz Mark⁴, Iva Hojsak⁵, Johannes Hilberath⁶, Ilse Broekaert⁷, Rocío González Sacristán², Antonella Lezo⁸, Paula Guerra⁹, Noel Peretti¹⁰, Arianna Ghirardi¹¹, Lorenzo D'Antiga¹, Lorenzo Norsa¹

¹Paediatric Hepatology Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy, Bergamo, Italy, ²Paediatric Intestinal Rehabilitation and Transplantation Unit, University Hospital La Paz, Madrid, Spain, ³Pediatric Gastroenterology And Nutrition Unit, Necker Enfants Malades Hospital, Paris, France, ⁴Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel, ⁵Children's Hospital Zagreb, Zagreb, Croatia, ⁶Paediatric Gastroenterology & Hepatology, University Children's Hospital Tübingen, Tübingen, Germany, ⁷Department Of Pediatrics, Division Of Gastroenterology, University of Cologne, Cologne, Germany, ⁸Dietetic and Clinical Nutrition Unit, Pediatric Hospital Regina Margherita, University of Turin, Turin, Italy, ⁹Paediatrics Department, Centro Hospitalar Universitário de São João, Porto, Portugal, Porto, Portugal, ¹⁰Hospices Civils de Lyon, Department of Pediatric Hepato‐Gastroenterology and Nutrition, Hôpital Femme Mere Enfant HFME, 59 Bd Pinel, 69677, Bron, France, Bron, France, ¹¹From Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy

Objectives and Study: Teduglutide, a GLP‐2 analog, effectively reduces the need for parenteral nutrition (PN) in managing short bowel syndrome‐associated intestinal failure (SBS‐IF) in children. This real‐life, multicenter, retrospective cohort study investigates the efficacy and safety of teduglutide in long‐term users.

Methods: The study enrolled 103 patients with SBS‐IF from the European Real‐TEDU Paediatric Registry across seven countries. The analysis focused on 69 patients who were treated with teduglutide for >1 year. Long‐term responders are defined as those achieving a reduction in PN >20% in volume/calories at the last follow‐up.

Results: Sixty‐nine patients with SBS‐IF, treated with 0.05 mg/kg/d teduglutide for more than one year (median follow‐up: 2.3 years), were included. The median time to response was 6.2 months. Long‐term responders constituted 64% (44/69).

Statistically significant differences in pre‐treatment data between non‐responders and long‐term responders were observed for the residual small bowel (median 20cm vs. 40cm, p=0.006) and total daily output (median 875ml vs. 1550ml, p=0.049).

When comparing long‐term responders with response at 1 year, 2/69 non‐responders at one year (5%) responded later on; 10/69 responders (14%) at 1 year subsequently lost their response. Furthermore, 24/69 children (34%) in our long‐term cohort were able to be weaned from PN support.

Out of 69 children, 26 (28%) experienced adverse events (AE), with 21/26 (81%) occurring in the first year of treatment. The total number of AEs was 54, including 25 severe adverse events, of which 7/25 appeared related to teduglutide treatment, 2/25 were life‐threatening and none resulted in death. There was no association between response and AE (p=0.76).

Conclusions: Long‐term teduglutide in children with SBS‐IF resulted in a sustained, and safe reduction in PN dependency. Further studies are required to evaluate the proportion of patients acquiring or losing response after one year, providing crucial insights into the durability and dynamics of teduglutide response over an extended period.

Contact e‐mail address: lnorsa@asst‐pg23.it

ESOPHAGEAL ATRESIA WITH TRACHEOESOPHAGEAL FISTULA IS ASSOCIATED WITH CONSANGUINITY

Raouf Nassar^1,2, Ohad Hougui³, Matan Zerem¹, Maha Omary¹, Zaki Assi^1,4, Galina Ling^1,2, Baruch Yerushalmi^1,2

¹Faculty Of Health Sciences, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel, Beer Sheva, Israel, ²Pediatric Gastroenterology Unit, Soroka Medical Center, Beer Sheva, Israel, ³Pediatrics Department A, Soroka University Medical Center Beer‐Sheva, Israel, Beer Sehva, Israel, ⁴Pediatric Surgery Department, Soroka University Medical Center Beer‐Sheva, Israel, Beer Sehva, Israel

Objectives and Study: Esophageal atresia with tracheoesophageal fistula (EA‐TEF) is a rare congenital malformation. The incidence of TEF is 1.3‐4.6 cases per 10,000 live births. The specific etiology of EA‐TEF is unknown. Environmental risk factors such as maternal use of medications and alcohol consumption during pregnancy are suggested. Genetic factors have also been described especially among the syndromic types such as VACTERL, CHARGE, and Down syndrome, but less among non‐syndromic types. The aim of the study is to examine the association between non‐syndromic EA‐TEF and consanguinity.

Methods: A retrospective study comparing the incidence of EA‐TEF between low‐consanguineous Jewish population and high‐consanguineous Bedouin population. All patients were treated at Soroka University Medical Center, the only tertiary medical center in southern Israel.

Results: During the years 2000‐2022, 579,130 children were born in southern Israel, 386,915 (67%) were Jewish, and 192,215 were Bedouin Muslims. A total of 96 patients were diagnosed with EA‐TEF, 83 of them were non‐syndromic EA‐TEF. The incidence of non‐syndromic EA‐TEF was 1.43 cases per 10,000 live‐births and was statistically higher among the Bedouin population (2.65 vs. 0.83 cases per 10,000 live‐births, P<0.001). The consanguinity rate among the Bedouin group was higher comparing with the Jewish (71% vs 0% P<0.001). There were no differences in other risk factors.

Conclusions: The incidence of EA‐TEF is exceptionally higher among the Bedouin population that live in the same geographic region and the same medical access as the Jewish population, proposing consanguinity as an important/essential risk factor of EA‐TEF.

Contact e‐mail address: Raouf.n@gmail.com

ESOPHAGEAL FOOD BOLUS IMPACTION IN PEDIATRIC AGE: A PROSPECTIVE ITALIAN COHORT STUDY

Maria Giovanna Puoti¹, Mariano Caldore¹, Antonia Pascarella¹, Sara Isoldi¹, Cristina Bucci¹, Piergiorgio Gragnaniello², Rosella Turco¹, Francesco Cirillo¹, Paolo Quitadamo¹

¹Paediatric Gastroenterology And Hepatology, Santobono‐Pausilipon Hospital, Naples, Italy, ²Scienze Mediche Traslazionali, Università degli studi Federico II di Napoli, Napoli, Italy

Objectives and Study: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in esophagus. Data regarding prevalence and underlying conditions of EFI in children is lacking. We aimed to investigate causes and characteristics of EFI referred to our Institution.

Methods: All paediatric patients (0‐16 years) admitted at the Emergency Department of Santobono‐Pausilipon Children's Hospital between March 2018 and March 2023 due to a first episode of EFI requiring endoscopic removal were prospectively enrolled. Demographic and clinical data including age, sex, signs and symptoms at admission, endoscopic and histological results were included. Two biopsies from each segment of oesophagus ‐ proximal, medium and distal ‐ and from any visible lesions were routinely obtained. Diagnosis of EoE was made if more than 15 eosinophils per high power field was demonstrated on esophageal mucosal biopsy.

Results: Over the study period 41 children were admitted for a first episode of food impaction (male 30, mean age 101.5±47.4 months). Most commonly reported symptoms were drooling (71%) and globus sensation (68%). Food bolus was stucked in the proximal esophagus in 15%, middle esophagus in 58% and distal esophagus in 27%. The most common diagnosis was EoE (49%). Anastomotic stricture at the level of oesophageal atresia repair was found in 10%. Other diagnosis were achalasia (1/41), esophageal duplication (1/41), peptic stricture (1/41), caustic stricture (1/41) and congenital stricture (1/41). In 29% of children no organic cause was found.

Conclusions: Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI in order to provide a complete diagnostic evaluation.

Contact e‐mail address: g.puoti@santobonopausilipon.it

EFFICACY OF ORAL VISCOUS BUDESONIDE TO REDUCE DILATION TREATMENT AFTER ESOPHAGEAL ATRESIA REPAIR: A RETROSPECTIVE STUDY

Cosimo Ruggiero¹, Giusy Russo¹, Denis Cozzi², Silvia Ceccanti², Chiara Scanziani¹, Danila Volpe¹, Paola Papoff³, Mattia Spatuzzo¹, Vasiliki Spyropoulou⁴, Salvatore Oliva¹

¹Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza, Rome, Italy, ²2. Pediatric Surgery Unit, Maternal and Child Health Department, Sapienza – University of Rome, Italy, Rome, Italy, ³Maternal and Child Health Department, Pediatric Intensive Care Unit, Sapienza, Rome, Italy, ⁴Division Of Pediatric Gastroenterology And Nutrition, University Children's Hospital Zurich, Zurich, Switzerland

Objectives and Study: Anastomotic stricture is a common complication following esophageal atresia (EA) repair, substantially affecting the patient's quality of life (QoL). Multiple dilations are often required to maintain the appropriate diameter of the esophagus, leading to ongoing challenges. The aim of this study is to assess the efficacy of oral viscous budesonide (OVB) in prolonging the time between symptom recurrence and subsequent dilation

Methods: We carried out a retrospective single‐center study, focusing on pediatric patients (0‐18 years) who had undergone recurrent esophageal dilations (≥3) following EA repair and started treatment with OVB (1 mg/day <10 years, otherwise 2 mg/day). Efficacy of topical steroid was determined by a dysphagia symptom score (DSS) ≤1 for at least 3 months. Recurrence time to dysphagia and dilation were analyzed according to Kaplan‐Meier method.

Results: Out of 29 patients initially screened, 19 were enrolled. All patients were responsive to OVB, and 13/19 (68%) did not required additional dilations. The median time between dilations was significantly prolonged compared to the pre‐treatment period [2 months vs 30 months; p<0.01] as well as the time to dysphagia relapse [1 month vs 18 months; p<0.01].

Conclusions: Topical budesonide has proven to be an effective treatment for recurrent esophageal stricture in repaired EA. However, further investigation is required to assess the long‐term sustained response of symptoms to topical steroids.

Contact e‐mail address: cosimo.ruggiero@uniroma1.it

SUCRASE‐ISOMALTASE GENE VARIANTS IN IRRITABLE BOWEL SYNDROME: IMPACT ON PROTEIN TRAFFICKING AND ENZYME FUNCTION

Stephanie Tannous¹, Mauro D'Amato², Hassan Y. Naim¹

¹Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany, ²LUM University, Casamassima BA, Italy

Objectives and Study: Sucrase‐isomaltase (SI) is the major intestinal brush border disaccharidase implicated in the final steps of carbohydrate digestion. Mutations in the SI gene elicit severe reduction or complete loss of catalytic activity and are thus associated with carbohydrate malabsorption, as described in congenital sucrase‐isomaltase deficiency (CSID). CSID is characterized by abdominal pain, flatulence, bloating, and acidic diarrhea. Another functional gastrointestinal disorder, irritable bowel syndrome (IBS), presents with symptoms overlapping with those of CSID. Recent studies have identified rare hypomorphic SI variants related to IBS risk in the UK Biobank. Here, we studied the intracellular trafficking and the function of SI variants predicted to be pathogenic.

Methods: COS‐1 cells were transiently transfected with cDNAs encoding wild‐type SI (SI^WT) or SI mutants (SI^Mutant). The trafficking behavior of SI^WT and SI^Mutant was assessed through alterations in the N‐glycosylation patterns towards endoglycosidase H (endo H) treatment. The cell surface digestive function of the variants was determined in cellular vesicles that retained their right‐side out cell surface orientation.

Results: Endo H‐treatment of SI^WT and various SI^Mutant could discriminate between the trafficking‐competent and ‐incompetent SI proteins. Several SI^Mutant exhibited an SI^WT‐like pattern of maturation, since they exit the ER and acquire endo H‐resistance compatible of complex glycosylation. Other SI^Mutant were entirely blocked in the ER due to their complete sensitivity to endo H. A third group of SI^Mutant was characterized by delayed trafficking between the ER and the Golgi. The enzyme function of the SI^Mutant exhibited wide variations not relevant to the trafficking phenotype. Thus, several normally trafficked mutants were enzymatically inactive or showed reduced function. The ER‐located SI^Mutant were entirely inactive, while slowly trafficked mutants were partially active.

Conclusions: Analysis of SI^Mutant demonstrated functional heterogeneities, some of which were compatible with their protein trafficking behavior that may allow a correlation with their corresponding pathogenicity scores and population prevalence.

Contact e‐mail address: stephanie.tannous@tiho‐hannover.de

STUDY OF THE MICROBIOTA IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) AND IN GRAFT‐VERSUS‐HOST DISEASE (GVHD) AND ITS IMPLICATIONS ON PROGNOSIS

Beatriz Vergara Muñoz¹, Laura Palomino Pérez², Marta Velasco Rodríguez‐Belvís², Carmen Herranz Sorribes³, Marianna Alejandra Di Campli Zaghlul², Carmen Martín Fernández⁴, Julio Alberto Vázquez Gómez², Claudio Alba Rubio³, Alberto Aragón⁵, Rubén Jurado⁵, Marta González Vicent¹, Blanca Molina Angulo¹, Jose Antonio Del Campo⁶, Paloma García Hernández², Almudena Muñoz González⁷, Elvira Cañedo Villarroya⁷, Agustín De La Mano Hernández⁷, Jorge Martínez Pérez⁷, Gloria Domínguez‐Ortega⁸, Nuria Puente Ubierna⁸, Paula Sánchez Llorente⁷, María Paz Manzanares¹, Lucia Becerro Méndez¹, Claudia Pina Pino¹, Beatriz Del Amo Mateos¹, Rosa Ana Muñoz Codoceo⁷

¹Onco‐hematology, Hospital Univesitario Niño Jesús, Madrid, Spain, ²Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, ³Nutrición Y Ciencia De Los Alimentos, Universidad Complutense de Madrid, Madrid, Spain, ⁴Hospital Univesitario Niño Jesús, Madrid, Spain, ⁵Farmacia Galénica Y Tecnología Alimentaria, Universidad Complutense de Madrid, Madrid, Spain, ⁶Clinical Analyses Department., Hospital Univesitario Niño Jesús, Madrid, Spain, ⁷Hospital Infantil Universitario Niño Jesús, Madrid, Spain, ⁸Gastroenterology And Nutrition Department, Niño Jesús University Children Hospital, Madrid, Spain

Objectives and Study: To characterize the clinical features, inflammatory markers, and microbiome of pediatric patients before and after HSCT.

Methods: Single‐center, observational, and prospective study of patients undergoing HSCT between October 2021 and March 2023 in a tertiary hospital. We analysed clinical characteristics, inflammatory parameters, and microbiome of the patients before transplantation, at the time of engraftment, at day +100 post‐transplantation and at the time of development of GVHD if this occurs.

Results:

Forty‐four patients were included (20 females, 24 males) with 70% having malignant and 30% non‐malignant hematological diseases. Of these, 65% received stem cells from a related donor, with 82% being non‐HLA identical, and 90% receiving graft‐versus‐host disease (GVHD) prophylaxis. Post‐HSCT, excluding GVHD, the crucial period for nutritional support needs (70%) and inflammatory marker elevation (IL‐6, TNF alpha, acid glycoprotein, and fecal calprotectin) and digestive symptoms (56%) occurred at engraftment. Higher plasma concentrations of IL‐8, IL‐6 and IFN‐gamma were significantly associated (p<0.05) with higher rates of GVHD. Additionally, IL‐6 was linked to higher mortality independent of GVHD occurrence (p<0.05). Relative abundance of Blautia, Streptococcus, Enterococcus, Enterococcus and Escherichia/Shigella species was observed pre‐GVHD. At the time of GVHD, there was a large decrease in the Blautia genus (0.02%), which was present in 100% at the pre‐GVHD time, with a significant increase in the median of Escherichia/Shigella sequences.

Conclusions: The study proposed potential prognostic markers, particularly the Blautia genus as a potential predictor of post‐HSCT outcomes. The results align with existing literature, indicating promising avenues for prognosis prediction, prevention, and treatment enhancement. Although further validation is necessary, the findings underscore the potential utility of microbiome analysis in understanding and managing complications post‐HSCT, particularly GVHD.

Contact e‐mail address: beatriz.vergara@salud.madrid.org

COLONIC MUCOSAL NEUROTRANSMITTER PROFILING REVEALS DISTINCT PATTERNS IN INDIVIDUALS WITH AUTISM SPECTRUM DISORDER, INFLAMMATORY BOWEL DISEASE AND THEIR CO‐OCCURRENCE AND RELATIONSHIP WITH THE MICROBIOME

Meng‐Che Wu^1,2, Rafail Kushak², Sarah Kadzielski², Emma Li³, Shyam Badu⁴, Qinglong Wu⁴, Tim Buie⁵, Tor Savidge⁴, Harland Winter²

¹Division Of Gastroenterology, Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan, ²Center for Pediatric Inflammatory Bowel Disease, MassGeneral Hospital for Children, Pediatric Gastroenterology, Hepatology and Nutrition, Boston, United States of America, ³Genetics Department, Kaiser Permanente South Bay, Los Angeles, United States of America, ⁴Department of Pathology & Immunology, Baylor College of Medicine, Houston, United States of America, ⁵Division of Pediatric Gastroenterology, Boston Children's Hospital, Boston, United States of America

Objectives and Study: Alterations in gut microbiota and neurotransmitters (NT) such as γ‐aminobutyric acid (GABA) and serotonin in the brain are associated with neurological disorders including autism. This study aimed to identify colonic mucosal‐associated microbes and NT in individuals with autism (ASD) and inflammatory bowel disease (IBD) that might improve understanding of the gut‐brain axis.

Methods: Colonic biopsies were collected from individuals with ASD, IBD, concurrent IBD and ASD (cIBD/ASD), and neurotypical controls without IBD (NTC). Mucosal biopsies were analyzed for NT (GABAergic, Serotonergic, Dopaminergic pathways) using mass spectrometry and the microbiome was assessed by shotgun metagenomics.

Results: 110 male patients (30 ASD, 30 IBD (with UC or CD), 20 cIBD/ASD and 30 NTC), mean age 17.4 years were enrolled. Differences in colonic mucosal NT levels were similar to previously reported CNS NT levels in ASD. However, in ASD, glutamate: GABA ratios were significantly elevated in colonic mucosa (1.7‐fold) compared with NTC, and this ratio was higher in individuals with cIBD/ASD. Intriguingly, diminished mucosal GABA levels were associated with an increased abundance of a marker for Evtepia gabavorous, a newly described GABA‐consuming bacterium. In addition, colonic mucosal serotonin levels were 3.5‐fold elevated in ASD compared with NTC; whereas, the highest concentrations of proinflammatory kynurenine and quinolinic acid were measured in subjects with IBD (IBD and cIBD/ASD).

Conclusions: These new findings highlight the potential significant interaction in the colonic mucosa between the microbiome and NT and the impact of the “gut‐brain” axis in the production and regulation of NT in individuals with ASD.

Contact e‐mail address: hwinter@mgh.harvard.edu

CALCIUM‐FORTIFIED ORAL REHYDRATION SOLUTION IS MORE EFFECTIVE THAN STANDARD ORAL REHYDRATION SOLUTION IN REDUCING DIARRHEA MORBIDITY IN CHOLERA TOXIN‐PRETREATED MICE

Sam Cheng

Department Of Pediatrics, University of Florida, Gainesville, United States of America

Objectives and Study: Diarrhea like cholera remains a leading cause of mortality and morbidity globally. Oral rehydration solution (ORS) significantly decreases diarrhea mortality; yet, it does not reduce diarrhea morbidity. Patients with diarrhea lose not only monovalent ions, which are replaced via ORS, but also divalent ions, which are not routinely replaced, particularly for Ca²⁺. Using in vitro technologies, we have previously shown that Ca²⁺, a primary ligand that activates the Ca²⁺‐sensing receptor (CaSR), can act on intestinal epithelium and enteric nervous system (ENS) and reverse cholera toxin‐induced fluid secretion. Here, we show that activating CaSR inhibits cholera toxin‐pretreated diarrhea in vivo.

Methods: CTX was given orally to C57BL/6 mice to induce diarrhea. Ca²⁺ and calcimimetic R568 were used to activate CaSR. To maximize their local intestinal actions, calcium was administered luminally via oral rehydration solution (ORS) whereas R568 applied serosally using an intraperitoneal route. To verify that their actions resulted from the intestine, effects were also examined on cre‐lox intestine‐specific CaSR knockouts. Diarrhea outcome was measured either biochemically through monitoring changes in fecal Cl^‐ or clinically by assessing stool consistency and weight losses.

Results: CTX induced secretory diarrhea, as evidenced by increases in fecal Cl^‐, stool consistency, and weight losses following CTX exposure, but did not alter CaSR, neither in content nor in function. Accordingly, Ca²⁺ and R568 were each able to ameliorate diarrhea when applied to diseased intestines. ORS supplemented with Ca²⁺ citrate, Ca²⁺ chloride or Ca²⁺ carbonate was more effective than standard ORS in reducing disease severity and duration. The intestinal CaSR involvement is suggested by gene‐knockout experiments where antidiarrheal actions of R568 in wild‐type mice were not observed in knockouts neither^villinCre/Casr^flox/flox lacking epithelial CaSR nor ^nestinCre/Casr^flox/flox lacking neuronal CaSR.

Conclusions: This study suggests that adding Ca²⁺ to ORS or using calcimimetic to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

Contact e‐mail address: sam.cheng@ufl.edu

SACCHAROMYCES BOULARDII COUNTERACTS OXIDATIVE STRESS INDUCED BY SARS‐COV‐2 IN HUMAN ENTEROCYTES

Valentina Cioffi, Marco Poeta, Chiara Fulgione, Giusy Arrichiello, Roberta Criscuolo, Andrea Lo Vecchio, Eugenia Bruzzese, Alfredo Guarino

Dipartimento Di Scienze Mediche Traslazionali, Università degli studi di Napoli Federico II, Napoli, Italy

Objectives and Study: SARS‐CoV‐2 is an enteric pathogen and the mechanisms of Covid‐associated diarrhea, are multiple, but in all the Spike protein plays a crucial role, acting as an enterotoxin able to induce chloride secretion in association with an increase in reactive oxygen species (ROS), with effects similar to NSP4 enterotoxin produced by rotavirus. Previous studies demonstrated the efficacy of selected probiotic strains, including Saccharomyces boulardii (Sb), against rotavirus‐associated diarrhea based on their antioxidant abilities. We therefore tested the antioxidant effects of Sb in an in vitro model of human enterocytes exposed to the Spike protein of SARS‐CoV‐2.

Methods: Oxidative stress was analyzed by standard assay assessing ROS levels (2,‐7,‐dichloro dihydrofluorescein, DCFDA) after Spike protein addition to Caco‐2 cell monolayers. The same experiments were performed after 1 hour of cell pre‐treatment with a post‐biotic preparation of Sb and after treatment with the toxic agent Sodium Arsenite (ARS) and the antioxidant compound N‐acetylcysteine (NAC), as positive and negative controls, respectively.

Results: Spike protein induced a significant 3‐fold increase in ROS production 15 minutes after stimulation (p<0.0001), with a toxic effect similar to ARS. Pre‐treatment with Sb prevented ROS production induced by Spike (p<0.0001) with a potency comparable to NAC. Also, the oxidative stress induced by ARS was prevented by cell treatment with Sb (p<0.0001). Sb prevents ROS production regardless of toxic stimulus.

Conclusions: In our experimental model, Sb prevented ROS production induced by the Spike protein exerting antioxidant abilities similar to NAC. The effect was observed using a conditioned medium without the living probiotic, suggesting that Sb produces antioxidant molecules implicated in the anti‐secretive effect, defining the so‐called postbiotic effect. Finally, this effect appears not dependent on the toxic stimulus as suggested by results of ARS experiments. Those results support the use of Sb in Covid‐associated diarrhea.

Contact e‐mail address:

OXIDATIVE STRESS AND LOCAL INFLAMMATION INDUCED BY SARS‐COV‐2 ON THE INTESTINAL MUCOSA

Marco Poeta¹, Mariantonia Maglio¹, Valentina Cioffi¹, Antonella Marano¹, Antonietta Tarallo¹, Carla Damiano¹, Roberto Peltrini², Valentina Discepolo¹, Alfredo Guarino¹

¹Department Of Translational Medical Science, Section Of Pediatrics, University of Naples Federico II, Naples, Italy, ²Department Of Public Health, University of Naples Federico II, Naples, Italy

Objectives and Study: SARS‐CoV‐2 is a virus with enteric tropism, causing gastrointestinal symptoms in up to 40% of patients. The Spike protein has a major role, acting as an enterotoxin and has been shown to induce ions secretion, with an oxidative stress dependent mechanism leading to the opening of a calcium activated chloride channel on apical surface of enterocytes. Aim of this study was to further explore the pro‐oxidant and pro‐inflammatory effects of SARS‐CoV‐2 on the intestinal epithelium, using both in vitro and ex vivo models.

Methods: Caco‐2 cells and stripped human colonic mucosa from surgical samples were exposed for 1 and 24 hours to SARS‐CoV‐2 (CoV2) or Spike protein alone. Chemokine CXCL10 levels were assessed by ELISA in Caco‐2 cell supernatants, while oxidative stress was analyzed by standard assays measuring ROS production (DCFH‐DA), GSH levels (DNTB), and lipid peroxidation (TBARS). Human colonic mucosa specimens were processed by immunohistochemistry to look at Ki67+ proliferating enterocytes within intestinal crypts and CD25+ infiltrating immune cells in the lamina propria.

Results: Both Spike protein and CoV2 preparation induced the secretion of CXCL10 after 24 hours (p<0.05) and short‐term promotion of oxidative stress, defined by a 2‐fold increase in ROS production and lipid peroxidation (p<0.005), and variations in glutathione levels (p<0.005) in Caco‐2 cells. In addition, human colonic mucosa exposed to Spike and CoV2 showed crypts proliferation in the colonic epithelium and an influx of activated CD25+ cells in the colonic lamina propria in response to Spike protein (p<0.005).

Conclusions: Both Spike protein and inactivated SARS‐CoV‐2 induce a first‐line host defence response to the viral trigger, promoting crypts proliferation and CXCL10 production. Furthermore, Spike protein promoted oxidative stress and an influx of inflammatory cells in the intestinal lamina propria without the need of viral entry and replication, suggesting further pro‐oxidant and pro‐inflammatory mechanisms in addition to the enterotoxic effect.

Contact e‐mail address:

ROLE OF BEE HONEY IN CHILDREN WITH FUNCTIONAL DYSPEPSIA

Mamdouh Abdulrhman, Amna Sayed, Yosra Awad

Pediatrics, Ain Shams University Children's hospital, Cairo, Egypt

Objectives and Study: Pharmacological intervention is unsuccessful in a significant number of functional dyspepsia cases. Honey is known to have antioxidant, and gastroprotective effects, but requires reevaluation as a potential treatment modality for functional dyspepsia. We aimed to assess the effects of honey on functional dyspepsia symptoms in children.

Methods: An open label randomized controlled clinical trial was conducted at a tertiary hospital with 65 children aged from 8‐18 years, diagnosed with functional dyspepsia, epigastric pain syndrome subtype, according to Rome IV criteria. Patients were randomly allocated into two groups: an intervention group (honey group) and control group. Both groups received proton pump inhibitors (PPIs) for 4 weeks, while the intervention group also received honey in addition to the PPIs. The PPIs were stopped after 4 weeks, while the intervention group continued to receive honey alone for another 4 weeks. The Modified Glasgow Dyspepsia Severity Score was used to assess the severity of dyspepsia. The primary endpoints were the patient responses at weeks 2, 4, 8, and 12 after randomization.

Results: The honey group showed a faster reduction in dyspepsia symptom scores at week 2 (4.55 ± 2.72) compared to the PPI only group (7.74 ± 1.91), with a significantly better cure rate at weeks 2 and 4 (15% and 78.8% in the honey group vs 0% and 54.8% in the control group respectively). Moreover, when patients continued to take honey alone for another 4 weeks, the symptom scores progressively decreased.

Conclusions: Honey administration did not worsen symptoms of functional dyspepsia, and it may even prove beneficial if further placebo‐controlled studies provide the evidence in this topic.

Contact e‐mail address: yosraawad@med.asu.edu.eg

ABDOMINAL ULTRASOUND TO DIAGNOSE FUNCTIONAL CONSTIPATION AND FECAL IMPACTION IN CHILDREN: A SYSTEMATIC REVIEW AND META‐ANALYSIS

Michelle Bloem¹, Johanna Vos¹, Anna De Geus¹, Desiree Baaleman¹, Ilan Koppen¹, Mariska Leeflang², René Spijker³, Marc Benninga¹

¹Emma's Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatric Gastroenterology and Nutrition, Amsterdam, Netherlands, ²Amsterdam UMC, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, University of Amsterdam, Amsterdam, Netherlands, ³Amsterdam UMC, Medical Library, University of Amsterdam, Amsterdam, Netherlands

Objectives and Study: Functional constipation (FC) is common in children. To date, no imaging test has proven to be valuable in diagnosing FC in children. The objective of this systematic review was to evaluate diagnostic accuracy of rectal diameter (RD) measurement via abdominal ultrasound in (1) diagnosing children with FC, and (2) identifying fecal impaction.

Methods: We included studies investigating diagnostic accuracy of measuring RD via abdominal ultrasound, in (1) children with and without FC according to the Rome II‐IV criteria, or (2) with and without fecal impaction determined by digital rectal examination. Data extraction and quality assessment, using QUADAS‐2, were performed. If possible, bivariate binomial regression meta‐analyses were performed to determine mean sensitivity and specificity.

Results: Sixteen studies were eligible for inclusion (n=1801 children, 0‐18 years old). Thirteen studies investigated the diagnostic accuracy of RD measurement in diagnosing FC, and five studies investigated the diagnostic accuracy of RD measurement in determining fecal impaction. Quality assessment revealed a high risk of bias across the majority of studies mainly due to un‐blinded case‐control designs. Cut‐off values to diagnose FC based on enlarged rectal diameters ranged from 2.4 to 3.8 cm. Seven studies (n=509) were included in the meta‐analysis to diagnose FC. Summary mean sensitivity and specificity estimates of RD measurement were 0.68 (95% CI 0.55‐0.78) and 0.81 (95% CI 0.71‐0.88), respectively. Due to high heterogeneity between studies, pooled analysis of studies examining the value of RD measurement in diagnosing fecal impaction was not feasible. Reported sensitivity and specificity values to diagnose fecal impaction (n=457) via RD measurement ranged between 68‐100% and 83‐100%, respectively.

Conclusions: Abdominal ultrasound can potentially be a valuable non‐invasive tool to diagnose FC by measuring RD and identifying fecal impaction in children. However, more research separating age groups to establish age‐dependent RD cut‐off values is needed to provide recommendations for its use in clinical practice.

Contact e‐mail address: m.n.bloem@amsterdamumc.nl

ESOPHAGEAL MOTILITY RECOVERY AFTER POEM IN CHILDREN WITH ACHALASIA

Giulia Chiarazzo¹, Paola De Angelis¹, Chiara Imondi¹, Filippo Torroni¹, Valerio Balassone², Renato Tambucci¹

¹Gastroenterology And Nutrition Unit, Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy, ²Digestive Endoscopy And Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

Objectives and Study: POEM (Peroral endoscopic myotomy) is demonstrating its potential as a definitive treatment option for pediatric esophageal achalasia (EA). Studies on adults have reported partial recovery of peristalsis in some patients with achalasia after POEM. Our study aims to investigate the impact of POEM on esophageal motility in the pediatric population.

Methods: We performed a retrospective study of children with EA who underwent POEM between 2016 and 2023. Only patients who performed high‐resolution esophageal manometry (HREM) before and after POEM were analyzed. HREM studies were reviewed according to Chicago Classification (CC) v4.0 and symptom severity was measured using the Eckardt score.

Results: A total of 15 EA patients (7 female, median age 12 years) were included. The initial diagnoses were 6 achalasia type I (40%), 8 type II (53.3 %) and 1 type III (6.6%). POEM resulted in an improvement in symptoms for all patients with a significant decrease in the Eckardt score (mean pre‐POEM 5.3 vs post‐POEM 0.53; p<0.001). Four patients (26.6%) with type II EA showed a partial recovery of esophageal peristalsis meeting the CC v4.0 criteria for ineffective esophageal motility. Absent peristalsis was observed in all other patients.

Conclusions: Pediatric achalasia can be effectively treated with POEM. It leads to partial recovery of esophageal peristalsis in over 20% of children with achalasia, all with type II. Further investigations are needed to assess the clinical implications of this finding.

Contact e‐mail address: giulia.chiarazzo@opbg.net

REPEATED AURICULAR PERCUTANEOUS ELECTRICAL NERVE FIELD STIMULATION (PENFS) IN PEDIATRIC PATIENTS WITH DISORDERS OF GUT‐BRAIN INTERACTION

Lev Dorfman¹, Kahleb Graham¹, Khalil El‐Chammas¹, Rashmi Sahay², Jennifer Hardy¹, Ajay Kaul¹, Neha Santucci¹

¹Division Of Gastroenterology, Hepatology, And Nutrition, Cincinnati Childrens Hospital Medical Center, Cincinnati, United States of America, ²Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

Objectives and Study: Percutaneous Electrical Nerve Field Stimulation (PENFS), a non‐pharmacological modality for treating pediatric disorders of gut‐brain interaction (DGBI) works by auricular stimulation of the cranial nerves supplying the gut. We examined the effect of repeated courses of PENFS on patients with recurrent symptoms and factors predicting the need for multiple rounds of treatment.

Methods: We evaluated charts of patients who underwent PENFS placement for DGBI in a single center. Data included: demographics, medical history, and validated questionnaire responses (see table 1). Changes in measures were compared over time with each round of placement. Baseline measures were compared between patients with single versus two rounds of PENFS.

Results: Seven patients [median age 18 years, all white females] underwent 2 PENFS treatment courses with an average interval of 10.6 months. An additional 211 patients underwent a single course [median age 16 years, 76% females, Table 1]. There was no significant difference in sex, age, race, and ethnicity between the groups. In the 7 patients with repeated PENFS Abdominal Pain Index, Nausea Severity Scale (NSS), Pain Catastrophizing Scale (PCS‐C), Functional Disability Inventory, Patient Health Questionnaire (PHQ‐9) and Children's Somatization Inventory (CSI) scores significantly reduced after the first course of treatment while PCS‐C, PHQ9 and non‐gastrointestinal CSI significantly reduced after the second course (p<0.05). Patients who underwent repeated PENFS treatment had significantly higher baseline NSS (2.99 vs. 2.08, p=0.0076) and PHQ‐9 (12.14 vs. 8.08, p=0.0496) scores. Rest of the measures did not differ between the two groups (p>0.05).

Conclusions: Repeating PENFS courses of treatment are becoming a standard of care in clinical practice. Worse nausea and psychological functioning may predispose to the need for multiple rounds of PENFS treatment. Further studies are needed to optimize the duration of treatment and strategies to sustain the response with PENFS.

Contact e‐mail address: levdorfman@gmail.com

ARE AIRWAY MICROBIOTA AND INFLAMMATION IN CHILDREN WITH ESOPHAGEAL ATRESIA RELATED TO REFLUX ASPIRATION?

Ranuli Dissanayake¹, Hannah Yuan¹, Michael Coffey^1,2, Isabelle Traini¹, Sin Yee Chan¹, Jessica Menzies³, Jennifer Hughes⁴, Isabelle Mckay¹, Josie Dorst¹, Steven Leach^1,2, Chee Y Ooi^1,2, Usha Krishnan^1,2

¹School Of Women's And Children's Health‐paediatrics, University of New South Wales, Randwick, Australia, ²Department Of Paediatric Gastroenterology, Sydney Children's Hospital, Randwick, Australia, ³Department Of Nutrition And Dietetics, Sydney Children's Hospital, Randwick, Australia, ⁴Department Of Speech Pathology, Sydney Children's Hospital, Randwick, Australia

Objectives and Study: This study aimed to assess the degree of airway dysbiosis and inflammation present in children with esophageal atresia (EA) compared to healthy controls (HC) and explore its association with reflux and respiratory outcomes.

Methods: This cross‐sectional study collected clinical data and oropharyngeal swabs from children with EA and HC. 16S rRNA gene sequencing (V4 region) was performed. Oropharyngeal S100A12 and pepsin levels were measured using enzyme linked immunosorbent assays. Targeted liquid chromatography mass spectrometry was utilized to measure bile acids. Associations between airway microbiota, inflammation, markers of reflux and respiratory outcomes were analyzed.

Results: Compared to age matched HC (n=44) samples, children with EA (n=44) had a lower mean bacterial richness of 96.7(SD 29.3) compared to the HC cohort, 121.3(SD 29.7) (p=2.8 × 10^‐7). The Shannon diversity index was significantly lower in the EA cohort, 2.47(SD 0.52), compared to the HC cohort, 2.80(SD 0.45) (p=0.001). Beta diversity analysis confirmed significant differences in bacterial composition between the two cohorts. Children with EA who experienced a chronic cough, had decreased richness, Shannon diversity and significant differences in beta diversity compared to children without a cough. Oropharyngeal S100A12 levels were higher in children with EA (n=30) compared to HC (n=30), 50.7 ng/ml (IQR 14.0 – 100.8) vs 14.7 ng/ml (IQR 7.8 ‐ 43.2), respectively (p=0.02). There was a positive correlation between pepsin and S100A12 levels in the EA cohort (r=0.38 p=0.04). Several bile acid concentrations including cholic, taurocholic, glycocholic, taurodeoxycholic and taurochenodeoxycholic acid, were significantly higher in children with EA (n=12) compared to HC (n=12). However, bile acid concentrations did not significantly correlate with pepsin or S100A12 levels.

Conclusions: Children with EA have an altered oropharyngeal microbiota and higher levels of inflammation compared to HC. Positive correlations of pepsin and S100A12 levels suggest a potential role of reflux in the development of airway inflammation in EA.

Contact e‐mail address: z5310652@ad.unsw.edu.au

PERORAL ENDOSCOPIC MYOTOMY (POEM) IN PEDIATRIC ACHALASIA: INSTITUTIONAL EXPERIENCE AND QUALITY OF LIFE

Carlijn Mussies¹, Thijs Kuipers², Aaltje Lei², Gwen Masclee², Paul Fockens², Barbera Bastiaansen², Marc Benninga³, Arjan Bredenoord², Michiel Van Wijk⁴

¹Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, ²Amsterdam Gastroenterology, Endocrinology And Metabolism, Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands, ³Pediatric Gastroenterology And Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, ⁴Pediatric Gastroenterology, Emma Children's Hospital ‐ Amsterdam Umc, Vrije Universiteit, Amsterdam, Netherlands

Objectives and Study: PerOral Endoscopic Myotomy (POEM) is currently a widely accepted treatment option for achalasia in adult patients. Studies evaluating safety and efficacy of POEM in children are scarce. No evidence is available on the effect of POEM on quality of life.

Methods: We performed a cohort study to evaluate effectiveness and safety of POEM in children with achalasia. Additionally, we prospectively compared quality of life of patients treated with POEM during their childhood to the results of a previous cohort study in our center evaluating the effect and quality of life of Pneumatic Dilation (PD) and Laparoscopic Heller's Myotomy (LHM) in children with achalasia.

Results: Thirty‐three achalasia patients (mean age at time of POEM 14.1(±2.5) years, 54.5% female; 12 (36.4%) type I, 19 (57.6%) type II, one (3.0%) type III, one (3.0%) unknown subtype) were included. Twenty‐nine (87.8%) had received previous treatment (PD(n=20); LHM(n=1); PD+ LHM(n=7); PD+Botox(n=1). POEM was technically successful in all patients and only minor intra‐operative events (bleeding n=3; mucosal perforation n=1) occurred. Mean follow‐up duration was 33(±25) months. Seventy percent did not need retreatment after POEM. Quality of life after POEM did not differ from the population norms. However, patients with an Eckardt score >3 had a significantly worse general (Kidscreen‐52: physical score 44.7 vs 52.4; p=0.011; mental score: 42.5 vs 51.3; p=0.038) and disease specific (35 vs 16; p=0.017) quality of life compared to those with an Eckardt ≤3. Overall, quality of life after POEM was not significantly different to PD and LHM. However, the SF‐36 mental health component score was significantly lower (44.2 vs 53.1; p=0.036) in patients treated with POEM compared to those treated with PD and LHM.

Conclusions: POEM is an effective and safe treatment for achalasia in children. Quality of life after POEM is largely comparable to the results obtained after PD and Heller.

Contact e‐mail address:

APP‐DELIVERED GUT‐DIRECTED HYPNOTHERAPY PROGRAM, NERVA, IMPROVES GASTROINTESTINAL SYMPTOMS AND PSYCHOLOGICAL OUTCOMES IN PEDIATRIC POPULATIONS: A RETROSPECTIVE AUDIT

Simone Peters, Peter Gibson, Emma Halmos

Monash University, Melbourne, Australia

Objectives and Study: App‐delivered gut‐directed hypnotherapy (GDH) improves physical symptoms and psychological outcomes in adult irritable bowel syndrome (IBS) populations. This retrospective audit aimed to assess the impact of app‐delivered GDH program, Nerva, in paediatric IBS patients.

Methods: Patients aged between 13‐18 years with self‐reported IBS were included for analysis. The app guided users through a 6‐week GDH program, consisting of daily hypnotherapy, psychoeducation, and breathing exercises. Gastrointestinal symptoms were assessed using a 100mm visual analogue scale, with a change of >30% on abdominal pain considered clinically relevant. Psychological outcomes were assessed at using the four‐item Patient Health Questionnaire for anxiety and depression (PHQ4).

Results: Data from 204 users were analysed. Most were female (72%), mean age 15.8 years, and had symptoms for 1‐5 years (48%). Abdominal pain decreased significantly from baseline 66 (95% CI 62‐70) mm to 46 (42‐50) mm at program completion (p<0.0001). Other gastrointestinal symptoms, including abdominal bloating, flatulence, dissatisfaction with stool consistency, and nausea also showed improvement. A total of 46% of patients experienced a >30% reduction in abdominal pain. Psychological outcomes improved, with a reduction in total PHQ4 scores from baseline (5.3; 95% CI 4.8‐5.9) to program completion (4.6; 4.1‐5.1) (p=0.011). Users with moderate and severe baseline PHQ4 scores showed greater improvements to their psychological state compared to the mild and normal categories. The percentage of users self‐reporting anxiety dropped from 57% at baseline to 43% at program completion, and depression decreased from 42% to 34%.

Conclusions: The app‐delivered GDH program, Nerva, significantly improves gastrointestinal symptoms and psychological outcomes in the majority of paediatric patients. It is particularly effective in improving outcomes for those with moderate and severe levels of anxiety and/or depression. These findings support the use of Nerva in paediatric populations and suggest the need for further research, including randomised controlled trials.

Contact e‐mail address: simone.peters@monash.edu

AUTONOMIC TESTING IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE AND IRRITABLE BOWEL SYNDROME: IN SEARCH OF DYSAUTONOMIA

Paola Ruška¹, Antonella Jerković¹, Sara Sila¹, Ana Pavic¹, Magdalena Krbot Skorić², Mario Habek^2,3, Iva Hojsak^1,3,4

¹Children's Hospital Zagreb, Zagreb, Croatia, ²University Hospital Center Zagreb, Zagreb, Croatia, ³University of Zagreb Medical School, Zagreb, Croatia, ⁴University of J.J: Strossmayer Medical School, Osijek, Croatia

Objectives and Study: The autonomic nervous system (ANS) is an important pathway connecting the brain and the gut. The aim of this study was to investigate the subjective and objective ANS abnormalities in children with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) compared to healthy controls (HC).

Methods: A total of 58 children were enrolled: 23 in IBS group (mean age 15 years, male n=7), 18 in IBD (mean age 14.25 years, male n=7) and 17 HC (mean age 14.83 years, male n=8). ANS symptoms were evaluated with the Composite Autonomic Symptom Score (COMPASS‐31). Heart rate (HR) and blood pressure (BP) responses to the Valsalva maneuver, HR response to deep breathing (RSA), BP response to passive tilt and quantitative sudomotor axon reflex test (QSART) were performed. The severity and distribution of ANS function was quantitated using adrenergic, cardiovagal and sudomotor indices of the Composite Autonomic Severity Scale (CASS).

Results: Children with IBS scored highest on the COMPASS 31, followed by patients with IBD and HC (median scores were 10.9, 5 and 1.6, respectively; p = 0.001). Moreover, children with IBS scored the highest on questions that involved various gastrointestinal symptoms, followed by children with IBD and HC. There was no significant difference between groups in CASS (p>0.05). However, there was a significant difference in symptomatic dysautonomia (defined as COMPASS‐31 > 7.913 and CASS >0) between children with IBS (56.5%) compared to children with IBD (38.9%) and HC (11.8%), p=0.015.

Conclusions: Symptomatic dysautonomia is most frequently observed in children with IBS, indicating an important contribution of ANS abnormalities to the pathophysiology of IBS. Founding: Croatian science foundation (IP‐2019‐04‐3028).

Contact e‐mail address: ivahojsak@gmail.com

RESTRICTIVE EATING IS ASSOCIATED WITH WORSE NAUSEA AND OTHER CLINICAL OUTCOMES IN CHILDREN AND ADOLESCENTS WITH DISORDERS OF GUT‐BRAIN INTERACTION

Hanson Ton¹, Jesse Li², Ausitn Vonaxelson³, Kahleb Graham^2,4, Rashmi Sahay⁵, Megan Miller^2,6, Emily Romantic⁷, Kathryn Hitchco*ck⁷, Neha Santucci^2,4

¹University of Cincinnati College of Medicine, Cincinnati, United States of America, ²Division Of Gastroenterology, Hepatology, And Nutrition, Cincinnati Childrens Hospital Medical Center, Cincinnati, United States of America, ³Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America, ⁴Pediatrics, University of Cincinnati College of Medicine, Cincinnati, United States of America, ⁵Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America, ⁶Behavioral Medicine And Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America, ⁷Nutrition Therapy, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

Objectives and Study: Disorders of gut‐brain interaction (DGBI) patients often restrict the amount and quality of food intake. We characterized nutritional deficiencies in DGBI patients and compared outcomes of patients with and without restrictive eating.

Methods: We reviewed the demographics, medical history, anthropometrics, nutritional disturbances, and responses to the following questionnaires: Abdominal Pain Index (API), Functional Disability Inventory (FDI), and Nausea Severity Scale (NSS) from charts of patients ages 6‐21y who met Rome 4 criteria for DGBI and compared them between those with and without restricted eating.

Results: Of 331 patients (mean age 15.6 y ± 2.6), 79% were female and 89% Caucasian, 92 % had abdominal pain, 73% nausea, 61% had anxiety, 32% depression and 4% had eating disorders. Sixteen % of patients had malnutrition [mild (10%), moderate (4%), and severe (2%)]. Eleven % were overweight and 20% obese. Fifty % had restricted eating, 23% received oral nutritional supplementation, and 9% required enteral tube feedings. Vitamin D deficiency was noted in 37% patients, iron deficiency anemia in 8%, vitamin A deficiency in 8%, and vitamin B12 deficiency in 4%. A registered dietitian saw 48% of patients with restricted eating. Nutritional supplementation was recommended in 14%, dietary treatment for 17%, probiotics for 13% and multivitamins for 7% of patients. DGBI patients with restricted eating had greater nausea scores (p = 0.006), rates of anxiety, depression, attention‐deficit/hyperactivity disorder (ADHD), sleep disturbances, and postural orthostatic tachycardia syndrome (POTS) as well as lesser weight, weight for age and body mass index Z scores than patients without restricted eating (p<0.05, Figure 1).

Conclusions: DGBI patients with restricted eating experience higher nausea, anxiety, depression, sleep disturbances, POTS, ADHD, and malnutrition. These findings highlight the importance of identifying restricted eating in DGBI patients and developing a multidisciplinary treatment approach.

Contact e‐mail address:

THERAPY DE‐ESCALATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN REMISSION – CHARACTERIZATION OF PHENOTYPE, TREATMENT, AND COURSE: DATA ANALYSIS FROM THE CEDATA REGISTRY

Sila Cekin¹, Ilse Broekaert¹, Christoph Huenseler¹, Hanna Gurmai², Jan De Laffolie³, Cedata Study Group²

¹Department Of Pediatrics, Division Of Gastroenterology, University of Cologne, Cologne, Germany, ²Department of General Pediatrics & Neonatology, Justus‐Liebig‐University, Gießen, Gießen, Germany, ³Department Of General Pediatrics & Neonatology, Justus‐Liebig‐University, Gießen, Gießen, Germany

Objectives and Study: Inflammatory bowel disease can be treated with different types of combination therapy (immunomodulator and biologic), but no standardized criteria about when, what and who to de‐escalate (stopping immunomodulator and/or biologic) exists. We aimed to describe how de‐escalation has been performed in the real world and to find prognostic factors for a successful de‐escalation.

Methods: Real‐world data from the CEDATA‐database, a large patient registry in Germany and Austria, from January 2004 to January 2023 were used to describe successful de‐escalation (no treatment intensification within 12 months after de‐escalation) in patients on combination therapy. Inclusion criteria are shown in figure 1. Statistical tests were used to find significant correlations between patient's baseline characteristics, clinical scores, treatment modalities, and successful de‐escalation.

Results: 230 out of 6248 registered patients received combination therapy for at least 6 months (figure 1). De‐ escalation was successful in 64 (28%) patients. The following differences in subgroups were found: Regarding differences between patients receiving combination therapy versus no combination therapy, Crohn's disease (CD) patients (p<0.001), younger patients (p<0,001), and patients with positive modified predictors of poor outcome (POPO) criteria (p<0.001) were more often on combination therapy. Regarding de‐escalation, CD patients were more often successfully de‐escalated than Ulcerative colitis (UC) patients (p=0.011). UC patients with less severe disease manifestation (Paris classification E1/2) were de‐ escalated more successfully than UC patients with more extensive disease (E3/4) (p=0.002). De‐escalation to monotherapy with a biologic led to a more successful de‐escalation than de‐escalation to immunomodulator monotherapy or stopping both biologic and immunomodulator (p<0.041).

Conclusions: As de‐escalation is more likely successful in patients with CD, and de‐escalating combination therapy to monotherapy with a biologic is more advantageous, these factors have to be considered in treating these patients on combination therapy, who have more often CD, are younger, and have more often positive modified POPO criteria.

Contact e‐mail address: sila.cekin@student.uni‐tuebingen.de

98 UNDERSTANDING ANTI‐TNF TREATMENT FAILURE IN CROHN'S DISEASE: MECHANISMS AND MANAGEMENT OF LOSS OF RESPONSE TO ANTI‐TNF THERAPY, THREE‐YEAR DATA FROM THE PANTS STUDY

Neil Chanchlani¹, Simeng Lin¹, Claire Bewshea¹, Benjamin Hamilton¹, Amanda Thomas¹, Rebecca Smith¹, Christopher Roberts¹, Maria Bishara¹, Rachel Nice¹, Charlie Lees², Shaji Sebastian³, Peter Irving⁴, Richard Russell⁵, Timothy Mcdonald¹, James Goodhand¹, Tariq Ahmad¹, Nicholas Kennedy¹

¹Exeter IBD Pharmacogenetics, Exeter, United Kingdom, ²Western General Hospital, NHS Lothian, Edinburgh, United Kingdom, ³Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom, ⁴Guy's and St Thomas’ NHS Foundation Trust, London, United Kingdom, ⁵Royal Hospital for Children & Young People, Edinburgh, United Kingdom

Objectives and Study: We report the effectiveness of infliximab (IFX) and adalimumab (ADAL) over the first three years of treatment, and define factors that predict anti‐TNF treatment failure and strategies that mitigate loss of response (LOR).

Methods: At the end of year 1 of PANTS, a UK‐wide, prospective cohort study, sites invited participants still receiving drug into the two‐year extension study. We estimate remission rates across the whole cohort, using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with LOR in anti‐TNF responders.

Results: 387/955 IFX‐ and 207/655 ADAL‐treated patients, 44% (96/219) paediatric patients aged 10 ‐ 17 years, who were recruited to PANTS entered the extension study. The estimated proportion of patients in remission at the end of year three was 34.7% (IFX) and 28.9% (ADAL). Optimal week 14 drug concentrations to predict remission at later timepoints were 6.1 ‐ 10 mg/L (IFX) and 10 ‐ 12 mg/L (ADAL). LOR events for IFX and ADAL‐treated patients were predicted by low anti‐TNF concentrations at week 14 (IFX: HR 0.43 for each 10‐fold increase in drug concentration, ADAL: HR 0.33). Drug‐clearing antibodies were detected in 44.0% (IFX) and 20.3% (ADAL) by year three. Treatment with an immunomodulator prior to, or at the time of, starting infliximab, was associated with increased survival without immunogenicity (Fig). The optimal thiopurine dose when used with IFX was >2.1 mg/kg azathioprine and >1.0 mg/kg mercaptopurine. Amongst IFX‐treated patients who were dose‐intensified at the point of LOR, those who experienced immune‐mediated pharmaco*kinetic failure had the lowest rates of drug persistence.

Conclusions: About one‐third of newly anti‐TNF treated patients with Crohn's disease are in remission at three years. LOR was predicted by low drug level. Drug‐clearing antibodies can be mitigated by an immunomodulator started prior to, or on the day of, the first infliximab infusion.

Contact e‐mail address: nchanchlani@doctors.org.uk

A SIGNIFICANT PUBLICATION BIAS EXISTS IN TRIALS OF BIOLOGICS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Ariel Weil¹, Gili Focht¹, Ohad Atia²

¹Juliet Keidan Institute Of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ²Juliet Keidan Institute Of Pediatric Gastroenterology, Hepatology And Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel

Objectives and Study: The use of biologic drugs in children with inflammatory bowel disease (IBD) sharply increased following the publications of positive results in randomized controlled trials and real‐world studies. We aimed to study the degree of publication bias associated with these results by exploring the publication rate of abstracts presented in conferences, and to explore the influence of “positive" results on the likelihood of publication.

Methods: Two reviewers reviewed all abstracts presented in the annual ESPGHAN and NASPGHAN conferences from 2015 to 2019. We included abstracts which evaluated the effectiveness or safety of biologics. “Positive" results were defined as those in the direction towards the primary outcome, even without statistically significant. Time to publication was explore by Kaplan‐Meier curve and the groups were compared by the log‐rank test.

Results: Of abstracts reviewed, 209 were included (115 [55%] from ESPGHAN and 94 [45%] from NASPGHAN conferences), of which only 130 (62%) were eventually published as a full manuscript. The median time to publication was 2.8 years (IQR 0‐8.2). The likelihood of publication was seven times higher for abstracts reporting positive results (120/170 [71%] vs. 10/40 [25%]; OR 7.1 [95%CI 3.2‐15.5], p<0.001). Similarly, the probabilities for publication after 6, 12 and 24 months were 20%, 32% and 49% for abstracts with positive results compared to 5%, 10% and 12% for negative results (p<0.001; Figure). In Cox regression multivariable model adjusted to various variables, positive results was the only significant factor for future publication (OR 6.5 [95%CI 2.6‐16.7]).

Conclusions: Only 62% of abstracts presented in medical conferences regarding biologics in pediatric IBD are eventually published as full text, and abstracts with positive results were much more likely to be published and at earlier time. Clinicians need to be aware of potential publication bias of published studies when employing evidence‐based management strategies.

Contact e‐mail address: ohadatia89@gmail.com

TRANSITION SUCCESS SCORE AS A VALID QUANTITATIVE MEASURE TO EVALUATE THE EFFECT OF TRANSITIONAL CARE IN IBD PATIENTS

Martha Gaalen¹, Merel Pieterson¹, Lissy De Ridder¹, Lauranne Derikx², Hankje Escher¹

¹Paediatric Gastroenterology, Erasmus MC‐ Sophia children's hospital, Rotterdam, Netherlands, ²Gastroenterology, Erasmus MC, Rotterdam, Netherlands

Objectives and Study: Transition programs are designed to prepare adolescent with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way. The aim of this study was to develop and validate a quantitative Transition Success Score (TSS) by the identified key components of successful transition.

Methods: TSS was developed through an international Delphi study, with pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. After four rounds of discussion a consensus was reached on the initial version of the TSS. This score includes seven items for adult healthcare providers to evaluate the patient's disease management behavior. Additionally, two items concern patient and parent experience concerning the transition period.

TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients in the Netherlands.

Results: In seven hospitals, 160 IBD patients (median age 19.05) completed TSS, at 9‐15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant presence of characteristics related to transitional care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=<0.005). In addition, Rasch analysis for structural validation showed that TSS was discriminating at lower levels of transition success. Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either “laid back, nonchalant” or “worried and uncertain”.

Conclusions: The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care and for measuring the effect of various transition programs in IBD.

Contact e‐mail address: m.vangaalen@erasmusmc.nl

INFLAMMATORY BOWEL DISEASE TYPE UNCLASSIFIED IN PAEDIATRIC‐ONSET IBD: A NATIONWIDE COHORT STUDY WITH UP TO 20 YEARS FOLLOW‐UP

Laura Gianolio¹, David If Wands^1,2,3, Fiona Cameron⁴, Richard Hansen⁵, Richard Russell^1,2, David C. Wilson^1,2

¹Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom, ²Child Life and Health, Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom, ³Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, United Kingdom, ⁴Department of Paediatric Gastroenterology, Hepatology and Nutrition, Alder Hey Children's Hospital, Liverpool, United Kingdom, ⁵Child Health, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom

Objectives and Study: Given the paucity of long‐term longitudinal data for inflammatory bowel disease type unclassified (IBDU) we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years follow‐up.

Methods: We analysed a prospectively identified 11‐year cohort of IBDU patients diagnosed 01/01/03‐31/12/13 via all Scottish paediatric IBD centres and followed‐up into adult‐services until 01/01/23. All had an IBDU diagnosis based on Porto criteria. Follow‐up data were obtained from electronic medical records (demographics, diagnostic plus repeat endoscopic and radiological assessments, longitudinal disease severity based on global clinician assessment, medical treatment and surgical outcomes) at fixed time points (5‐ and 10‐years post‐diagnosis) and at the last follow‐up.

Results: Overall, 116 patients were initially identified as IBDU, with 14 excluded as emigrated out of area before the first time point. 102 patients were finally included (57/102 (56%) male, median age 11.5 (IQR:9.1‐13.2) years) with a median follow‐up length of 10.5 (IQR:8.6‐14.0) years. A change of diagnosis was made in 61/102 (60%) patients with 30/102 (29%) reclassified as Crohn's disease (CD) and 31/102 (30%) as ulcerative colitis (UC) after a median disease duration of 5.0 (IQR:2.0‐8.2) and 4.7 (IQR:1.8–7.7) years, respectively (Figure1A). Patients who remained IBDU had a milder disease course with higher 1–5‐year remission rates (IBDU 30/39 (77%) vs CD/UC‐reclassified 16/57 (28%), p<0.05), lower rates of moderate‐to‐severe disease (IBDU 3/39 (8%) vs CD/UC‐reclassified 31/57 (54%), p<0.05‐Figure1B), less need for biologics across all time points (all p<0.05) and a higher proportion managed on aminosalicylates/no‐medication (all p<0.05). Higher rates of surgical resections were observed in CD/UC‐reclassified (IBDU 1/41 (2%) vs CD/UC‐reclassified 11/61 (18%), p=0.02).

Conclusions: In our nationwide paediatric IBDU cohort 60% of patients were reclassified as either UC or CD over 10.5 years of median follow‐up; those who remained IBDU had a milder disease course and decreased need of biologics.

Contact e‐mail address: david.wands4@ggc.scot.nhs.uk

EARLY PROACTIVE THERAPEUTIC DRUG MONITORING WITH USTEKINUMAB THERAPY IN PAEDIATRIC CROHN'S DISEASE

Amanda Ricciuto¹, Hayley Mckay², Jennifer Debruyn³, Eileen Crowley⁴, Peter Church¹, Hien Huynh⁵, Anthony Otley⁶, Ayub Shaikh¹, Wael El‐Matary⁷, Eytan Wine⁵, Thomas Walters¹, Anne Griffiths¹

¹Division Of Gastroenterology Hepatology And Nutrition, The Hospital for Sick Children, Toronto, Canada, ²The Hospital for Sick Children, Toronto, Canada, ³University of Calgary, Calgary, Canada, ⁴London Health Sciences Centre, London, Canada, ⁵Stollery Children's Hospital, Edmonton, Canada, ⁶IWK Health Centre, Halifax, Canada, ⁷University of Manitoba, Winnipeg, Canada

Objectives and Study: We aimed to examine real‐world post‐induction ustekinumab (UST) pharmaco*kinetic and effectiveness in a prospective multicentre paediatric CD cohort.

Methods: Luminal CD patients 2‐17y were eligible if they received UST IV and had a proactive week (wk) 8 serum UST level measured. UST levels were compared between children <40 and ≥40 kg. We calculated a “dose to exposure ratio” by dividing induction dose by wk8 level. Clinical remission was defined as wPCDAI <12.5. We used ROC curves to define optimal (Youden) wk8 levels associated with wk16 remission and UST continuation. Continuous measures are reported as median (IQR).

Results: 44 children were eligible (70% M; 13.1 (10.8‐15.5) y; disease duration 0.3 (0.08‐1.3) y; weight 44.7 (30.4‐55.0) kg, 75% bio‐naïve). At UST start, wPCDAI was 27.5 (10‐52.5) and albumin similar between weight groups (p=0.3). 68% received 260 mg IV loading, 16% 390 mg. Induction doses in mg/kg and mg/m² were significantly higher in children <40 kg (Figure1). Despite this, wk8 (and subsequent) levels were similar between weight groups.

The dose (mg/kg) to exposure ratio was 1.45x higher in children <40kg. Interval shortening to q4wk occurred in 7 before wk16, and in 16 (36%) by 6 months. By wk16, 56% with available wPCDAI were in clinical remission and 60% at 1 year. Overall, 7 (16%) ceased UST. Wk8 UST levels were numerically higher in patients achieving wk16 clinical remission (7.4 (6.2‐10.2) vs. 5.5 (2.6‐7.1), p=0.094), and lower in patients ceasing UST (4.9 (2.6‐6.9) vs. 7.3 (5.4‐10.7), p=0.087). Optimal wk8 UST level for wk16 clinical remission was 5.8 (AUC 0.68, sensitivity 78%, specificity 57%). Optimal level for UST continuation was 7.9 (AUC 0.73, sensitivity 43%, specificity 100%).

Conclusions: Paediatric CD patients <40kg required higher UST doses for comparable drug exposure. Positive clinical outcomes were associated with higher UST levels (with optimal cut‐offs 6‐8).

Contact e‐mail address: amanda.ricciuto@sickkids.ca

THE FEASIBILITY AND SAFETY OF SMALL BOWEL CAPSULE ENDOSCOPY IN VERY EARLY‐ONSET INFLAMMATORY BOWEL DISEASE: A MULTI‐INSTITUTIONAL STUDY

Shin‐Ichiro Hagiwara¹, Hirotaka Shimizu², Ryusuke Nambu³, Keisuke Jimbo⁴, Emiri Kaji⁵, Takuya Nishizawa⁶, Fumihiko Kakuta⁷, Itaru Iwama³, Takahiro Kudo⁴, Takashi Ishige⁶, Katsuhiro Arai²

¹Department Of Gastroenterology, Nutrition And Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan, ²Division Of Gastroenterology, Center For Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan, ³Division Of Gastroenterology And Hepatology, Saitama Children's Medical Center, Saitama, Japan, ⁴Department Of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan, ⁵Department Of Pediatrics, Osaka Medical and Pharmaceutical University, Osaka, Japan, ⁶Department Of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan, ⁷Department Of Gastroenterology, Miyagi Children's Hospital, Miyagi, Japan

Objectives and Study: The revised Porto criteria recommend small bowel capsule endoscopy (SBCE) or magnetic resonance enterocolonography for small bowel observation when typical ulcerative colitis (UC) cannot be diagnosed. However, there is no evidence for SBCE for very early‐onset inflammatory bowel disease (VEO‐IBD) that developed under the age of 6 years old. The aim of this study is to study the feasibility and safety of SBCE in VEO‐IBD.

Methods: The participants were patients with VEO‐IBD who underwent SBCE between January 2013 and December 2022 at six Japanese pediatric IBD centers. Age at the time of SBCE was less than 6 years. Medical records were used to conduct a retrospective study, and certified pediatric gastroenterologists at each institution diagnosed the small bowel findings.

Results: Eighty‐five patients (46 men; 21 cases were UC, 26 were Crohn's disease [CD], 37 were IBD‐unclassified [IBD‐U], and 1 was intestinal BD) were enrolled, and 104 procedures (median age 3.8 years, median weight 13 kg) were analyzed. All SBCE were placed endoscopically, and in 99 cases (95.2%), delivery device was used. Of the 39 patients who underwent SBCE alone, magnesium citrate was most commonly used for bowel preparation in 28 patients (71.8%). Of the 99 cases (95.2%) in which gastrointestinal (GI) patency was evaluated, patency capsules were used in 70 cases. Ultrasound was the second most commonly used modality to ensure GI patency (22 cases [22.2%]). Ninety‐eight cases (94.2%) had the entire small intestine observable, with a positive finding rate of 44.2%, and with aphthae being the most common (36.5%), followed by ulcers (17.3%). No serious complication including retention was reported, and only one case experienced difficulty in excreting the capsule from the rectum.

Conclusions: In this study, SBCE for VEO‐IBD could be performed safely with no retention. Therefore, the protocol of SBCE for VEO‐IBD is warranted.

Contact e‐mail address: hagi114@wch.opho.jp

IS DIVERSITY IMPORTANT IN THE GUT MICROBIOME AT IBD ONSET? A SYSTEMATIC REVIEW OF THE LITERATURE AND META‐ANALYSIS OF ALPHA‐DIVERSITY DATA

Peter Rimmer¹, Gregor Scott², Nabil Quraishi³, Karl Hazel³, Rachel Cooney³, Fan Zhang⁴, Georgina Hold⁴, Morris Gordon⁵, Tariq Iqbal¹, Richard Hansen⁶

¹Institute Of Immunology And Immunotherapy, University of Birmingham, Birmingham, United Kingdom, ²Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom, ³Gastroenterology, Birmingham NHS Foundation Trust, Birmingham, United Kingdom, ⁴Microbiome Treatment Centre, University of New South Wales, Sydney, Australia, ⁵University of Central Lancashire, Preston, United Kingdom, ⁶Division Of Clinical And Molecular Medicine, University of Dundee, Dundee, United Kingdom

Objectives and Study: Disruption of the microbiome is widely reported in inflammatory bowel disease (IBD), particularly a reduction in bacterial diversity. Understanding how this contributes to IBD pathogenesis requires research on newly‐diagnosed patients. We present a systematic review of the bacterial microbiome in new‐onset/treatment‐naive IBD.

Methods: We searched MEDLINE/Embase between inception and December 2022 for any study presenting bacterial microbial analysis of new‐onset/treatment‐naive IBD. Screening/extractions were performed independently in duplicate. Data extracted included all measures of microbial diversity, the source of samples, reported controls and clinical/patient parameters. We performed random‐effects meta‐analysis of standardised mean difference, reporting 95% confidence interval sub‐grouped by IBD type.

Results: 10,804 abstracts were screened. The study PRISMA is shown in Figure 1A. 91 studies were included. 11 diversity indices were used. 20 studies presented alpha diversity indices utilising high‐throughput sequencing from IBD and controls, 90% offered a Shannon index. This was therefore used for synthesis, including: faecal samples from 405 IBD (116 mixed, 225 Crohn's disease [CD], 64 ulcerative colitis [UC]), 324 healthy controls (HC) and mucosal biopsies from 171 CD with 172 symptomatic controls (SC) and 32 UC with 47 SC. The majority of studies (67%) were paediatric. Shannon diversity in faeces was significantly lower in IBD compared to HC, across both UC and CD (12 studies‐ Figure 1B). Shannon diversity was not significantly different in mucosal biopsies in either CD (7 studies, Figure 1C) or UC (3 studies, Figure 1D) against SC.

Conclusions: In new‐onset/treatment‐naive IBD, alpha diversity by Shannon index is significantly reduced in faecal samples in all IBD, CD and UC against HC but not in mucosal biopsies in CD or UC against SC. Faecal microbial diversity in IBD may perhaps be influenced by confounders such as rapid transit and malabsorption. Furthermore, the similar mucosal diversity in IBD and SC may suggest "dysbiosis" in functional gastrointestinal disease.

Contact e‐mail address: rhansen002@dundee.ac.uk

PINPOINT: THE PROSPECTIVE EPIDEMIOLOGY OF PAEDIATRIC‐ONSET INFLAMMATORY BOWEL DISEASE IN THE UK – A PROSPECTIVE, NATIONAL, COHORT STUDY

Paul Henderson^1,2, Liz Dobson³, Ibd Registry³, Pinpoint Collaborators²

¹Royal Hospital for Children and Young People, Edinburgh, United Kingdom, ²Child Life And Health, University of Edinburgh, Edinburgh, United Kingdom, ³Senior Management, IBD Registry Ltd, London, United Kingdom

Objectives and Study: Paediatric inflammatory bowel disease (PIBD) incidence and prevalence is increasing worldwide. The last prospective United Kingdom (UK) PIBD incidence study was performed in 1999 (5.2/100,000/yr); we aimed to update this incidence data and to provide a robust prevalence figure for PIBD prospectively across the UK.

Methods: Robust site selection identified all units in the UK providing endoscopy services for paediatric patients. Patients were included if they were diagnosed with Crohn's disease (CD), ulcerative colitis (UC) or IBD‐unclassified (IBD‐U) less than 16yrs of age. Basic demographics were recorded prospectively from June 2021 – December 2022 (18 months). Point prevalence on 28.02.23 was also performed. Some patients were also approached to provide consent for future research (the PINPOINT cohort). Data was securely collated by the IBD Registry and basic descriptive statistics performed in R v4.1.3. Publicly available population data was used to calculate rates.

Results: 34 sites prospectively recorded cases; all were diagnosed by ileocolonoscopy. There were 2,243 new diagnoses (1,050 [47%] consented to the PINPOINT cohort). UK PIBD incidence was 12.1/100,000/yr (England/Wales 11.7/100,000/yr, Northern Ireland 12.7/100,000/yr, Scotland 17.2/1000,000/yr). CD (56%) was more prevalent than UC (33%) and IBDU (11%). Median age at diagnosis was 12.9yrs (IQR 10.6‐14.5). There was a male preponderance (62%) with CD, IBDU and UC having male to female ratios of 1.8, 1.7 and 1.4 respectively. 72% of patients identified as white; those of other ethnicities were diagnosed younger (12.1yrs vs 13.0yrs; p<0.001) and had a higher incidence of UC (38.5% vs 30.3%; p=0.003). 6,116 patients were identified as living with IBD in Feb 2023 giving a UK prevalence of 49.6/100,000 (England/Wales 48.7/100,000, Northern Ireland 53.3/100,000, Scotland 58.6/1000,000).

Conclusions: There has been over a two‐fold rise in PIBD incidence in the UK since 1999. Further analysis of epidemiological trends using these data and the PINPOINT cohort are merited to drive improved care.

Contact e‐mail address: paul.henderson@nhslothian.scot.nhs.uk

TREATMENT OF ACTIVE CROHN'S DISEASE WITH EXCLUSIVE ENTERAL NUTRITION DIMINISHES THE IMMUNOSTIMULATORY POTENTIAL OF FECAL MICROBIAL PRODUCTS

Caroline Kerbiriou¹, Caitlin Dickson¹, Ben Nichols¹, Michael Logan¹, Anna Mascellani², Jaroslav Havlik², Richard Russell³, Richard Hansen^4,5, Simon Milling⁶, Konstantinos Gerasimidis⁷

¹Human Nutrition, School Of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, United Kingdom, ²Department Of Food Science, Czech University of Life Sciences Prague, Prague, Czech Republic, ³Department of Paediatric Gastroenterology, Royal Hospital for Children and Young People, Edinburgh, United Kingdom, ⁴Paediatric Gastroenterology, Hepatology And Nutrition, Royal Hospital for children, Glasgow, United Kingdom, ⁵Department Of Child Health, Division Of Clinical And Molecular Medicine, School Of Medicine, University of Dundee, Dundee, United Kingdom, ⁶School Of Infection And Immunity, University of Glasgow, Glasgow, United Kingdom, ⁷Human Nutrition, University of Glasgow, Glasgow, United Kingdom

Objectives and Study: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immuno‐stimulatory potential of a cell‐free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.

Methods: Production of TNFα from peripheral blood mononuclear cells was measured following their stimulation with cell‐free fecal slurries from children with CD, before, during and at completion of EEN. The metabolomic profile of the feces used was quantified using ¹H NMR and their microbiota composition with 16S rRNA sequencing.

Results: Following treatment with EEN, 8 of 11 (72%) patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labelled FC responders. In this subgroup, TNFα production from PBMCs was reduced during EEN (p=0.008) and reached levels like healthy controls. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p‐cresol significantly increased. At EEN completion, TNFα production from PBMCs was positively correlated with butyrate (rho=0.70; p=0.016). Microbiota structure (β‐diversity) was influenced by EEN treatment and a total of 28 microbial taxa changed significantly in FC responders. At EEN completion, TNFα production positively correlated with the abundance of fibre‐fermenters from Lachnospiraceae_UCG‐004, and Faecalibacterium prausnitzii, and negatively with Hungatella and Eisenbergiella tayi.

Conclusions: This study offers proof‐of concept data to suggest that the efficacy of EEN may result from modulation of diet‐dependent microbes and their products that cause inflammation in patients with CD.

Contact e‐mail address: Konstantinos.gerasimidis@glasgow.ac.uk

THE ASSOCIATION OF INFLAMMATORY BOWEL DISEASES WITH FAMILIAL MEDITERRANEAN FEVER: A NATIONWIDE STUDY FROM THE EPI‐IIRN

Michal Kori¹, Ofra Goldzweig², Rachel Buchok³, Yiska Loewenberg Weisband⁴, Noa Tal⁵, Shira Greenfeld⁶, Amir Ben Tov⁶, Natan Ledderman⁷, Eran Matz⁸, Iris Dotan⁹, Dan Turner³, Dror Shouval⁵

¹Pediatric Gastroentrology, Kaplan Medical Center, Rehovot, Israel, ²Pediatric Rheumatology, Kaplan Medical center, Rehovot, Israel, ³Juliet Keidan Institute Of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ⁴Clalit Health Services,, Tel‐ Aviv, Israel, ⁵Institute Of Gastroenterology, Nutrition And Liver Diseases,, Schneider Children's Medical Center, Petah Tikva, Israel, ⁶Maccabi Health Services, Tel Aviv, Israel, ⁷Meuhedet Health Services, Tel Aviv, Israel, ⁸Leumit Health Services, Tel‐ Aviv, Israel, ⁹Division Of Gastroenterology, Rabin Medical Center, Rabin Medical Center, Petah Tikva, Israel

Objectives and Study: Inflammatory Bowel Diseases (IBD) and Familial Mediterranean Fever (FMF) are auto‐inflammatory diseases with common clinical, genetic and biological features. We aimed to determine the association between IBD and FMF and to characterize the natural history in patients with both diseases.

Methods: We utilized health administrative data collected from all four health maintenance organizations (HMOs) in Israel, covering 98% of the population. The prevalence of FMF was compared between IBD patients versus non‐IBD controls, matched by sex, year of birth, district and HMO. Case ascertainment of IBD was determined according to validated electronic algorithms and for FMF by relavant ICD‐9 codes and Colchicine purchases. Outcomes included IBD treatment escalation, time to surgery or death.

Results: In total, 34,375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared to 93,602 non‐IBD controls. Of the IBD patients, 157 (0.5%) had FMF compared with 160 (0.2%) of controls (OR = 2.68 [95% CI 2.2‐3.3]; p<0.001). Pediatric‐onset IBD patients had a higher prevalence of FMF compared to adult‐onset IBD (30/5,243 [0.57%] vs. 127/29,132 [0.43%], (OR=6.14 [95% CI 3.1‐12.4]); p < 0.001), CD patients had a higher prevalence of FMF compared to UC (114/19,264 [0.6%] vs. 43/15,111 [0.3%]; OR=2.1 [95% CI 1.5–3.0]), p<0.001). The diagnosis of FMF preceded the diagnosis of IBD in 130 of the 157 cases (83%). There were no differences in disease severity at time of IBD diagnosis between patients with or without concurrent FMF and IBD disease outcomes were comparable between these groups.

Conclusions: FMF is more prevalent in IBD patients than in the general population, especially in children and in CD, but does not seem to affect the course of IBD.

Contact e‐mail address: korifamily@yahoo.com

DURABILITY OF ANTIBODY RESPONSES TO SARS‐COV‐2 VACCINE OVER 12 MONTHS IN PATIENTS WITH PAEDIATRIC INFLAMMATORY BOWEL DISEASE

Sally Lawrence, Marina Viñeta Paramo, Frederic Reicherz, Zahra Jama Hussein Shire, Liam Golding, Pascal Lavoie, Kevan Jacobson

BC Children's Hospital, University of British Columbia, BC, Canada, Vancouver, Canada

Objectives and Study: The long‐term effects of paediatric inflammatory bowel disease (PIBD) therapies on immune responses to SARS‐CoV‐2 vaccination are unknown. We aimed to determine the durability of SARS‐CoV‐2 vaccine‐induced responses over 12 months in immunosuppressed PIBD patients

Methods: In this prospective cohort study of PIBD patients aged 5‐18 years, anti‐spike antibody responses were measured at 1, 3, 6 and 12 months after the first SARS‐CoV‐2 vaccination. The primary outcome was to evaluate immunogenicity of SARS‐CoV‐2 vaccination over 12 months after the first vaccine in patients treated with anti‐tumor necrosis factor alpha (TNF) therapies with or without an immunomodulator (IM) compared to vedolizumab.

Results: Between 01.06.21 and 01.06.22, 194 participants were recruited including patients on anti‐TNF monotherapy (n=78), anti‐TNF with an IM (n=83), vedolizumab (n=15) and steroids (n=18). Serological analysis post‐vaccination showed increasing trends in anti‐SARS‐CoV‐2 Spike IgG titers after the first vaccine dose in all participants. Antibody titers were further boosted 1 month after the second dose. Responses were sustained over time, with minor antibody decay (‐0.02 per week [95%CI: ‐0.03 ‐ ‐0.01, p<0.001]) counterbalanced by the administration of booster doses (1.13 AU/mL per additional vaccine dose [95%CI: 1.01 ‐ 1.21, p<0.001]) [Figure 1]. Multivariable modelling showed anti‐TNF therapy with or without an IM contributed to reduced antibody responses compared to vedolizumab (p=0.001 and 0.007 respectively). Additional vaccine doses and SARS‐CoV‐2 infection contributed to higher antibody responses. There was no difference in seroconversion rates between cohorts. Breakthrough infection rates were similar between groups and infections were mild without hospitalizations.

Conclusions: Although we report an attenuated antibody response for patients on anti‐TNF with or without IM compared with those on vedolizumab this did not impact protection as seroconversion and breakthrough infection rates were similar between cohorts with no hospitalizations. Additional vaccine doses promoted increased antibody levels highlighting the importance of vaccine optimization for immunosuppressed PIBD patients.

Contact e‐mail address: sally.lawrence@cw.bc.ca

MATERNAL INFECTIONS AND USE OF ANTIBIOTICS DURING PREGNANCY AND OFFSPRING RISK OF INFLAMMATORY BOWEL DISEASE: PRELIMINARY RESULTS FROM TWO SCANDINAVIAN BIRTH COHORTS

Annie Guo¹, Johnny Ludvigsson^2,3, Tereza Lerchova¹, Henrik Imberg⁴, Ketil Stordal^5,6, Karl Mårild^1,7

¹Department Of Pediatrics, University of Gothenburg, Gothenburg, Sweden, ²Crown Princess Victoria Children's Hospital, Oslo, Sweden, ³Dept Of Biomedical And Clinical Sciences, Division of Pediatrics, Linköping, Sweden, ⁴Statistiska Konsultgruppen, Gothenburg, Sweden, ⁵Department Of Pediatric Research, Faculty of Medicine, Oslo, Norway, ⁶Children's Center, Oslo University Hospital, Oslo, Norway, ⁷Department Of Pediatrics, Queen Silvia Children's Hospital, Göteborg, Sweden

Objectives and Study: Maternal infection and antibiotic exposure during pregnancy may imprint on the developing foetal immune system and influence the offspring's susceptibility to immune‐mediated diseases. However, prospectively collected data on the risk of inflammatory bowel disease (IBD) are scarce. In a binational birth cohort study, we aimed to separately examine maternal infection and antibiotic use in pregnancy and the offspring's risk of IBD.

Methods: We followed participants from the Swedish ABIS and Norwegian MoBa cohorts from 1997‐2009 through 2020‐2021. IBD diagnosis was defined by ≥2 records in national registers. Questionnaires were used to collect data on maternal infections (any‐, gastrointestinal‐, and respiratory infections) and antibiotic treatment during pregnancy. Timing of infections was divided into early and late pregnancy. Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) for IBD and its subtypes, accounting for the child's sex, parental IBD, parental origin, maternal smoking, and maternal education level. Random‐effects meta‐analysis methods were used to pool the results across the two cohorts.

Results: We followed 117,493 children during 2,024,299 person‐years of follow‐up (IBD, n=451). Maternal infections at any time in pregnancy were not associated with offspring IBD risk (Figure 1). Any vs no infection during early pregnancy was associated with an increased risk for IBD (aHR=1.25; 95%CI=1.02‐1.53; Figure), particularly Crohn's Disease (CD) (aHR=1.41; 95%CI=1.02‐1.94), but not ulcerative colitis. While no association was found for gastrointestinal infection at any time in pregnancy, any vs no gastrointestinal infection in late pregnancy was associated with CD risk (aHR=1.96; 95%CI=1.35‐2.86). Pooled analyses showed no association between respiratory infections and offspring IBD risk. Any antibiotic during pregnancy (vs no use) was not associated with IBD in the child.

Conclusions: We observed that maternal infection during early pregnancy and gastrointestinal infection during late pregnancy was associated with the offspring's IBD risk, particularly CD.

Contact e‐mail address: annie.guo@gu.se

THE COMPLEX INTERPLAY BETWEEN EARLY‐LIFE ADVERSITIES AND RISKS OF DEVELOPING PAEDIATRIC‐ONSET IMMUNE‐MEDIATED INFLAMMATORY DISEASE

Mikkel Malham¹, Christoffer Sejling², Vibeke Wewer³, Megan Davis⁴, Samir Bhatt⁴, Matthew Fox¹, Naja Rod⁴

¹Departments Of Epidemiology And Global Health, Boston University School of Public Health, Boston, United States of America, ²Section Of Biostatistics, Copenhagen University, Copenhagen, Denmark, ³Department Of Paediatric And Adolescence Medicine, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, Denmark, ⁴Section Of Epidemiology, Copenhagen University, Copenhagen, Denmark

Objectives and Study: The aetiology of paediatric‐onset immune‐mediated inflammatory disease (pIMID) is poorly understood. Early‐life exposure studies show inconclusive results, and the interaction between exposures remains to be addressed. We aim to estimate the effect of interrelated dimensions of biological, familial, and material adversities during the first 1,000 days from conception on developing pIMID.

Methods: This nationwide study included all individuals born in Denmark from 1980 to 2018 and followed through to 2021. Early‐life adversities over the first 1,000 days from conception (exposures; Figure 1) were captured from national healthcare registers. The outcome was pIMID (defined as inflammatory bowel disease, autoimmune liver disease, juvenile idiopathic arthritis, lupus erythematosus, and vasculitis). We used Cox proportional hazards regression to estimate hazard ratios (HR) and utilised a neural network analysis called the Causes of Outcome Learning (CoOL) method to identify adversity clusters with higher risks of pIMID. Time at risk started at day 1,000 from conception.

Results: We included 2,123,827 individuals, of whom 9,356 developed pIMID. Median follow‐up was 21.9 years (Interquartile range: 14.0‐29.9). Children who experience multiple (>3) biologic (HR 1.90; 95%CI: 1.55‐2.27) or material (1.39; 95%CI: 1.15‐1.67) adversities within the first 1,000 days were at higher risk of pIMID compared to those without. Children exposed to 1‐2 familial adversities were also at moderately higher risk of developing pIMID (1.24; 95%CI: 1.11‐1.40). The CoOL method analysis identified a smaller group of children (1.2%) with a distinct combination of early‐life adversities associated with a markedly higher risk of pIMID (1.41% absolute risk compared to the baseline risk of 0.44%; Figure 1).

Conclusions: We found that early‐life adversities across multiple dimensions were associated with the risk of developing pIMID and that these adversities may cluster, making some children particularly vulnerable.

Contact e‐mail address: mikkel.malham.knudsen.01@regionh.dk

TWO DIFFERENT MECHANISMS OF NON‐SYNONYMOUS PATHOGENIC VARIANTS IN IL10RA DEFICIENCY

Juhwan Lee¹, Inki Kim², Seak Hee Oh³, Kyung Mo Kim³, Iksoo Chang⁴

¹iProtein Therapeutics, Daegu, Korea, Republic of, ²Department Of Convergence Medicine, Asan Institutes for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ³Seoul Asan Medical Center Children's Hospital, Seoul, Korea, Republic of, ⁴Supercomputing Big Data Center and Core Protein Resources Center, Daegu, Korea, Republic of

Objectives and Study: Interleukin‐10 receptor alpha (IL10RA) deficiency is one of prominent causes of refractory very early‐onset inflammatory bowel disease (VEO‐IBD). However, there is limited knowledge regarding the structural and biochemical mechanism to pathogenic effect of mutant IL10RA proteins in VEO‐IBD, since the limited human samples hinders any extensive biological research activity. In this study, we applied digital approach to comprehensively acquire the atom‐level structural and thermodynamic insight of mutant IL10RA and the subsequent experimental validation in VEO‐IBD.

Methods: We selected representative mutant IL10RA proteins exhibiting missense pathogenic variants (PVs). Our digital approach to predict distinct biochemical properties included supercomputing molecular dynamics simulations and multiplex computational assessments for PVs. Predictions were then tested through in vitro experimental validations using human cell lines and samples from patients with IL10RA‐defective VEO‐IBD.

Results: We identified two distinct pathogenic mechanisms of defective IL10RA signaling, based on mutation types in IL10RA's extracellular domain. Type I mutations (W45G, Y57C, W69R, T84I, Y91C, V100G, R101W, L125R, G141R, and I169T) were predicted to cause intra‐structure instability such as hydrophobic core collapse, hydrogen‐bond breaking, and salt‐bridge breaking. Type II mutations (R117H and R117C) were predicted to induce inter‐structure binding instability with IL‐10 without any intra‐structure instabilities. In experimental validations, Type I mutant IL10RA proteins failed to localize to the plasma membrane, and this phenomenon was explained by defective glycosylation of the mutant proteins in our subsequent analysis. Conversely, Type II mutant proteins were properly localized to the plasma membrane but failed to respond to the IL‐10 cytokine.

Conclusions: These findings provide novel insights into two different pathogenic mechanisms of IL10RA deficiency based on the types of missense mutations, which may deepen our understanding of IL10RA's role in VEO‐IBD and inform new‐drug‐development strategies based on types of mutations.

Contact e‐mail address: seakhee.oh@amc.seoul.kr

MIRIKIZUMAB PHARMAco*kINETICS AND EXPOSURE‐RESPONSE IN PEDIATRIC PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2 SHINE‐1 STUDY

Yuki Otani¹, Laiyi Chua², Wendy Komocsar³, Amy Larkin³, Xin Zhang³

¹Global Pk/pd And Pharmacometrics Department, Eli Lilly and Company, Indianapolis, United States of America, ²Eli Lilly and Company, Singapore, Singapore, ³Eli Lilly and Company, Indianapolis, United States of America

Objectives and Study: Mirikizumab is a p19‐directed anti‐interleukin‐23 antibody approved for treatment of adults with moderately to severely active ulcerative colitis (UC). Here, we report mirikizumab pharmaco*kinetics and exposure‐response in pediatric patients with moderately to severely active UC from the phase‐2, multicenter, open‐label study SHINE‐1 (NCT04004611).

Methods: Patients aged 2 to <18 years weighing >10kg with a modified Mayo score (MMS) of 4‐9 and endoscopic subscore ≥2 received intravenous mirikizumab induction doses (300mg for weight >40kg; 5 or 10mg/kg for weight ≤40kg) every 4 weeks (Q4W) through Week 12. At Week 12, patients achieving MMS clinical response received subcutaneous maintenance doses of mirikizumab 200mg (>40kg), 100mg (>20‐≤40kg), or 50mg (≤20kg) Q4W for 36 weeks. Pharmaco*kinetic parameters were analyzed by nonlinear mixed‐effects modeling with fixed allometry for size. Covariate effects on mirikizumab exposure were evaluated using simulation‐based estimations. Exposure‐response for patients achieving clinical response, remission, and endoscopic response at Weeks 12 and 52 were explored using graphical approaches.

Results: The analysis included 232 samples from 26 patients. Estimated systemic clearance, volume of distribution, and subcutaneous bioavailability were 0.000296 L/hr/kg, 0.069 L/kg, and 49.8%, respectively. Pharmaco*kinetic model‐estimated exposures in all weight groups were similar to those in adult phase‐3 studies LUCENT‐1 (NCT03518086) and LUCENT‐2 (NCT03524092) except for the 10‐mg/kg induction dose, which was 2‐fold higher (Figure). In the exposure range studied in SHINE‐1, exposure‐response analysis using post‐hoc grouping by average concentration quartile revealed no improvement trend in clinical response, remission, or endoscopic response and showed similar efficacy to that in adults.

Conclusions: Mirikizumab pharmaco*kinetic exposures and efficacy results at intended phase‐3 doses across all pediatric weight groups were similar to those reported in adults. No patient factors other than weight justify dose adjustment. Exposure‐matching to the adult exposure data and exposure‐response analysis support a phase‐3, weight group‐divided dosing strategy in pediatric patients.

Contact e‐mail address: otani_yuki@lilly.com

IMPACT ON IN UTERO EXPOSURE TO BIOLOGIC TREATMENTS FOR INFLAMMATORY BOWEL DISEASE (IBD) ON CHILDREN'S PSYChom*oTOR DEVELOPMENT: DUMBO REGISTRY OF GETECCU

Laura Palomino Pérez¹, Marta Velasco Rodríguez‐Belvís¹, Yanire Brenes Ruiz², Eduardo Leo‐Carnerero³, Cristina Calviño Suarez⁴, Montserrat Rivero⁵, Marta Calvo⁶, María Teresa Arroyo⁷, Agnes Fernández‐Clotet⁸, Isabel Pérez‐Martínez⁹, Ángeles Masedo González¹⁰, Vicent Hernández¹¹, Alexandra Ruiz‐Cerulla¹², Pilar López Serrano¹³, Pablo Vega¹⁴, Iago Rodríguez‐Lago¹⁵, Raquel Vicente Lidón¹⁶, Miguel Ángel De Jorge¹⁷, Iván Guerra¹⁸, Lara Arias García¹⁹, Gema Molina Arriero²⁰, Daniel Hervías Cruz²¹, David Busquets²², Ana Gutiérrez Casbas²³, Manuel Van Domselaar²⁴, Gemma Valldosera Gomis²⁵, Juan María Vázquez Morón²⁶, Marta Piqueras Cano²⁷, Alfredo J Lucendo²⁸, María Dolores Martín Arranz²⁹, Patricia Ramírez De La Piscina³⁰, María Del Pilar Martínez Tirado³¹, Virginia Robles Alonso³², Sandra Marín Pedrosa³³, Raquel Camargo Camero³⁴, Edisa Armesto Gonzalez³⁵, Carlos Tardillo Marín³⁶, Esther Bernardos Martín³⁷, María Carmen Rodríguez Grau³⁸, José M. Huguet³⁹, Lucía Márquez‐Mosquera⁴⁰, Pau Sendra Rumbeu⁴¹, Luis Bujanda⁴², Carlos Castaño‐Milla⁴³, Empar Sáinz Arnau⁴⁴, Luis Hernández⁴⁵, Laura Ramos⁴⁶, Mm Boscá‐Watts⁴⁷, Noemí Manceñido Marcos⁴⁸, Miquel Sans⁴⁹, Victor Jair Morales⁵⁰, Sandra Hermida Vázquez², Pablo Parra Pineda², Almudena Durán Vegue², Ana Garre², Alberto García‐Salido¹, Rosa Ana Muñoz Codoceo¹, Javier P. Gisbert², María Chaparro²

¹Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, ²Gastroenterology Unit, Hospital Universitario de La Princesa. Instituto de Investigación Sanitaria Princesa IIS‐IP‐ and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD., Madrid, Spain, ³Gastroenterology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain, ⁴Gastroenterology Unit, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain, ⁵Gastroenterology Unit, Hospital Universitario Marqués de Valdecilla e IDIVAL, Santander, Spain, ⁶Gastroenterology Unit, Hospital Universitario Puerta de Hierro, Madrid, Spain, ⁷Gastroenterology Unit, Hospital Clínico Universitario Lozano Blesa. IIS Aragón y CIBERehd, Zaragoza, Spain, ⁸Gastroenterology Unit, Hospital Clinic de Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas CIBERehd. Institut d'Investigacions Biomèdiques August Pi i Sunyer IDIBAPS, Barcelona, Spain, ⁹Gastroenterology Unit, Hospital Universitario Central de Asturias. Diet‐ Microbiota and Health Group. Instituto de Investigación Sanitaria del Principado de Asturias ISPA., Oviedo, Spain, ¹⁰Gastroenterology Unit, Hospital Universitario 12 de octubre, Madrid, Spain, ¹¹Gastroenterology Unit, Xerencia Xestión Integrada de Vigo‐ SERGAS. Grupo de Investigación de Patología Digestiva. Instituto de Investigación Sanitaria Galicia Sur IIS Galicia Sur. SERGAS UVIGO, Vigo, Spain, ¹²Gastroenterology Unit, Hospital Universitario de Bellvitge‐ L'Hospitalet de Llobregat, Barcelona, Spain, ¹³Gastroenterology Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain, ¹⁴Gastroenterology Unit, Complexo Hospitalario Universitario de Ourense, Ourense, Spain, ¹⁵Gastroenterology Unit, Hospital Universitario de Galdakao. Biobizkaia Health Research Institute, Bizkaia, Spain, ¹⁶Gastroenterology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain, ¹⁷Gastroenterology Unit, Hospital Universitario de Cabueñes, Asturias, Spain, ¹⁸Gastroenterology Unit, Hospital Universitario de Fuenlabrada, Madrid, Spain, ¹⁹Gastroenterology Unit, Hospital Universitario de Burgos, Burgos, Spain, ²⁰Gastroenterology Unit, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain, ²¹Gastroenterology Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain, ²²Gastroenterology Unit, Hospital Trueta de Girona, Girona, Spain, ²³Gastroenterology Unit, Hospital General Universitario Dr. Balmis Alicante. ISABIAL‐ CIBERehd, Alicante, Spain, ²⁴Gastroenterology Unit, Hospital Universitario de Torrejón‐ Universidad Francisco de Vitoria, Madrid, Spain, ²⁵Gastroenterology Unit, Hospital Universitario Joan XXIII, Tarragona, Spain, ²⁶Gastroenterology Unit, Hospital Universitario Juan Ramón Jimenez, Huelva, Spain, ²⁷Gastroenterology Unit, Consorci Sanitari de Terrassa CST, Barcelona, Spain, ²⁸Gastroenterology Unit, Hospital General de Tomelloso. Instituto de Investigación Sanitaria La Princesa‐ Spain‐ Instituto de Investigación Sanitaria de Castilla‐La Mancha IDISCAM‐ Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas CIBERehd, Ciudad Real, Spain, ²⁹Gastroenterology Unit, Hospital Universitario La Paz, Madrid, Spain, ³⁰Gastroenterology Unit, Hospital Universitario de Álava, Álava, Spain, ³¹Gastroenterology Unit, Hospital Clínico Universitario San Cecilio, Granada, Spain, ³²Gastroenterology Unit, Hospital Vall d'Hebrón, Barcelona, Spain, ³³Gastroenterology Unit, Hospital Universitario Reina Sofía, Córdoba, Spain, ³⁴Gastroenterology Unit, Hospital Universitario Virgen de La Victoria, Málaga, Spain, ³⁵Gastroenterology Unit, Hospital Universitario San Agustín, Avilés, Spain, ³⁶Gastroenterology Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain, ³⁷Gastroenterology Unit, Hospital Mancha Centro, Álcazar de San Juan, Spain, ³⁸Gastroenterology Unit, Hospital Universitario del Henares, Coslada, Madrid, Spain, ³⁹Gastroenterology Unit, Hospital General Universitario de Valencia, Valencia, Spain, ⁴⁰Gastroenterology Unit, 40Hospital del Mar, Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, ⁴¹Gastroenterology Unit, Hospital Universitario Son Espases, Palma de Mallorca, Spain, ⁴²Gastroenterology Unit, Bioodonostia Health Research Institute ‐ Donostia University Hospital, Universidad del País Vasco (UPV/EHU), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastián, Spain, ⁴³Gastroenterology Unit, Hospital Universitario Rey Juan Carlos,, Móstoles, Madrid, Spain, ⁴⁴Gastroenterology Unit, Hospital Sant Joan de Déu, Manresa; Hospital Universitario de La Princesa and CIBEREHD, Madrid, Spain, ⁴⁵Gastroenterology Unit, Hospital Santos Reyes Aranda de Duero SACyL, Burgos, Spain, ⁴⁶Gastroenterology Unit, Hospital Universitario de Canarias, La Laguna S/C de Tenerife, Spain, ⁴⁷Gastroenterology Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain, ⁴⁸Gastroenterology Unit, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain, ⁴⁹Gastroenterology Unit, ISADMU Centro Médico Teknon, Barcelona, Spain, ⁵⁰Gastroenterology Unit, Hospital de Granollers, Barcelona, Spain

Objectives and Study: Our aim was to evaluate the impact of the exposure of biologics in utero on the psychom*otor development of children during the first year of life.

Methods: Data from children included in the DUMBO registry with complete AQS‐3 available up to 12 months of age were analysed. DUMBO is a prospective, observational, and multicentre registry endorsed by GETECCU, which enrols pregnant women with IBD throughout 5 years in 70 centres in Spain. Study protocol is summarized in figure 1a. Normal psychom*otor development was defined by ASQ‐3 scores above the lower limit of normality (referral zone) in all domains. Serious adverse events (SAE) were defined in accordance with the ICH Topic E 2 A Clinical Safety Data Management.

Results: 352 children born to 343 mothers were included (9 pair of twins) (tables 1a, 1b and 1c). 134 children (38%) had been exposed to biologics in utero; from them, 50 (37%) had been exposed to adalimumab, 44 (32%) to infliximab, 3 (2.2%) to certolizumab, 1 (0.7%) to golimumab, 28 (20%) to ustekinumab, and 10 (7.5%) to vedolizumab. 8% of the mothers were smokers during pregnancy; no other toxic consumption (alcohol or drugs) was recorded. The ASQ‐3 results across different domains are presented in figure 1b, and the impact of the different factors associated with the neurodevelopment is summarised in table 1d. In the multivariate analysis, to have been born to a mother with CD (vs. UC) was associated with higher likelihood (OR=2, 95%CI=1.1‐3.9), while to be premature was associated with lower likelihood (OR=0.3, 95%CI=0.1‐0.6) of having ASQ‐3 scores above the limit of normality in all domains at 12 months of age.

Conclusions: In the multicenter, prospective DUMBO registry, the exposure to biologics for the treatment of IBD in utero (including anti‐TNF and non‐anti‐TNF agents) did not impair the psychom*otor development of the children.

Contact e‐mail address: laura_palomino_perez@hotmail.es

THE EFFECT OF MILK‐DERIVED EXTRACELLULAR VESICLES (MDES) ON INTESTINAL EPITHELIAL CELLS OF IBD PATIENTS

Shimon Reif¹, Myriam Grunewald^2,3, Liron Birimberg‐Schwartz^2,4, Mirit Musseri¹, Regina Golan Gerstl¹

¹Pediatrics, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel., Jerusalem, Israel, ²Hadassah Organoid Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ³Department Of Developmental Biology And Cancer Research, Faculty Of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, ⁴Pediatric Gastroenterology, Hadassah Hebrew University Medical Center, JERUSALEM, Israel

Objectives and Study: The pathogenesis of Inflammatory Bowel Diseases (IBD) is considered to be multifactorial, comprising factors such as immune dysregulation, environmental influences, microbial dysbiosis, and genetic predispositions of the host. Milk‐derived exosomes (MDEs) are nanovesicles that transport microRNA (miRNA). We demonstrated that MDEs are internalized by IECs and impart a therapeutic and anti‐inflammatory effect in a murine model of colitis. This study aimed to determine the impact of MDEs on human IECs.

Methods: We have employed organoids derived from human intestinal biopsies from IBD patients and healthy controls. Gene and miRNA expression were analyzed by qRT‐PCR. Proliferation was analyzed by immunofluorescent staining of Ki67.

Results: We demonstrated that MDEs were internalized by the organoids. The expression of miRNAs that are abundant in MDEs, such as miR‐148, was significantly higher in organoids treated with MDEs compared to untreated ones (10.44 ± 0.17 vs. 4.06 ± 0.76). DNMT1, a target gene of miR‐148, was significantly downregulated in MDE‐treated organoids (from 0.49 8± 0.037 to 0.064 ± 0.011). Additionally, other MDE‐associated miRNAs showed significantly increased levels in treated organoids: Let‐7a (2.05 ± 0.06 vs. 1.37 ± 0.025) and miR‐30 (7.85 ± 0.51 vs. 5.44 ± 0.9). The expression of HSP70 was significantly upregulated in organoids following MDE treatment (from 0.45 ± 0.026 to 0.95 ± 0.053). Incubation with MDEs in the culture medium of intestinal organoids induced enhanced epithelial cell proliferation, as evidenced by significantly increased Ki67 staining. Moreover, the expression of β‐catenin, at the protein level, which is involved in intestinal epithelium integrity and barrier function, was upregulated in organoids treated with MDEs in comparison to untreated controls.

Conclusions: Our findings demonstrate that MDEs promote proliferation and modulate gene expression in human intestinal organoids, highlighting their potential as a preclinical tool for investigating MDE impacts on human IECs and intestinal homeostasis, with implications for their clinical use.

Contact e‐mail address:

CROHN'S DISEASE EXCLUSION DIET AS ADD‐ON THERAPY IN REFRACTORY PEDIATRIC PATIENTS

Luca Scarallo¹, Elena Banci², Monica Paci³, Sara Naldini³, Sara Renzo³, Jacopo Barp³, Alessia De Blasi³, Paolo Lionetti¹

¹Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS and Department of NEUROFARBA, University of Florence, Florence, Italy, ²Dietetics Unit, Meyer Children Hospital IRCCS, Florence, Italy, Florence, Italy, ³Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS, Florence, Italy, Florence, Italy

Objectives and Study: We aimed at assessing efficacy of Crohn's disease exclusion diet (CDED) + partial enteral nutrition (PEN) in re‐inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies.

Methods: This was a single‐center, retrospective study conducted at a national referral pediatric IBD center. Incident patients who received CDED + PEN in the setting of the loss of response (LoR) to other maintenance therapies were included.

Results: 25 patients [52% males, median disease duration: 31 months (Q1‐Q3: 8.4‐13.8)]. were included. The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti‐TNF‐alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Figure 1). Weighted Pediatric Crohn's Disease Activity Index (wPCDAI), c‐reactive protein (CRP) and fecal calprotectin (FC) significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p<0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission (wPCDAI < 12.5), 15 (60%) had CRP levels within normal range (<0.5 mg/dL) and 7 (28%) had normalized FC (<150 mg/kg). 18 (72%) patients had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of < 12.5 after a complete course of EEN) were more likely to achieve clinical remission when treated with CDED + PEN (11/13 vs 1/5, p=0.022).

Conclusions: CDED + PEN is a valid treatment strategy in the setting of secondary LOR to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “dietary responder” patients.

Contact e‐mail address:

LAG‐3+ CD4+ T CELLS REPRESENT A PREDICTIVE BIOMARKER FOR INFLIXIMAB THERAPY RESPONSE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Alexander Schnell¹, Carmen Aicher², Philipp Schnegelsberg², Benedikt Schwarz², Hannah Schmidt², Ida Allabauer¹, Aline Rueckel¹, Adrian Regensburger¹, Joachim Woelfle², André ho*rning¹

¹Pediatric Gastroenterology And Hepatology, Department Of Pediatrics And Adolescent Medicine, University Hospital Erlangen, Friedrich‐Alexander‐University Erlangen‐Nuremberg, Erlangen, Germany, ²Department Of Pediatrics And Adolescent Medicine, University Hospital Erlangen, Friedrich‐Alexander‐University Erlangen‐Nuremberg, Erlangen, Erlangen, Germany

Objectives and Study: T cells are thought to be one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is able to induce remission by neutralizing TNFα, a central cytokine of the inflammatory cascade. In this study, we determined the individual cytokine profile in pediatric IBD patients before and during 12 months of IFX therapy in order to identify predictive biomarkers for therapy success.

Methods: Blood samples were collected before initiation of IFX and after three, six and twelve months under therapy. CD4⁺ cells were immunomagnetically isolated, in vitro stimulated with CD3/CD28 beads and IL‐2 for 72h and subsequently evaluated for cytokine production by intracellular flow cytometry. Response status to IFX therapy was defined as a fecal calprotectin level below 100µg/g or achieving levels <10% of the baseline value at the end of follow up period.

Results: A total of n=42 pediatric IBD patients (CD, n=30; UC, n=12) prior to Infliximab therapy were recruited. 14 healthy age‐matched children served as control subjects (HC). 21 patients were classified as responders (RS) and 21 patients as non‐responders (NRS). Before initiation of IFX therapy, the cytokine profile of T cells was highly skewed towards pro‐inflammatory cytokines such as TNF‐α, IFN‐γ and IL‐21 in all IBD patients. However, T cells of NRS displayed an increased TNF‐a/IL‐10 ratio and higher fractions of Granzyme B‐producing T cells. Moreover, NRS also displayed higher frequencies of in vitro stimulated Lag‐3⁺ T cells which proved to significant predictive marker for therapy failure (AUC = 0.86, p = 0.0007).

Conclusions: T cells of pediatric IBD patients display an activated and rather Th1‐shifted phenotype. Moreover, the increased expression of the checkpoint molecule Lag‐3 (under in vitro stimulation) on T cells of non‐responding patients may indicate a more exhausted phenotype than in responding patients and healthy controls which appeared to be a relevant predictive marker for therapy failure

Contact e‐mail address: alexander.schnell@uk‐erlangen.de

ENDOSCOPIC HEALING IN PAEDIATRIC IBD PERPETUATES A PERSISTENT SIGNATURE CHARACTERIZED BY PATHOGENIC TH17 CELLS AND TISSUE‐ASSOCIATED MOLECULAR AND MICROBIAL DRIVERS OF DISEASE

Kolja Siebert¹, Nikolai Köhler², Tim Faro¹, Monica Matchado³, Hannes Hoelz¹, Sebastian Jarosch⁴, Federica De Zen¹, Deborah Haecker⁵, Mohammad‐Samer Hajji¹, Eberhard Lurz¹, Sibylle Koletzko¹, Klaus Neuhaus⁶, Caspar Ohnmacht⁷, Markus List³, Dirk Busch⁴, Dirk Haller⁵, Tobias Schwerd¹

¹Department For Paediatric Gastroenterology, Hepatology & Nutrition, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany, ²Chair Of Experimental Bioinformatics ‐ Lipitum, Technical University of Munich (TUM), Freising, Germany, ³Chair Of Experimental Bioinformatics ‐ Data Science In Systems Biology, Technical University of Munich (TUM), Freising, Germany, ⁴Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), TUM School of Medicine, Munich, Germany, ⁵Chair Of Nutrition And Immunology, Technical University of Munich (TUM), Freising, Germany, ⁶Ziel‐institute For Food & Health, Technical University of Munich (TUM), Freising, Germany, ⁷Center Of Allergy And Environment Zaum‐ Research Center For Environmental Health, Technical University of Munich and Helmholtz Center Munich, Neuherberg, Germany

Objectives and Study: Endoscopic healing (EH) is the major treatment target for inflammatory bowel diseases (IBD) but may not prevent disease exacerbation. We aimed to identify tissue‐associated molecular and microbial drivers of IBD under EH.

Methods: We performed transcriptomic analyses of whole biopsies and isolated CD45⁺CD3⁺ single T‐cells (10X Genomics) from longitudinally collected endoscopic samples (terminal ileum [TI] and sigmoid colon [SC]) of children with IBD and compared these results to non‐IBD controls. Mucosa‐associated microbiota was analyzed by 16S‐rRNA gene sequencing.

Results: 217 biopsies (n=135 simultaneous extraction of host‐RNA and bacterial‐DNA; n=82 single T‐cell analysis) from 32 pediatric IBD patients (mean age 13±3.5 years, 21 Crohn's disease, 11 ulcerative colitis, 15 newly‐diagnosed) and 5 non‐IBD controls were analyzed. Time between baseline (T1) and endoscopic follow‐up (T2) was 40 ± 22 weeks (T1: N=32, T2: N=32; T>2: N=6). At baseline, 31/32 patients had active inflammation and 22/31 achieved EH (SES‐CD≤2 and absence of ulcerations) at T2, mostly on anti‐TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. Bulk RNA sequencing analysis facilitated the identification of 299 differentially expressed genes (DEGs; corrected p‐value <0.05, FC >2.0), such as DUOX2, SAA2‐SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non‐IBD controls. In addition, single cell analysis of 72,026 CD45⁺CD3⁺ T‐cells revealed an IBD‐specific pathogenic Th17 cluster that persisted in EH and showed high correlation with top DEGs after data integration. 16S‐rRNA gene sequencing highlighted highly individual mucosa‐associated bacterial profiles and a reduced α‐diversity in active and EH compared to non‐IBD controls.

Conclusions: A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity despite EH and mucosal regeneration in comparison to non‐IBD controls. These markers may provide targets for future or sequential therapies.

Contact e‐mail address: tobias.schwerd@med.uni‐muenchen.de

THE NANCY HISTOPATHOLOGICAL INDEX HAS LIMITED VALUE IN PREDICTING CLINICAL OUTCOMES IN NEWLY DIAGNOSED PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS

Yaniv Faingelernt^1,2, Irit Birger³, Sara Morgenstern^4,5, Eyal Cohen‐Sela⁵, Manar Matar^1,5, Yael Weintraub^1,5, Raanan Shamir^1,5, Dror Shouval^1,5

¹Institute Of Gastroenterology, Nutrition And Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel, ²Faculty Of Health Sciences, Ben‐Gurion University of the Negev, Beer Sheva, Israel, ³Department Of Pediatrics B, Schneider Children's Medical Center, Petach Tikva, Israel, ⁴Institute Of Pathology, Rabin Medical Center, Petach Tikva, Israel, ⁵Faculty Of Medicine, Tel Aviv University, Tel Aviv, Israel

Objectives and Study: The Nancy Histological Index (NHI) is a relatively new tool to score histological features in patients with ulcerative colitis (UC). it is still unclear whether markers of disease severity, at diagnosis, have an impact on long term disease outcomes in pediatric UC. Our goal was to assess the utility of NHI at diagnosis in predicting clinical outcomes in pediatric UC patients, in comparison to clinical and endoscopic scores.

Methods: Methods: A retrospective analysis of newly diagnosed pediatric UC patients between 2016‐2023. We collected data regarding Pediatric UC Activity Index (PUCAI), Mayo Endoscopic Score (MES) and NHI upon diagnosis. Survival analysis was performed to determine association with treatment escalation to azathioprine and anti‐TNFa therapy, along with acute severe colitis (ASC) episodes during follow‐up.

Results: Data was collected on 106 patients, 59 (55.7%) were females; median age at diagnosis was 14.4 (IQR 11.2–15.9) years. Median PUCAI score at diagnosis was 35 (IQR 25‐55) and 15 (16.1%) patients presented with ASC. Most patients had moderate‐severe disease, based on endoscopic and histological features. Most patients received for induction oral 5‐aminosalicylic acid or sulfasalazine therapy (81.3%), steroids were used in 37.7% and salvage anti‐TNFa therapy during 1^st induction occurred in 4.7%. During follow‐up, 33 patients (31.1%) required azathioprine therapy, and 32 (30.2%) were escalated to anti‐TNFa drugs. Evaluating different indices at diagnosis, PUCAI and MES were significantly associated with escalation to anti‐TNFa therapy (P=0.036 and P=0.02, respectively), but not initiation of azathioprine or subsequent ASC events. However, the NHI was not associated with subsequent azathioprine or anti‐TNFa therapy (P=0.42 and P=0.78, respectively), nor with future ASC episodes (P=0.70).

Conclusions: The NHI failed to predict clinical outcomes in newly‐diagnosed pediatric patients with UC. Prospective studies are required to define whether the NHI or other histological scores can assist in risk stratification of pediatric UC patients.

Contact e‐mail address: ianivf@gmail.com

TOBACCO SMOKE EXPOSURE IN EARLY CHILDHOOD AND LATER RISK OF INFLAMMATORY BOWEL DISEASE: A SCANDINAVIAN POPULATION‐BASED BIRTH COHORT STUDY

Ida Sigvardsson¹, Johnny Ludvigsson^2,3, Björn Andersson⁴, Ketil Stordal^5,6, Karl Mårild^1,7

¹Department Of Pediatrics, Institution of clinical sciences, Göteborg, Sweden, ²Dept Of Biomedical And Clinical Sciences, Division of Pediatrics, Linköping, Sweden, ³Crown Princess Victoria Children's Hospital, Region Östergötland, Linköping, Sweden, ⁴Bioinformatics And Data Centre, Sahlgrenska Academy, Göteborg, Sweden, ⁵Department Of Pediatric Research, Faculty of Medicine, Oslo, Norway, ⁶Children's Center, Oslo University Hospital, Oslo, Norway, ⁷Department Of Pediatrics, Queen Silvia Children's Hospital, Göteborg, Sweden

Objectives and Study: To examine the association between early‐life smoking exposure and later risk of inflammatory bowel disease (IBD).

Methods: We followed 115,663 participants from the population‐based Norwegian Mother, Father and Child (MoBa) and All Babies in Southeast Sweden (ABIS) cohorts from birth (1997‐2009) through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke (ETS) exposure during pregnancy, and child ETS exposure by age 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios (aHRs) for sex, maternal age, education level, parental IBD and origin. Cohort‐specific estimates were pooled using a random‐effects model.

Results: During 1,987,430 person‐years of follow‐up, 444 participants developed IBD (ABIS, n=112; MoBa, n=332). Any vs. no maternal smoking during pregnancy yielded a pooled aHR of 1.30 (95%CI=0.97–1.74) for offspring IBD. Higher level of maternal smoking during pregnancy (compared to no smoking, average ≥6 cigarettes/day: pooled aHR=1.60 [95%CI 1.08–2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1–5 cigarettes/day: pooled aHR=1.09 [95%CI=0.73–1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs. no ETS, pooled aHR=1.32 [95%CI=1.03–1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant.

Figure 1. Pooled analyses of early‐life smoking exposure and later risk of inflammatory bowel disease in the ABIS and MoBa birth cohorts. Adjusted hazard ratio (aHR) for sex, parental IBD, parental origin, maternal age, and maternal education level. CI, confidence interval; ETS, environmental tobacco smoke; HR, hazard ratio.

Conclusions: In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD, independent of potential confounders.

Contact e‐mail address: ida.sigvardsson@gu.se

DOSE TO TROUGH: HIGHER DOSE INFLIXIMAB INDUCTION ACHIEVES BETTER MAINTENANCE TROUGH LEVELS IN A NATIONAL PAEDIATRIC IBD COHORT

Emily Stenke^1,2, Dahlal Alhassan¹, Molly Moclair¹, Sarah Cooper^1,2, Anna Dominik^1,2, Rita Mackey¹, Karen O'Driscoll¹, Ciara Lang¹, Shoana Quinn^1,2, Annemarie Broderick^1,2,3,4, Emer Fitzpatrick^1,3, Billy Bourke¹, Seamus Hussey^1,2

¹National Centre For Paediatric Gastroenterology, Hepatology And Nutrition, Children's Health Ireland at Crumlin, Dublin, Ireland, ²Dochas Study, Children's Health Ireland at Crumlin, Dublin, Ireland, ³School Of Medicine, University College Dublin, Dublin, Ireland, ⁴National Children's Research Centre, Dublin, Ireland

Objectives and Study: Proactive drug monitoring of recommended target infliximab (IFX) trough levels (TLs) of ≥15 ug/ml pre‐3^rd dose and ≥5ug/ml pre subsequent doses shows that standard 5mg/kg dosing is often inadequate. In addition, many phenotypes require higher target TLs. Our national service commenced empiric 10mg/kg standard dosing after 2018.

Methods: This was a retrospective study of Irish patients commenced on 5mg or 10mg/kg IFX between 2018 and 2020. Dosing regimens and responses to proactive TL monitoring were at physician discretion. The primary outcome was adequate pre‐4^th TL (≥5ug/ml). Data source verification and analysis was undertaken retrospectively. Clinical, laboratory and pharmacy data, including durability of IFX to 1 year were recorded.

Results: IFX was commenced in 116 patients (73% male; 73% CD, 25% UC, 2% IBDU; mean age at diagnosis 11.8 ± SD 2.7 years; 53 commenced 5mg/kg; mean time to IFX after diagnosis was 12 (± SD 19) months). Baseline parameters were comparable between groups. Patients in the 5mg/kg group were more likely to have suboptimal pre‐4^th TLs (34/40 (85%) vs 21/48 (44%), p< 0.001; mean (±SD) TLs 3.6 (±6.9) vs 9.7 (±9.9), p=0.001). The 5mg/kg group were more likely to have suboptimal pre‐3^rd TLs (94% vs 25%, p<0.001); more likely to have treatment escalation (79% vs 49%, p= 0.001), less likely to de‐escalate (12% vs 32%, p=0.01), but had lower cumulative IFX exposure (76 vs 97 mg/kg/year, p<0.001). Binomial regression analysis including baseline CRP, ESR, albumin, age at diagnosis and disease duration identified IFX levels ≥15 at pre‐3^rd dose as predictive of therapeutic TLs (≥5) pre‐4^th (OR 6.9, 95% CI 2.3‐20.6).

Conclusions: Our real‐world data show that inadequate pre‐3^rd TLs strongly predict suboptimal pre‐4^th levels. Without proactive monitoring, standard 5mg/kg dosing may lead to early suboptimal maintenance TLs and compromise sustaining IFX durability in paediatric IBD, especially among patients with higher therapeutic trough requirements.

Contact e‐mail address: emily.stenke@childrenshealthireland.ie

EFFICACY AND SAFETY OF MIRIKIZUMAB THERAPY IN PEDIATRIC PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS: FINAL RESULTS FROM THE PHASE 2 SHINE‐1 STUDY

Jess Kaplan¹, Athos Bousvaros², Dan Turner³, Marla Dubinsky⁴, Wendy Komocsar⁵, Amy Larkin⁵, Jordan Johns⁵, Xin Zhang⁵, Wallace Crandall⁵, Vipin Arora⁵, Kris Todd⁵, Jeffrey Hyams⁶

¹Mass General for Children, Boston, United States of America, ²Boston Children's Hospital, Boston, United States of America, ³Juliet Keidan Institute Of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ⁴The Mount Sinai Hospital, New York, United States of America, ⁵Eli Lilly and Company, Indianapolis, United States of America, ⁶Connecticut Children's Medical Center, Hartford, United States of America

Objectives and Study: Mirikizumab is a humanized immunoglobulin G4 monoclonal antibody against the p19 subunit of interleukin‐23, a key inflammatory mediator in ulcerative colitis (UC). Here we report efficacy and safety in pediatric patients with moderate to severe UC from the Phase 2 SHINE‐1 study (NCT04004611) following 52 weeks of mirikizumab treatment.

Methods: Patients aged 2 to <18 years with active UC who had an inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies, or had corticosteroid‐dependent colitis, were included in the study. Patients weighing >40 kg received an induction dose of 300 mg via intravenous infusion; patients weighing ≤40 kg received 5 or 10 mg/kg via intravenous infusion at weeks 0, 4, and 8. At week 12, patients were assessed for clinical response using the Modified Mayo Score. Responders entered the maintenance period and received subcutaneous doses of mirikizumab at 200 mg (>40 kg), 100 mg (>20 kg to ≤40 kg), or 50 mg (≤20 kg) once every 4 weeks, with the last patient visit at week 52.

Results: All patients (N=26) completed induction through week 12, and 73.1% (N=19) completed through week 52. At week 12, 69.2% (18/26) were Modified Mayo Score responders; at week 52, 55.6% (10/18) of responders were in clinical and endoscopic remission. Clinical response, remission, and endoscopic remission rates were consistent with LUCENT Phase 3 UC adult studies (Figure 1). The safety profile of mirikizumab was consistent with the safety profile in LUCENT adults. Three serious adverse events (11.5%) were reported: non‐infective appendicitis, UC flare, and pseudarthrosis. The UC flare resulted in study discontinuation.

Conclusions: Mirikizumab demonstrated an acceptable safety profile, and similar clinical response, clinical remission, and endoscopic remission compared to LUCENT adults. These results are the foundation of the pivotal Phase 3 pediatric SHINE‐2 study.

Contact e‐mail address: larkin_amy_e@lilly.com

PREDICTING RESPONSE TO NUTRITIONAL THERAPY IN NEWLY DIAGNOSED CHILDREN WITH CROHN'S DISEASE (CD) USING MULTI‐OMICS APPROACH

Asaf Azulay^1,2, Yonat Aharoni Frutkoff^1,2, Yshewayeh Shimhlash^1,2, Elhanan Borenstein^3,4,5, Leah Reshef⁶, Luba Plotkin^1,2, Gili Focht^1,2, Tasia Maslov^1,2, Esther Orlanski‐Meyer^1,2, Raffi Lev‐Tzion^1,2, Oren Ledder^1,2, Dotan Yogev^1,2, Amit Assa^1,2, Dan Turner^1,2

¹Juliet Keidan Institute Of Pediatric Gastroenterology Hepatology And Nutrition, Shaare Zedek Medical Center; Hebrew University of Jerusalem, Jerusalem, Israel, ²Faculty Of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ³Faculty of Medicine‐ Tel Aviv University, Tel Aviv, Israel, ⁴School of Computer Science‐ Tel Aviv University, Tel Aviv, Israel, ⁵Santa Fe Institute, Santa Fe, United States of America, ⁶The Shmunis School of Biomedicine and Cancer Research‐ George S. Wise Faculty of Life Sciences‐ Tel Aviv University, Tel Aviv, Israel

Objectives and Study: One‐third of children with Crohn's disease(CD) will fail treatment with exclusive enteral nutrition(EEN) but predictors of response have been hitherto lacking. In this prospective‐cohort study, we aimed to use multiomic data to predict EEN response in treatment‐naïve children with CD.

Methods: Children commenced on EEN at CD onset were followed through 8 weeks. Stool was collected for microbiome and metabolomics, and serum for metabolomics. Disease indices and clinical‐data were recorded. Targeted‐quantitative‐metabolomics approach was applied to analyze fecal and serum samples using a combination of direct injection mass‐spectrometry with a reverse‐phase LC‐MS/MS custom‐assay. DNA extracted from stool was sequenced and 16S‐rRNA gene was amplified. Feature selection was utilized, using Recursive Feature Elimination with Cross‐Validation. For each omic analysis and multiomic integration, selected components were fitted into machine learning random forest models.

Results: 51 children(14.8±2.7yrs) treated with EEN were included, of whom 34(66%) were responders; 36(70%) had serum‐metabolomics, 20(39%) fecal‐metabolomics and 31(61%) microbiome‐data, 17(33%) had all components. Clinical‐data did not predict response(Figure.A). The individual omic models ranked key metabolites and microbes(Figure.B‐E) and were able to predict EEN response with an accuracy ranging at 0.806‐0.850 (Figure.A). Serum‐3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropionic‐acid(CMPF), fecal‐phenylethylamine and fecal‐alpha‐aminobutyric‐acid were higher in non‐responders while serum‐malic‐acid and fecal‐3‐methyladipic‐acid were higher in responders(Figure.B‐C). Levels of species Veillonela, Bifidobacterium and Blautia genus were higher in responders while Lachnospiraceae and Fusicatenibacter genus were higher in non‐responders(Figure.D). The multiomic model, with clinical‐data included, retained components from serum and fecal metabolomics but none from the microbiome; it predicted EEN response with high accuracy of 0.882(Figure.A). Higher levels of serum‐2‐hydroxyglutraic‐acid, 2‐hydroxy‐2‐methylbutyric‐acid and fecal‐3‐methyladipic‐acid were detected in responders. In non‐responders there were higher levels of serum‐alpha‐aminobutyric‐acid, valeric‐acid, isovaleric‐acid, alpha‐aminobutyric‐acid and kynrenine and alongside with increased fecal‐kynrenine/tryptophan ratio, both part of tryptophan‐metabolism and kynrenine‐tryptophan pathway(Figure.E).

Conclusions: In this multiomic analysis, we generated metabolomics‐based multiomic model to predict response to EEN, unravelling related biological insights.

Contact e‐mail address: asafazu@szmc.org.il

MAINTENANCE VEDOLIZUMAB TREATMENT IN PEDIATRIC IBD: LONG TERM RESULTS OF THE PROSPECTIVE MULTICENTER VEDOKIDS STUDY

Ohad Atia¹, Zivia Shavit‐Brunschwig¹, Gili Focht¹, Raffi Lev‐Tzion¹, Ronen Stein², Efrat Broide³, Darja Urlep^4,5, Jeffrey Hyams⁶, Batia Weiss⁷, Marina Aloi⁸, Amit Assa¹, Richard Russell⁹, Dan Turner¹

¹Juliet Keidan Institute Of Pediatric Gastroenterology, Hepatology And Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel, ²Division Of Gastroenterology, Hepatology And Nutritiona, Children's Hospital of Philadelphia, Philadelphia, United States of America, ³Shamir Medical Center, Beer Yaakov, Israel, ⁴Children's Hospital of the University Medical Center Ljubljana, Ljubljana, Slovenia, ⁵Pediatric Gastroenterology And Liver Unit, Children's Hospital‐ University Medical Centre Ljubljana‐ Ljubljana‐ Slovenia., Department of Gastroenterology‐ Hepatology and Nutrition, Ljubljana, Slovenia, ⁶Clinic Of Pediatrics, Connecticut Children's Medical Center, Hartford, United States of America, ⁷Pediatric Gastroenterology And Nutrition, Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel, ⁸Department Of Women's And Children's Health, Pediatric Gastroenterology And Liver Unit, Sapienza University of Rome, Rome, Italy, ⁹Division Of Pediatric Gastroenterology, The Royal Hospital for Children & Young People, Edinburgh, United Kingdom

Objectives and Study: Prospective long‐term data on vedolizumab in pediatric Crohn's disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort VEDOKIDS study, we aimed to evaluate the effectiveness and safety of maintenance therapy with vedolizumab in pediatric CD and UC.

Methods: Children commenced on vedolizumab were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and fecal calprotectin were repeatedly obtained. The primary outcome was sustained steroid‐free remission (SSFR), defined as clinical‐remission)PUCAI<10/wPCDAI<12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle.

Results: SSFR rates of 137 enrolled children (73 [53%] UC, 64 [47%] CD) were 40% in UC and 23% in CD (OR 2.2 [95%CI 1.03‐4.7]; Figure). SSFR rate was higher in week‐6 responders versus non‐responders in UC (50% vs 22%, OR 2.9 [1.1‐7.7]) and CD (35% vs 13%, OR 3.3 [95%CI 0.96‐11.6]). Of those with mild disease at week‐6, 31% of CD and 48% of UC achieved SSFR, while none of children with moderate‐severe CD (0/14) and 7% (1/15) of moderate‐severe UC achieved SSFR. The best predictors for SSFR was wPCDAI at week‐6 for CD (optimal cutoff 17.5 points; AUROC 0.89 [95%CI 0.81‐0.97]), and PUCAI at week‐14 for UC (0.73 [0.62‐0.84]; with optimal cutoff of 5 points). In children <30kg, SSFR was achieved in 57% of those having vedolizumab levels ≥30ug/mL at week‐6 compared with 27% with >30ug/mL. By week 54, 197 adverse events were recorded, of which eight were vedolizumab‐related (5.8%), and 2 (1.4%) led to discontinuing vedolizumab. There was 1 lymphoma case judged to be unrelated to VDZ vedolizumab.

Conclusions: Vedolizumab was effective for maintaining remission in children, more so in UC. The likelihood of eventually achieving SSFR was very low in children with moderate‐severe disease or those not responding to induction therapy.

Contact e‐mail address: turnerd@szmc.org.il

FOUR RNA EXPRESSION GENES CAN GUIDE ANTI‐TNF TREATMENT IN CHILDREN WITH CROHN'S DISEASE: A PORTO GROUP STUDY

Ohad Atia¹, Asaf Azulay², Gili Focht³, Yshewayeh Shimhlash³, Lorenzo Norsa⁴, Marina Aloi⁵, Michal Kubát⁶, Jiří Bronský⁶, Michael Bergel², Botros Moalem², Danny Ben Zvi², Dan Turner³

¹Juliet Keidan Institute Of Pediatric Gastroenterology, Hepatology And Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel, ²Faculty Of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, ³Juliet Keidan Institute Of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ⁴Pediatric Hepatology, Gastroenterology and Transplantation Department, ASST Papa Giovanni XXIII, Bergamo, Italy, ⁵Pediatric Gastroenterology And Liver Unit, Department Of Women's And Children's Health, Sapienza University of Rome, Rome, Italy, ⁶Department Of Paediatrics, University Hospital Motol, Prague, Czech Republic

Objectives and Study: Studies exploring genes that their expression may predict response to biologics in Crohn's disease (CD), were hitherto all in adults and had inconsistent results. In this Porto‐group study, we aimed to explore the predictive utility of genes expressed in intestinal biopsies of children with CD prior to initiation of biologic.

Methods: We prospectively enrolled children with CD prior to initiating anti‐tumor necrosis factor (TNF) in four centers participating in the Porto‐group biobank. Clinical data were recorded at treatment initiation and 4 and 12 months thereafter. We included biopsies from inflamed terminal‐ileum and compared, in an extreme group proof of concept analysis, those who achieved steroid‐ and EEN‐free remission (wPCDAI<12.5; SFR) at 12 months with those experiencing primary non‐response (PNR). Feature selection was applied using Recursive Feature Elimination with Cross‐Validation. Selected genes were fitted into a machine learning regression model which was evaluated using repeated cross validation and permutation test. Genes were pre‐selected to the analysis from systematic review of the literature showing some association with therapeutic response.

Results:

We included 19 children (12 SFR and 7 PNR; age 13.1±2.6 years; median disease duration 3.6 months [IQR 0.1‐6.1]). Twenty‐four genes associated with response to anti‐TNF were first identified, of which 13 were retained after filtering the low expressed genes. Following feature selection, higher expression of four genes were associated with SFR: PTGS2, CXCL6, G0S2 and HCAR3. A multivariable model of these four achieved high predictive utility with AUROC of 0.90 (95%CI 0.87‐0.94; sensitivity/specificity 93%/80% and PPV/NPV 89% and 88%, respectively (Figure).

Conclusions: Increased mucosal PTGS2, CXCL6, G0S2 and HCAR3 expression ia associated with higher likelihood of 1‐year SFR in children with CD initiating anti‐TNF. Real‐life cohort study is now warranted to validated these genes as potential biomarkers for therapy selection.

Contact e‐mail address: turnerd@szmc.org.il

OUTCOME OF COLORECTAL CANCER SURVEILLANCE IN PAEDIATRIC INFLAMMATORY BOWEL DISEASE: TIME FOR NEW GUIDELINES?

Eva Vermeer^1,2,3, Cornélus Palsma¹, Ramon Gorter⁴, Robert De Jonge⁵, Joris Roelofs⁶, Nanne De Boer^2,7, Tim De Meij^1,2,3

¹Paediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands, ²Amsterdam Gastroenteroloy, Endocrinology And Metabolism (agem) Research Institute, Amsterdam UMC, Amsterdam, Netherlands, ³Amsterdam Reproduction And Development (ar&d) Research Institute, Amsterdam UMC, Amsterdam, Netherlands, ⁴Paediatric Surgery, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands, ⁵Laboratory Medicine, Amsterdam UMC, Amsterdam, Netherlands, ⁶Pathology, Amsterdam UMC, Amsterdam, Netherlands, ⁷Gastroenterology & Hepatology, Amsterdam UMC, Amsterdam, Netherlands

Objectives and Study: Paediatric inflammatory bowel disease (IBD) patients have an increased risk of colorectal cancer (CRC). Current guidelines advise to conduct CRC surveillance colonoscopy eight years following IBD diagnosis, or more often in case other risk factors for CRC are present, such as previous findings of colorectal dysplasia, or a concomitant primary sclerosing cholangitis (PSC) diagnosis. However, these guidelines are based on adult data and with no regard to the patient's age. In this study, we aimed to estimate the risk of dysplasia and CRC in paediatric IBD patients before the ages of 18 and 27 years.

Methods: Using the Dutch Nationwide Pathology Databank (PALGA), we examined the incidence and prevalence of dysplasia and CRC in patients up to 27 years in all Dutch paediatric IBD patients diagnosed between 1991 and 2023. Additionally, we assessed the influence of PSC on CRC risk.

Results: Out of the 7,873 patients with biopsy‐proven paediatric IBD, 24 developed dysplasia (0.34%) and two (0.025%) developed CRC before the age of 18 years. Out of the 3,425 patients from this cohort currently aged over 26 years, eleven (0.3%) developed CRC between 17 and 27 years. Overall, 120 patients (1.5%) were diagnosed with PSC, seven (5.8%) of which developed dysplasia and two (1.6%) of which developed CRC before the age of 27 years. The median time between IBD and CRC diagnosis was 9.5 years in this cohort.

Conclusions: In this retrospective study, we found low prevalence of dysplasia and CRC in paediatric IBD patients, both before the age of 18 years and before the age of 27 years. We showed that PSC significantly increased the risk of CRC in paediatric IBD patients. Based on our findings it could be proposed to initiate CRC surveillance beyond the age of 18 years by experienced adult gastroenterologists, except in case of a concomitant PSC diagnosis.

Contact e‐mail address: e.vermeer@amsterdamumc.nl

EFFICACY AND SAFETY OF ADALIMUMAB IN VERY EARLY‐ONSET IBD‐ A MULTICENTRE STUDY FROM THE PAEDIATRIC IBD PORTO GROUP OF ESPGHAN

Yael Weintraub¹, Lauran Collen Veit², Seamus Hussey³, Katarina Mitrova⁴, Nicholas Croft⁵, Ben Kang⁶, Maya Granot⁷, Giulia D'Arcangelo⁸, Elizabeth Spencer⁹, Kaija‐Leena Kolho¹⁰, Pai Jui Yeh¹¹, Malgorzata Sladek¹², Luca Scarallo¹³, Laura Palomino Pérez¹⁴, Nadeem Afzal¹⁵, Jan De Laffolie¹⁶, Erasmo Miele¹⁷, Matteo Bramuzzo¹⁸, Ola Olén^19,20, Richard Russell²¹, Pejman Rohani²², Christos Tzivinikos²³, Darja Urlep²⁴, Patrick Van Rheenen²⁵, Lissy De Ridder²⁶, Dotan Yogev²⁷, Anna‐Maria Schneider²⁸, Shlomi Cohen²⁹, Ruth Garci Romero³⁰, Valeria Dipasquale³¹, Holm Uhlig³², Dror Shouval¹

¹Institute Of Gastroenterology, Nutrition And Liver Diseases, Schneider Children's Medical Center and the Faculty of Medicine, Tel Aviv University, Petach Tikva, Israel, ²Division Of Gastroenterology, Hepatology, And Nutrition, Department Of Pediatrics,, Boston Children's Hospital and Harvard Medical School, Boston, United States of America, ³Children's Health Ireland, UCD and RCSI, Dublin, Ireland, ⁴Department Of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol,, Prague, Czech Republic, ⁵Faculty Of Medicine, Blizard Institute, Queen Mary University Of London, and Paediatric Gastroenterology, Royal London Children's Hospital, Barts Health NHS Trust, London, United Kingdom, ⁶Department Of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea, Republic of, ⁷Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ⁸Pediatric Gastroenterology And Liver Unit, Umberto I Hospital, Sapienza University of Rome, Rome, Italy, ⁹Division of Pediatric Gastroenterology & Nutrition, Department of Pediatrics, Icahn School of Medicine, Mount Sinai, New York, United States of America, ¹⁰Department Of Pediatric Gastroenteroloy, Children's Hospital, University of Helsinki and HUS, Helsinki, Finland, ¹¹Translational Gastroenterology Unit, University of Oxford, Oxford, United Kingdom, ¹²Polish‐American Children's Hospital, Jagiellonian University, Cracow, Poland, ¹³Gastroenterology and Nutrition Unit, Meyer Children Hospital IRCCS and Department of NEUROFARBA, University of Florence, Florence, Italy, ¹⁴Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, ¹⁵Department of Paediatric Gastroenterology, Southampton Children's Hospital and, University of Portsmouth, Southampton, United Kingdom, ¹⁶General Pediatrics & Pediatric Gastroenterology, Justus‐Liebig‐University, Gießen, Germany, ¹⁷Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ¹⁸Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy, ¹⁹Division Of Clinical Epidemiology, Department Of Medicine Sona, Karolinska Institutet, Stockholm, Sweden, ²⁰Pediatric Gastroenterology And Nutrition Unit, Sachs' Children's Hospital, Stockholm, Sweden, ²¹Department of Paediatric Gastroenterology, Royal Hospital for Children and Young People, Edinburgh, United Kingdom, ²²Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran, ²³Paediatric Gastroenterology Department, Al Jalila Children's Specialty Hospital, Mohammed Bin Rashid University, Dubai Medical College, Dubai, United Arab Emirates, ²⁴Children's Hospital‐ University Medical Centre Ljubljana‐ Ljubljana‐ Slovenia., Department of Gastroenterology‐ Hepatology and Nutrition, Ljubljana, Slovenia, ²⁵University of Groningen. University Medical Center Groningen. Department of Paediatric Gastroenterology, Groningen, Netherlands, ²⁶Paediatric Gastroenterology, Erasmus MC‐ Sophia children's hospital, Rotterdam, Netherlands, ²⁷Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center and The Hebrew University of Jerusalem, Jerusalem, Israel, ²⁸Department Of Pediatrics, Paracelsus Medical University, Salzburg, Austria, ²⁹Pediatric Gastroenterology Institute, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ³⁰Pediatric Gastroenterology And Nutrition Unit, Miguel Servet Hospital, Zaragoza, Spain, ³¹Pediatric Gastroenterology And Cystic Fibrosis Unit, Department Of Human Pathology In Adulthood And Childhood "g. Barresi", University Hospital "G. Martino", Messina, Italy, ³²Translational Gastroenterology Unit and Department of Paediatrics and Biomedical Research Centre, University of Oxford, Oxford, United Kingdom

Objectives and Study: Patients with very early onset inflammatory bowel disease (VEOIBD) often present with severe disease course and require escalation to biologics. Efficacy and safety data on TNFa antagonists therapy in this patient population are lacking. We aimed to assess safety and efficacy of Adalimumab induction and maintenance therapy in patients with VEOIBD.

Methods: A retrospective study involving 31 sites affiliated with the IBD Porto Group and IBD Interest Group of ESPGHAN, as well as centers in North America. Demographic, clinical and laboratory data were collected from patients diagnosed with VEOIBD who commenced Adalimumab therapy before the age of 6 years.

Results: We identified 77 VEOIBD patients with a median age at diagnosis of 2.6 (interquartile range [IQR] 1.3–4.1) years. Thirty‐seven (48%) patients were diagnosed with Crohn's disease (CD), 25(32%) with ulcerative colitis (UC) and 15(20%) with IBD‐unclassified. Forty‐four patients (57%) were Infliximab experienced, discontinued mainly due to pharmaco*kinetic (45%) and pharmacodynamic (30%) failures. Median age at initiation of Adalimumab was 4.2(IQR 2.8‐5.1) years, concomitant corticosteroids and immunomodulators were given in 37(48%) and 29(37%) patients, respectively. Median follow‐up time was 85.4(IQR 40.4‐139.2) weeks. Significant clinical improvement was observed in patients with CD after 26 and 52 weeks but not in patients with UC (Figure 1). Inflammatory markers showed gradual decrease over time. ADM discontinuation rates after 1 and 3 years were 40% and 65%, respectively, mainly due to primary non‐response (30%) and loss of response (40%). Drug discontinuation rates were not dependent on age or concomitant immunomodulator treatment at time of Adalimumab initiation. Four patients (5%) developed severe infections, including one patient with TTC7A mutation who died following septic shock.

Conclusions: Adalimumab therapy was relatively safe and seemed more effective in CD, but not in UC. Durability however was relatively low.

Contact e‐mail address:

EFFECTIVENESS AND SAFETY OF USTEKINUMAB IN PEDIATRIC ULCERATIVE COLITIS: A MULTI‐CENTER STUDY FROM THE PEDIATRIC IBD PORTO GROUP OF ESPGHAN

Anat Yerushalmy‐Feler¹, Helena Jonsson Rolandsdotter², Kaija‐Leena Kolho³, Dan Turner⁴, Christos Tzivinikos⁵, Matteo Bramuzzo⁶, Gemma Pujol‐Muncunill⁷, Luca Scarallo⁸, Darja Urlep⁹, Firas Rinawi¹⁰, Maya Granot¹¹, Ben Kang¹², Ylva Longueville¹³, Marta Velasco Rodríguez‐Belvís¹⁴, Yael Weintraub¹⁵, Victor Navas‐López¹⁶, Shlomi Cohen¹

¹Pediatric Gastroenterology Institute, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ²Department of Clinical Science and Education, Karolinska Institute, and Department of Gastroenterology, Sachs' Children and Youth Hospital, Stockholm, Sweden, ³Department Of Pediatric Gastroenteroloy, Children's Hospital, University of Helsinki and HUS, Helsinki, Finland, ⁴Juliet Keidan Institute Of Pediatric Gastroenterology Hepatology And Nutrition, Shaare Zedek Medical Center; Hebrew University of Jerusalem, Jerusalem, Israel, ⁵Paediatric Gastroenterology Department, Al Jalila Children's Specialty Hospital, Mohammed Bin Rashid University, Dubai Medical College, Dubai, United Arab Emirates, ⁶Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy, ⁷Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu,, Barcelona, Spain, ⁸Gastroenterology and Nutrition Unit, Meyer Children's Hospital, 50139, Florence, Italy, ⁹Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, 1000, Ljubljana, Slovenia, ¹⁰Pediatric Gastroenterology Unit, Emek Medical Centre, Afula, Israel, Faculty of Medicine, Technion, Afula, Israel, ¹¹Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ¹²Department Of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea, Republic of, ¹³Pediatric Gastroenterology Unit, Karolinska University Hospital, Stockholm, Sweden, ¹⁴Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, ¹⁵Institute Of Gastroenterology, Nutrition And Liver Diseases, Schneider Children's Medical Center and the Faculty of Medicine, Tel Aviv University, Petach Tikva, Israel, ¹⁶Pediatric Gastroenterology And Nutrition, HOSPITAL REGIONAL UNIVERSITARIO DE MALAGA, MALAGA, Spain

Objectives and Study: Current data on ustekinumab (UST) therapy in children with ulcerative colitis (UC) and unclassified inflammatory bowel disease (IBDU) are limited. This multicenter study aimed to evaluate the effectiveness and safety of UST in pediatric UC and IBDU.

Methods: A retrospective study from 16 centers affiliated with the IBD interest and Porto groups of ESPGHAN. Children with UC and IBDU who were treated with UST were included. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded.

Results: Fifty‐eight children [39 UC, 19 IBDU, median (interquartile range) age 14.5 (11.5‐16.5) years] were included. They had all failed previous biologic therapies and 38 (66%) failed at least 2 biologic agents. Corticosteroids‐free clinical remission (CFR) was observed in 25 (45%), 31 (55%) and 35 (63%) at 16, 26 and 52 weeks, respectively. Normalization of C‐reactive protein and decrease in fecal calprotectin to <150 mcg/g at 52 weeks were achieved in 60% and 52%, respectively. Endoscopic and radiologic remission were reached in 14% and 12%, respectively, among the 58 children in the intention‐to‐treat group. The main predictors to CFR were diagnosis of UC compared to IBDU (HR=2.242, 95%CI 1.034‐4.854, P=0.041) and absence of prior vedolizumab therapy (HR=2.179, 95%CI 1.111‐4.273, P=0.023). While UST serum level < 1 mcg/ml was associated with active disease, serum levels were comparable between children in clinical remission and children with active disease. Adverse events were reported in 6 (10%) children, leading to discontinuation of therapy in 3 children. The adverse events included: death due to an acute episode of severe diarrhea, interstitial nephritis, hypersensitivity reaction, breast abscess, injection site reaction and cytomegalovirus infection.

Conclusions: UST therapy is effective in children with refractory UC and IBDU. The potential efficacy should be weighed against the risk of serious adverse events.

Contact e‐mail address: anaty11@yahoo.com

PREVALENCE OF HELICOBACTER PYLORI INFECTION AMONG SLOVENIAN CHILDREN: A PROSPECTIVE COHORT STUDY

Matjaž Homan¹, Anja Šterbenc², Uroš Godnov³, Polona Maver Vodičar², Saša Simčič², Samo Jeverica², Živa Zaletel⁴, Pia Homan⁴, Eva Miler Mojškerc⁵

¹Department Of Gastroenterology, Hepatology, And Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, ²Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, ³Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, Slovenia, ⁴Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, ⁵Department of Pediatrics, Slovenj Gradec General Hospital, Slovenj Gradec, Slovenia

Objectives and Study:Helicobacter pylori infection is primarily acquired in childhood and is notably influenced by socioeconomic variances across different geographical regions. The aim of this study is to assess the prevalence of H. pylori infection in Slovenian children and to identify potential risk factors that facilitate the infection.

Methods: Between 2019 and 2022, we conducted a multi‐center prospective cross‐sectional study among healthy children residing in three different statistical regions in Slovenia. H. pylori infection status was determined using a monoclonal antibody‐based stool antigen test (SAT). A standardized questionnaire was designed to evaluate the influence of various H. pylori‐associated risk factors.

Results: During the 3‐year period, we recruited 426 children (age range 2‐19 years, mean age 10.37 ± 5.01 years). Overall, 46 (10.8%) were diagnosed with an H. pylori infection. As shown in Figure 1, no associations were found between H. pyloriprevalence rates and increasing age, gender, parental education level, country of origin of the child or their parents, number of household members, household income, having a dishwasher, having a pet, duration of breastfeeding, fruit intake frequency, drinking tap water or handwashing practices. The only parameters associated with an increased risk of infection was the location of the school (p < 0.001) and living in an urban area (p = 0.035). The odds of infection were approximately 4.87 times higher if the child attended school in the central compared to other regions (OR = 4.87, 95% CI [0.89, 2.36]).

Conclusions: This is the first study providing information on the prevalence of H. pylori infection among Slovenian children. Using SAT, we have shown that the burden of H. pylori infection in our pediatric population is low; however, it seems to depend on regional rather than socioeconomic factors.

Contact e‐mail address:

HELICOBACTER PYLORI INFECTION FOUND DURING UPPER ENDOSCOPY PERFORMED FOR THE DIAGNOSIS OF THE MOST COMMON PEDIATRIC GASTROINTESTINAL DISEASES. A MULTICENTER PEDIATRIC EUROPEAN STUDY

Kallirroi Kotilea¹, Claudio Romano², Erasmo Miele³, Angelika Kindermann⁴, Yael Dolstra⁵, Zrinjka Mišak⁶, Vaidotas Urbonas⁷, Joseph Sykora⁸, Pedro Urruzuno⁹, Alexander Krauthammer¹⁰, Maria Rogalidou¹¹, Konstantina Dimakou¹², Tsili Zangen¹³, Eleftheria Roma¹⁴, Aglaia Zellos¹⁴, Maria Luz Cilleruelo¹⁵, Meline M'Rini¹, Patrick Bontems¹, Yasin Sahin¹⁶, Marta Tavares¹⁷, Tatevik Shahinyan¹⁸, Biljana Vuletic¹⁹, Nicolas Kalach²⁰, Michal Kori^21,22

¹Pediatric Gastroenterology, Université Libre de Bruxelles‐Hôpital Universitaire de Bruxelles‐Hôpital Universitaire Des Enfants Reine Fabiola, Brussels, Belgium, ²Paediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology, University of Messina, Messina, Italy, ³Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ⁴Department Of Pediatric Gastroenterology, Hepatology, And Nutrition,, Emma Children's Hospital, Amsterdam UMC, Amsterdam, Netherlands, ⁵Paediatric Division, Kaplan Medical Centre, Rehovot, Israel, ⁶Referral Centre for Paediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia, ⁷Clinic of Children's Diseases of Vilnius University Faculty of Medicine, Vilnius,, Lithuania, ⁸Charles University in Prague, Faculty of Medicine in Pilsen, Prague, Czech Republic, ⁹Department of Pediatric Gastroenterology, Hospital Universitario Doce de Octubre, Madrid, Spain, ¹⁰Pediatric Gastroenterology Unit, Edmond and Lily Safra Children's Hospital Sheba Medical Center, Tel‐Hashomer, Israel, Ramat Gan, Israel, ¹¹Division Of Gastroenterology And Hepatology, First Department Of Pediatrics, University Of Athens, Children's Hospital Agia Sofia, Athens, Greece, ¹²Gastroenterology department, Agia Sofia Children's Hospital, Athens, Greece, ¹³Pediatric Gastroenterology And Nutrition Unit, Wolfson medical center, Holon, Israel, ¹⁴Division of Paediatric Gastroenterology and Hepatology, Mitera Children's Hospital, Athens, Greece, ¹⁵Pediatric Gastroenterology Unit. Puerta de Hierro Majadahonda Hospital, Madrid, Spain, ¹⁶Division of Pediatric Gastroenterology, Gaziantep Islam Science and Technology University Medical Faculty, Gaziantep, Turkey, ¹⁷Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte, Centro Hospitalar e Universitário de Santo António, Porto, Portugal, ¹⁸Arabkir Institute of Child and Adolescent Health, Yerevan, Armenia, ¹⁹University of Kragujevac, Faculty of Medical Sciences Department of Pediatrics, Kragujevac, Serbia, ²⁰Saint Antoine Paediatric Clinic, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University, Lille, France, ²¹Pediatric Gastroentrology, Kaplan Medical Center, Rehovot, Israel, ²²Faculty Of Medicine, Hebrew University of Jerusalem, jerusalem, Israel

Objectives and Study:Helicobacter pylori (H. pylori) gastritis may be an incidental finding during upper gastrointestinal endoscopy (UGE) performed to diagnose Celiac disease (CeD), Inflammatory bowel disease (IBD) and Eosinophilic Esophagitis (EoE). We aimed to describe the incidence of H. pylori in children undergoing UGE for CeD, IBD, and EoE in Europe and determine the indications for treatment.

Methods: A retrospective, multicenter study including 19 centers from 14 countries, reviewing endoscopy reports of pediatric patients diagnosed with CeD, IBD, and EoE between 1/2019 and 12/2021. Data collected: age, gender, hematologic parameters, endoscopic, histologic and H. pylori culture results, and information on eradication treatment.

Results:H. pylori was diagnosed in 349/3890 (9%) children, [167 (48%) male, median age 12 (interquartile range 8.1‐14.6) years] during UGE performed for the diagnosis of CeD, IBD and EoE. H. pylori was present in 173/1733 (10%) CeD, 110/1292 (8.5%) IBD and 66/865 (7.6%) EoE patients (p=ns). The incidence of H. pylori differed significantly between regions (Eastern Europe 5.2% (28/536), Southern Europe 3.8 % (78/2032), Western Europe 5.5% (28/513)) and 26.7% (216/810) in the Middle East (OR 7.96 95%CI (6.31‐10.1) p<0.0001). Eradication treatment was recommended in 131/349 (37.5%) patients, 34.6% of CeD, 35.8% of IBD, and 56.1% of EoE patients. Predictors identified for recommending treatment included: the presence of erosions/ulcers (OR 6.45 95% CI 3.62‐11.47, p<0.0001) and gastric nodularity (OR 2.25 95% CI 1.33‐3.81, p=0.003). Patients living in countries with a low H. pylori incidence (<20%) were more likely to be treated (OR 3.36 95%CI 1.47‐7.66 p=0.004).

Conclusions: Identifying H. pylori infection incidentally during UGE in children varies significantly among European regions but not among the common GI diseases. The indications for recommending treatment in this setting are not well defined, with less than 40% of children receiving treatment.

Contact e‐mail address: kalliroy.kotilea@hubruxelles.be

ERADICATION RATE OF HELICOBACTER PYLORI INFECTION IN VIETNAMESE CHILDREN: A PROSPECTIVE SINGLE TERTIARY CENTER STUDY

Camtu Nguyen^1,2, Phuong Nguyen³, Dinh Truong⁴, Hiep Nguyen⁵, Annie Robert⁶, Patrick Bontems⁷

¹Faculty Of Medicine, Universite Libre de Bruxelles, Brussels, Belgium, ²Department Of Gastroenterology, City Children's Hospital, Ho Chi Minh City, Viet Nam, ³Department Of Biostatistics And Informatics, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam, ⁴Pediatric Surgery, City Children's Hospital, Ho Chi Minh City, Viet Nam, ⁵Faculty Of Public Health, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam, ⁶Pôle Epidémiologie Et Biostatistique (epid), Institut De Recherche Expérimentale Et Clinique (irec), Faculté De Santé Publique (fsp), Université Catholique de Louvain, Brussels, Belgium, ⁷Pediatric Gastroenterology, Université Libre de Bruxelles‐Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium

Objectives and Study: This study aimed to assess the treatment outcomes in Vietnamese children using current eradication regimens, considering susceptibility testing results (AST).

Methods: Consecutive H. pylori‐diagnosed pediatric patients were recruited at City Children's Hospital in HoChiMinh City. The eradication regimen was prescribed following ESPGHAN guidelines, considering the AST results if available. The outcome was evaluated through a monoclonal immunoassay stool test (Premier®PlatinumHpSA®PLUS) six weeks after treatment.

Results: A total of 109 H. pylori‐positive patients (mean age: 10.1 ± 2.8 years; 52% boys) received eradication treatment for peptic ulcers (23/109, 21%), erosion (23%), nodularity (47%), and erythema (9%). Among them, 53 (49%) had available AST results, revealing resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), amoxicillin (AMO), and tetracycline (TET) resistance rate at 74%, 42%, 55%, 21%, and 0%, respectively. Heteroresistance was observed only for MET in two patients. The most common first‐line regimen was esomeprazole, AMO, MET (60/109; 55%), followed by esomeprazole, AMO, MET, bismuth subcitrate (33%), esomeprazole, AMO, CLA (4.6%), and other regimens (LEV or TET‐based)(7.4%). After treatment, 70 patients returned for follow‐up and provided stool test results. The overall eradication rate was 59% (41/70) in per‐protocol analysis and 38% (41/109) in intention‐to‐treat analysis. The AST‐guided regimens had a higher eradication rate than empiric therapy, but the difference was not significant (Table1).

Conclusions: High antibiotic resistance rates and low eradication rates highlight the need for appropriate antibiotic intervention and management strategies in Vietnamese children.

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JUVENILE POLYPOSIS IN CHILDREN: EXPLORING THE IMPACT OF SMAD4 AND BMPR1A MUTATIONS ON CLINICAL PHENOTYPE AND POLYP BURDEN

Shlomi Cohen¹, Anat Yerushalmy‐Feler¹, Isabel Rojas², Claudia Phen², David Rudnick³, Colleen Flahive⁴, Steven Erdman⁴, Ramit Magen‐Rimon⁵, Ivana Čopová⁶, Thomas Attard⁷, Andrew Latchford⁸, Warren Hyer⁸

¹Pediatric Gastroenterology Institute, Dana‐Dwek Children's Hospital, Tel Aviv, Israel, ²Pediatric Gastroenterology, Children's Health, Dallas, United States of America, ³Washington University School of Medicine St. Louis, St. Louis, United States of America, ⁴Nationwide Children's Hospital, Columbus, United States of America, ⁵Pediatric Gastroenterology Unit, Rambam Medical Center, Haifa, Israel, ⁶University Hospital Motol, Prague, Czech Republic, ⁷Children's Mercy Hospital, Kansas City, United States of America, ⁸St Mark's Hospital, London, United Kingdom

Objectives and Study: A germline disease‐causing variant (DCV) in the SMAD4 or BMPR1A genes is identified in 40‐60% of patients with juvenile polyposis syndrome (JPS). Current guidelines for surveillance do not differentiate between children with JPS based on mutation status. The aim of this study was to characterize the clinical course and polyp burden in children with DCV‐positive JPS compared to DCV‐negative JPS.

Methods: Anonymized data of children with JPS were compiled from eight centers via an international pediatric polyposis registry granted by ESPGHAN. Demographic, clinical, genetic and endoscopic data were collected.

Results: A total of 124 children with JPS were included: 69 (56%) DCV‐negative and 55 (44%) DCV‐positive [53% SMAD4, 47% BMPR1A], with a median follow‐up of 4 (IQR 2.8‐6.4) years. DCV‐positive children were diagnosed at an older age [median (IQR) of 12 (8‐15.7) vs 5 (4‐7) years, p<0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs 1.4%, p<0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs 5.8%, p<0.001), and underwent more gastrointestinal surgeries (16.4% vs 1.4%, p=0.002) compared to DCV‐negative children. The incidence rate ratio (IRR) for development of new colonic polyps during the follow‐up was 6.149 (95% CI 3.927‐9.628, p<0.001) in the DCV‐positive group compared to the DCV‐negative group, with an average of 12.2 versus 2 new polyps for every year of follow‐up, respectively. No difference in the polyps burden was observed between patients with SMAD4 and BMPR1A mutations.

Conclusions: In this largest international cohort of pediatric JPS, DCV‐positive and negative children exhibit distinct clinical phenotype. A significantly higher burden of polyps was detected in DCV‐positive children, suggesting a potential need for differentiated surveillance strategies based on mutation status.

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ANTHOCYANINS INHIBIT THE ENZYMATIC MODIFICATION OF GLIADIN BY TRANSGLUTAMINASE 2 IN VITRO

Andrea Diers^1,2, Anika Wagner¹, Silvia Rudloff^1,2, Sebastian Stricker²

¹Department Of Nutritional Science, Justus Liebig University Giessen, Giessen, Germany, ²Department Of Pediatrics, Justus‐Liebig‐University Giessen, Giessen, Germany

Objectives and Study: Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) plays a crucial role in the pathogenesis of celiac disease (CD) and is considered a possible target for therapeutic interventions. Anthocyanins (ACN) are bioactive plant constituents which mainly occur in red‐violet to bluish fruit varieties. It has been shown that ACNs have the ability to form complexes with gliadins. Here, we investigated the effect of the main ACN representatives cyanidin and delphinidin on the interaction of digested gliadin with TG2.

Methods: TG2‐mediated crosslinking of a pepsin/trypsin‐digested gliadin (PTG) in the presence of ACNs was quantified by photometry at 655 nm (substrate: tetramethylbenzidine). Cyanidin and delphinidin were used at concentrations of 50 and 100 µM. The selective irreversible TG2 inhibitor ERW1041 served as a control. The amount of crosslinked PTG was determined by using a gliadin specific antibody and quantified by photometry. Transamidation of PTG by TG2 in the presence of ACNs at 100‐fold molar excess was further investigated by immunoblotting using a gliadin specific antibody.

Results: Both ACNs reduced the TG2‐mediated crosslinking of PTG in a concentration dependent manner with a significant reduction at a concentration of 100 µM. Cyanidin decreased the TG2 activity by 40 % (p < 0.05) and appeared to be less effective than delphinidin, which reduced the TG2 activity by 64 % (p < 0.01). Immunoblotting experiments confirmed a reduced TG2‐mediated crosslinking in the presence of delphinidin. The decrease was less pronounced compared to the effects observed with the TG2‐inhibitor ERW1041.

Conclusions: Our research findings indicate that ACNs, especially delphinidin, inhibit the enzymatic modification of digested gliadin by TG2 suggesting a therapeutic potential for ACNs in the pathogenesis of CD.

Contact e‐mail address: Andrea.Diers‐1@ernaehrung.uni‐giessen.de

NON‐BIOPSY DIAGNOSIS OF PAEDIATRIC COELIAC DISEASE WITHOUT ANTI‐ENDOMYSIAL IGA ANTIBODY TESTING: COMBINING ANTI‐TISSUE TRANSGLUTAMINASE IGA AND ANTI‐DEAMIDATED GLIADIN IGG ANTIBODIES

Marsus Pumar¹, Sharon Choo¹, Jeremy Rosenbaum², George Alex², Shaun Ho²

¹Department Of Allergy And Immunology, The Royal Children's Hospital Melbourne, Parkville, Australia, ²Department Of Gastroenterology And Clinical Nutrition, The Royal Children's Hospital Melbourne, Parkville, Australia

Objectives and Study: To determine the utility of anti‐tissue transglutaminase IgA antibodies (tTG‐IgA) and anti‐deaminated gliadin peptide IgG antibodies (DGP‐IgG) in detecting coeliac disease (CD) and whether DGP‐IgG can replace anti‐endomysial IgA antibody in the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) non‐biopsy CD diagnostic pathway.

Methods: Children aged <19 years who had tTG‐IgA and DGP‐IgG performed and had a gastroscopy with biopsies between 1 March 2016 and 31 October 2020 were identified.

Results: Of 1206 patients who fulfilled the study criteria, 303 (25.1%) patients were diagnosed with CD. Fifteen patients with IgA deficiency were excluded from any tTG‐IgA analysis. tTG‐IgA had sensitivity and specificity of 93.5 and 92.0%, respectively in detecting CD, while DGP‐IgG had sensitivity of 97.0% and specificity of 86.7%. tTG‐IgA ≥10x upper limit of normal (ULN) alone had a specificity of 99.3% and a positive predictive value (PPV) of 96.8%. An optimal DGP‐IgG threshold was identified to be 70 U/mL (3.5x ULN) based on >99% specificity in detecting CD. When tTG‐IgA ≥10x ULN was combined with DGP‐IgG ≥3.5x ULN, the PPV in diagnosing CD was 98.5%. DGP‐IgG performed well in detecting CD in 126 children aged <3 years, with all patients with CD having an elevated DGP‐IgG (sensitivity 100%).

Conclusions: Both tTG‐IgA and DGP‐IgG had high sensitivity and specificity in detecting CD in children. The combination of tTG‐IgA ≥10x ULN and DGP‐IgG ≥3.5x ULN can be considered as an alternative non‐biopsy approach to diagnose CD in selective children.

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HUMAN UMBILICAL CORD ENDOTHELIAL CELL MATRIX AS A NOVEL SENSITIVE SUBSTRATE FOR ENDOMYSIAL ANTIBODY DETECTION IN CLINICAL PRACTICE

Ilma Korponay‐Szabo^1,2, Robert Kiraly³, Judit Gyimesi², Markku Mäki⁴

¹Paediatrics, University Of Debrecen, Debrecen, Hungary, ²Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary, ³Biochemistry And Molecular Biology, University Of Debrecen, Debrecen, Hungary, ⁴Celiac Disease Research Center, Faculty Of Medicine And Health Technology, Tampere University, Tampere, Finland

Objectives and Study: Serum anti‐transglutaminase antibody IgA values (TGA) above ten times of the upper limit of normal (≥10xULN), verified by endomysial antibody (EMA) positivity from a second sample, are accepted as the basis for the non‐biopsy diagnosis of coeliac disease (CeD). EMA detections on the classical substrates, monkey oesophagus or human umbilical cord are less sensitive than TGA and both the preparation of the tissue slides and the reading are time‐consuming and need expertise. Moreover, it is getting difficult to get commercial slides for the testing. Human umbilical cord vein‐derived endothelial cells (HUVECs) produce in cell culture a regular extracellular matrix (ECM) resembling endomysial network with similar exposure of celiac‐relevant transglutaminase epitopes as in tissue sections. The aim of this study was to evaluate the diagnostic performance of EMA testing on HUVEC‐ECM.

Methods: Ninety new paediatric patients consecutively referred to our center between May–September 2023 in reason of positive coeliac antibody results in outside laboratories or by various rapid tests were prospectively tested for EMA‐IgA on HUVEC‐ECM prepared on 18‐well plastic slides. Results were compared with those of our hospital's TGA‐IgA ELISA and EMA‐IgA performed in 1:2.5 dilutions on a composite substrate containing monkey oesophagus, human umbilical cord and gut wall tissues.

Results: TGA‐IgA, EMA‐IgA on tissues and EMA‐IgA on HUVEC‐ECM were positive in 73, 62 and 67 samples with 94.4%, 92.9% and 95.7% accuracies for the final CeD diagnosis (non‐invasive + biopsy‐based), respectively. In 17 samples all three antibodies were negative; most of these patients had only TGA‐IgG or DGP earlier.

Conclusions: This user‐friendly EMA test based on easily available HUVEC‐ECM substrate provided high sensitivity and specifcity and also may improve the evaluation of coeliac autoimmunity when TGA is low positive or borderline.

Contact e‐mail address: ilma.korponay‐szabo@tuni.fi

COELIAC DISEASE AT TYPE 1 DIABETES ONSET IN CHILDREN: THE IMPACT OF THE SARS‐COV‐2 PANDEMIC

Federica Malerba^1,2, Noemi Zampatti¹, Angela Calvi³, Anna Bratta¹, Bianca De Grande¹, Nicola Minuto⁴, Marta Bassi^1,4, Giacomo Tantari⁴, Giuseppe D'Annunzio⁴, Paolo Gandullia², Stefania Proietti^5,6, Stefano Bonassi^5,6, Marco Crocco^1,2

¹Department Of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Child And Maternal Health (dinogmi), University of Genoa, Genova, Italy, ²Paediatric Gastroenterology And Endoscopy Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy, ³Independent Researcher, Genova, Italy, ⁴Paediatric And Endocrinology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy, ⁵Clinical And Molecular Epidemiology, IRCCS San Raffaele Roma, Roma, Italy, ⁶Department Of Human Sciences And Quality Of Life Promotion, San Raffaele University, Roma, Italy

Objectives and Study: The incidence of Type 1 Diabetes (T1DM) in children has increased during recent years, however, little is known about the prevalence of Coeliac Disease (CD) in newly T1DM diagnosed. Our retrospective single‐centre study aimed to investigate the influence of the Sars‐Cov‐2 pandemic on disease co‐occurrence.

Methods: We collected data on CD autoimmunity at T1DM onset in children diagnosed between January 2016 and November 2023. Paediatric patients (<18 years) with available anti‐transglutaminase IgA (TGA‐IgA) at T1DM onset were included, while those already diagnosed with CD or with IgA deficiency were excluded. Chi‐Square test and autocorrelation factor were used for comparisons.

Results: We enrolled 201 (91% of 221 eligible) children, mean age 9.2±4.2 years. The prevalence of positive TGA‐IgA at T1DM onset was 14.4% (29/201). Overall, 52% (15/29) had high TGA‐IgA titers (>10x the upper limit of normal), whereas 38% showed low‐fluctuating TGA‐IgA titers with spontaneous normalization. During the Sars‐Cov‐2 pandemic, we observed, within an increasing trend of T1DM incidence, a marked peak in the co‐occurrence of positive CD autoimmunity (Fig.1A) at T1DM onset and, also, of confirmed CD diagnoses (Fig.1B). The prevalence of positive CD autoimmunity and confirmed CD diagnoses appears to be reverting to pre‐ Sars‐Cov‐2 values in the limited post‐pandemic observation period, as confirmed by the approximation to zero of the autocorrelation factor at the end of the observation period, revealing the likely end of the perturbation.

Conclusions: Our findings showed an upward trend in CD autoimmunity and overt CD during the Sars‐Cov‐2 pandemic in newly T1DM diagnosed, suggesting the need for further investigation of its potential pathogenetic role in disease co‐occurrence. Further and multi‐prospective studies are needed to validate this hypothesis.

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SHORT ORAL GLUTEN CHALLENGE IN PATIENTS WITH CELIAC DISEASE: A PRECLINICAL VALIDATION

Stefania Picascia¹, Ilaria Mottola¹, Roberta Mandile², Renata Auricchio^3,4, Luigi Greco⁴, Riccardo Troncone², Carmen Gianfrani¹

¹Biomedicine, Institute of Biochemistry and Cell Biology ‐ CNR, Naples, Italy, ²Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ³Department Of Translational Medical Science, Section Of Pediatrics, University of Naples "Federico II", Naples, Italy, ⁴European Laboratory for the Investigation of Food‐Induced Diseases (ELFID), University Federico II, Naples, Italy, Naples, Italy

Objectives and Study: Objectives and Study: Celiac disease (CD) is T cell‐mediated autoimmune disorder triggered by gluten proteins. In the last twenty years, the short (3‐days) gluten challenge (SGC) has been proposed as sensitive bioassay to monitor the recruitment in the blood of intestinal gluten‐reactive T‐cells in CD patients. Here, we review our experience in order to highlight the applicability of this tool in CD studies.

Methods: Methods: Forty CD patients (N=8 aged 9‐12 years; N=25 aged 13‐18 years; N=7 >18 years) on a gluten free diet for at least two years were enrolled in the context of different projects to undergo a brief (3‐days) wheat gluten consumption; they ate 150‐200 g/day of bread slices, corresponding to 12‐20 g/day of gluten. The immune reactivity to whole deamidated gliadin and to the immunodominant α‐gliadin peptide (QLQPFPQPQLPYPQPQP) was analysed at day 6 by IFN‐γ‐ELISPOT assay on peripheral blood mononuclear cells (PBMCs).

Results: Results: We found that SGC mobilize a significant number of IFN‐γ‐secreting cells in response to deamidated gliadin (mean value of IFN‐γ SFC/10⁶ PBMCs was 34 at day 0, and 116 at day 6, p<0.05) and to α‐gliadin peptide (mean value of IFN‐γ SFC/106 PBMCs was 22 at day 0 and 86 at day 6, p<0.05). When we stratified IFN‐γ responses by age, we found in younger patients (9‐12 years) a greater number of IFN‐γ‐secreting cells at baseline, nevertheless, they showed a significantly increased immunoreactivity to gliadin at day 6 (p<0.05) and variable IFN‐γ‐responses to α‐gliadin peptide (p=ns), compared to those found in the older CD (aged 13‐18 years and >18 years).

Conclusions: Conclusions: We have successfully set‐up the brief gluten challenge procedure in CD patients at different age and confirmed that gluten‐reactive T cells are activated in vivo in CD upon gluten ingestion. Here, we highlight the great translational potentiality of this bioassay for clinical studies.

Contact e‐mail address: stefania.picascia@ibbc.cnr.it

DOES ROTAVIRUS INFECTION PLAY A ROLE IN THE LOSS OF TOLERANCE TO GLUTEN?

Enriqueta Roman¹, Carlos Ochoa², Ricardo Torres‐Peral³, Cristóbal Coronel Rodríguez⁴, Maria Luz Cilleruelo⁵, Josefa Barrio⁶, Ester Donat⁷, Luis Ortigosa⁸, Eva Martinez Ojinaga⁹, Raquel Vecino¹⁰, Gemma Castillejo¹¹, David Pérez Solís¹²

¹Pediatric Gastroenterology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, ²Pediatric Gastroenterology, Hospital Vigen de la Concha, Zamora, Spain, ³Complejo Asistencial Universitario Salamanca, Salamanca, Spain, ⁴Pediatrics, Centro de Salud Amante Laffon, Sevilla, Spain, ⁵Pediatric Gastroenterology Unit. Puerta de Hierro Majadahonda Hospital, Madrid, Spain, ⁶Paediatrics, Hospital Universitario de Fuenlabrada, Madrid, Spain, ⁷Pediatric Gastroenterology And Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain, ⁸Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de la candelaria, Santa Cruz de Tenerife, Spain, ⁹Pediatric Gastroenterology, Hospital Universitario La Paz, Madrid, Spain, ¹⁰Pediatric Gastroenterology, Hospital Clínico San Carlos, Madrid, Spain, ¹¹Pediatric Gastroenterology, Hospital Universitario San Juan de Reus, Reus, Spain, ¹²Pediatric Gastroenterology, Hospital San Agustín, Avilés, Spain

Objectives and Study: Rotavirus infection stands as the leading cause of acute gastroenteritis among children under five years old. This infection has been evaluated as a potential risk factor for autoimmune diseases like celiac disease. Consequently, the association between rotavirus vaccination and the risk of celiac disease has been explored in various studies, yielding controversial results. Objective: To assess the rate of anti‐rotavirus vaccination in celiac patients from the Spanish REPAC2 national registry in comparison to the vaccination rate of their corresponding cohort based on year and place of birth.

Methods: The frequency of anti‐rotavirus vaccination was compared among celiac patients under 15 years old diagnosed between 2011 and 2017, included in the national multicenter REPAC2 registry (n=3556). They were grouped by year of birth and autonomous community. The vaccination frequency within these groups was juxtaposed with the vaccination rate in the general population born in the same years and autonomous communities, calculated based on birth data from the National Institute of Statistics and vaccine distribution in the different Spanish Autonomous Communities (data provided by GSK laboratories).

Results: The percentage of vaccinated individuals among celiac patients stands at 28.7% (95% CI 27.2 to 30.2%), while the expected percentage (assuming population coverage) would be 27.7% (p=0.177, one‐proportion z‐test). The vaccinated individuals (annual %) among celiac patients (observed) versus the data in the general population (expected), grouped by year and place of birth, did not show any significant difference.

Conclusions: No differences have been observed in the rotavirus vaccination percentages between celiac patients and the general population within the same age group and spanish autonomous community

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IMMUNOLOGICAL BIOMARKERS AT BIRTH AND LATER RISK OF CELIAC DISEASE

Maria Ulnes^1,2, Susanne Lindgren^1,2,3, Karl Mårild^1,2, Veroniqa Lundbäck^4,5, Olov Ekwall^1,2,3, Rolf Zetterström^4,5

¹Department Of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden, ²Department Of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, Gothenburg, Sweden, ³Rheumatology And Inflammation Research, The Sahlgrenska Academy, Gothenburg, Sweden, ⁴Centre For Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden, ⁵Department Of Molecular Medicine And Surgery, Karolinska Institute, Stockholm, Sweden

Objectives and Study: Perinatal risk factors have been implicated in the development of celiac disease (CD), but it is unknown whether immune cell profiles in newborns are linked to later CD. We determined markers of neonatal T and B cells from newborn screening cards of children with later CD vs. matched comparators.

Methods: This study was based on 158 children with CD (median age at diagnosis 7 years, interquartile range [IQR] 5; 9) each matched with two comparators by sex, gestational age at birth and birthdate. We performed qPCR on neonatal dried blood spots (DBS) to quantify T‐cell receptor excision circles (TRECs) and kappa‐deleting recombination excision circles (KRECs) as markers of T‐ and B‐cells output, respectively. With novel epigenetic techniques we estimated the relative proportions of CD3+ T cells, CD4+ Thelper cells, CD8+ cytotoxic T cells, CD4+ memory T cells, regulatory T cells, B cells and NK cells on DBS.

Results: We found no association between a later CD diagnosis and the measured immune cell markers. For TRECs the median no. of copies were 120 (IQR 92; 168) in CD cases vs. 136 (IQR 91; 183) in comparators. The corresponding number for KRECs was 69 (IQR 45; 100) in cases vs. 66 (IQR 44; 93) copies in comparators. The median of the relative cell counts (expressed as % of lymphocytes) were for overall T cells 32.6% (IQR 27.0; 43.8%) in CD cases vs. 33.9% (IQR 26.3; 45.7%) in comparators and for B cells 25.4% (20.3; 30.6%) vs. 24.7 (19.9; 13.8%). For all lymphocyte subsets, the fold‐change (ratio between the groups means) were close to 1 (between 0.98 and 1.15, all p‐values 0.46, all 95% CI including1).

Conclusions: Based on genetic and epigenetic markers of T and B cell development, we found no evidence that immune cell profiles in newborns influence the later risk of CD.

Contact e‐mail address: mariaulnes@gmail.com

EVALUATION OF THE GROWTH HORMONE‐IGF1 AXIS AND SERUM FGF21 LEVELS AS RELATED TO STATURE IN CHILDREN WITH COELIAC DISEASE ADHERENT TO GLUTEN FREE DIET

Fırat Kaya¹, Nafiye Urgancı², Merve Kesim Usta², Ahmet Uçar³

¹Department Of Pediatrics, University of Health Sciences,Şişli Hamidiye Etfal Health Practices and Research Centre, ISTANBUL, Turkey, ²Department Of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey, ³Pediatric Endocrinology, University of Health Sciences,Şişli Hamidiye Etfal Health Practices and Research Centre, Division of Pediatric Endocrinology, Istanbul, Turkey, ISTANBUL, Turkey

Objectives and Study: Despite adherence to gluten‐free diet(GFD), short stature may persist in some patients with coeliac disease(CD). Studies investigating the growth hormone(GH)‐insulin like growth factor‐1(IGF1) axis in children with CD are scant and inconclusive. The inhibitory effects of Fibrolast growth factor21(FGF21) on GH action are direct, and may result from the reduced translocation of GH receptors from the cytoplasm to the cell membrane. Data regarding serum FGF21 levels in patients with CD are currently unavailable.

Methods: 141 consecutive patients with CD who were adherent to GFD for at least two years were enrolled in the study. Standard methods were used for current anthropometric measurements and pubertal staging. Fasting blood samples for serum IGF1, IGFBP3 and FGF21 levels were drawn. Patients with height standard deviation(SD)1.5 SD below target height (TH) underwent GH stimulation tests(clonidine and L‐dopa). Comparisons of clinical and laboratory data of patients with height SD within range of TH and those below TH were performed. Significance was granted for p < 0.05.

Results: Sixteen(11.3%) patients had short stature, i.e. height SD< ‐2 and 21(14.9 %) patients had body mass index SD<‐2. Of the 12(8.5%) patients with height SD<1.5 SD of TH,3(2.1%) patients had GHD. Serum IGF1 SD and IGFBP3 SD were significantly higher in patients with height SD within TH than those with height SD below TH and without GHD(P=0.009 and 0.002; respectively). Serum FGF21 levels in patients with height SD within TH and those with height SD belowTH were not different(P=0.765). Serum FGF21 levels were not significantly correlated with any of the clinical and laboratory variables investigated in the study (P>0.05for all).

Conclusions: The frequency of GHD in our cohort was 2.1%. The lower IGF1 and IGFBP3 levels in non‐GHD patients below TH may suggest GH resistance. Serum FGF21 levels were not associated with stunted growth in our cohort.

Contact e‐mail address: firatkaya9296@gmail.com

AGE‐SPECIFIC CHANGES IN GUT MICROBIAL DIVERSITY IN CYSTIC FIBROSIS: A META‐ANALYSIS

Blanka Bódy^1,2, Regina Molnár^1,2, Réka Tóth¹, Tamás Kói¹, Klementina Ocskay², Andrea Párniczky^2,3

¹Semmelweis University, Centre for Translational Medicine, Budapest, Hungary, ²Heim Pál National Pediatric Institute, Budapest, Hungary, ³Institute For Translational Medicine, University of Pécs, Medical School, Pécs, Hungary

Objectives and Study: Intestinal flora in patients with cystic fibrosis (pwCF) is severely disrupted and a potential source of further complications. We aim to provide quantitative evidence of the differences in gut microbiota between pwCF and non‐CF controls to understand CF gut flora composition and identify potential sites for microbiota modulation.

Methods: We conducted a systematic review and meta‐analysis of PubMed, EMBASE, CENTRAL, Web of Science, and Scopus up to November 13, 2023. (CRD42023482792). Full‐texts of case‐control studies reporting gut microbial alpha or beta diversity or abundance of pwCF and controls with no condition or drugs affecting gut microbiota were selected. Standarized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random effects model for alpha diversity measures. Subgroup analysis for infants, children and adults was performed.

Results: Among 2552 studies, 13 (1340 participants) met inclusion criteria. Meta‐analysis revealed significant differences in alpha diversity between pwCF and controls for Shannon's index (SMD= ‐0.67; 95% CI ‐1.12 to ‐0.13; p=0.02), ChaO1 index (SMD= ‐1.32; 95% CI ‐1.44 to ‐1.2; p<0.001), and observed OTUs (SMD= ‐1.26; 95% CI ‐2.12 to ‐0.39; p=0.013). Subgroup analysis by age showed significant differences in children for Shannon and ChaO1 indexes, in adults for Shannon index, but not in infants (Table 1). Gut microbiota diversity is significantly reduced in pwCF, marked by decreased abundance of Bacteroidetes, Ruminococcaceae, Roseburia, Bifidobacterium, and increased Enterococcus, Veillonella, and Enterobacter, however not present in infants with CF.

Conclusions: The reduced diversity in CF gut microbiota, characterized by specific taxa alterations highlights potential targets for therapeutic interventions. Age‐specific microbial dynamics warrant further investigations to tailor precise interventions for different age groups within the CF population.

Contact e‐mail address: blanka.rebeka.body@gmail.com

LONG‐TERM EFFICACY OF DUAL CFTR MODULATORS ON BODY MASS INDEX, BODY COMPOSITION, AND FECAL ELASTASE LEVELS IN CHILDREN WITH CYSTIC FIBROSIS: A REAL‐WORLD COHORT ANALYSIS

Marcell Imrei^1,2, Adrienn Kéri², Éva Gács², Éva Kosaras³, Csaba Péterfia⁴, Klára Vass⁵, Székely Gyöngyi⁶, Klementina Ocskay², Andrea Párniczky^2,7

¹Medical School, University of Pécs, Pécs, Hungary, ²Heim Pál National Pediatric Institute, Budapest, Hungary, ³Velkey László Gyermekegészségügyi Központ, Miskolc, Hungary, ⁴Department Of Paediatrics, University of Pécs, Pécs, Hungary, ⁵Szabolcs‐Szatmár‐Bereg Vármegyei Oktatókórház, Nyíregyháza, Hungary, ⁶Mosdósi Telephely, Somogy Vármegyei Kaposi Mór Oktató Kórház, Mosdós, Hungary, ⁷Institute For Translational Medicine, Medical School, University of Pécs, Pécs, Hungary

Objectives and Study: Short‐term efficacy of dual cystic fibrosis transmembrane conductance regulator (CFTR) modulators are clearly presented in clinical trials, data on long‐term extrapulmonary effectiveness is limited. This prospectively collected cohort assessed real‐world outcomes of F508del‐hom*ozygous people with cystic fibrosis (pwCF), up to 2 years after the introduction of lumacaftor/ivacaftor (LUM/IVA) therapy.

Methods: Data between 2021‐2023 were retrieved from Heim Pál National Pediatric Institute medical records. Body mass index (BMI) Z‐score, body composition (measured by Inbody 770) and fecal elastase‐1 values were analyzed. Data are presented as median and IQR, p‐value calculated using paired t‐test.

Results: Data of 49 pwCF (43% female, median age 9.3 years (IQR:5.5‐14.1)) were analyzed. BMI Z‐score increased from ‐0.85 (IQR:‐1.37‐0.48) to ‐0.46 (IQR:‐0.96‐‐0.05), with a p‐value of 0.660. Within the population, BMI z‐scores showed a notable normalization trend. Children with lower initial BMI exhibited increased BMI z‐scores, while those with higher initial BMI experienced reductions during therapy. Body composition analysis showed negligible changes in muscle mass percentage from 43% (IQR:39‐47) to 42% (IQR:40‐49), body protein content from 17% (IQR:16‐18) to 17% (IQR:15‐18%) and water content from 63% (IQR:59‐66) to 62% (IQR:57‐65), contrasting with a significant (p=0.012) increase in body fat content from 11% (IQR:9‐17) to 15% (IQR:12‐22), with an even more impressive 2‐fold increase in the under‐12 age group from 8% (IQR:3‐11) to 19% (IQR:15‐25). At the start of therapy, only one patient was pancreatic exocrine sufficient (PES) (fecal elastase >200ug/g), the others had elastase levels below 100ug/g. After 2 years, two pwCF had PES and 2 other had elastase levels between 100‐200ug/g.

Conclusions: The results of the body composition examination nuance the beneficial effects of dual CFTR modulator therapy on body weight, and suggests that the increase in body weight is almost entirely the result of an increase in fat mass. Fecal elastase levels suggest an improvement in exocrine pancreas function.

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SCHWACHMAN‐DIAMOND SYNDROME IN PAEDIATRIC AGE: EXPERIENCE OF A NATIONAL REFERRAL CLINIC

Alessandra Mari¹, Philip Ancliff², Kezia Kite³, Eleanor Constant⁴, Jutta Kӧglmeier¹

¹Paediatric Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust London, London, United Kingdom, ²Paediatric Haematology, Great Ormond Street Hospital for Children NHS Foundation Trust London, London, United Kingdom, ³Dietetics, Great Ormond Street Hospital, JH, United Kingdom, ⁴Paediatric Psychology, Great Ormond Street Hospital for Children NHS Foundation Trust London, London, United Kingdom, London, United Kingdom

Objectives and Study: Exocrine pancreatic insufficiency (EPI), skeletal abnormalities and bone marrow dysfunction are characteristic for Schwachman‐Diamond syndrome (SDS). We aimed to describe phenotypic presentations in children.

Methods: All patients attending a national SDS clinic (1991‐2023) were included. Retrospective data collection included: symptoms, genetics, radiological/laboratory testing.

Results: 54 patients (27/54; 50% female) were identified. 45/54 (83,3%) had SBDS mutations; 22/54 (40,7%) compound heterozygous. 12/54 (22,2%) presented as neonates; median age at symptoms onset was 3,5 (1‐7) months; median age at diagnosis was 13 months (1‐3 years). Most presented with failure to thrive (24/54; 44,4%). The majority developed hematological abnormalities: 44/54 (81,5%) neutropenia, 13/54 (24%) anemia, 19/54 (35,2%) thrombocytopenia, 5/54 (9,2%) pancytopenia. 5/54 (9,2%) patients required G‐CSF. 4/54 (7,4%) patients underwent bone marrow transplantation (BMT). 7/54 (13%) patient died, 3 post BMT. Mild transaminitis occurred in 18/54 (33,3 %), 2/54 (3,7%) presented with acute liver failure, which resolved spontaneously. 44/54 (81,5%) had exocrine pancreatic insufficiency; pancreatic ultrasound showed fatty infiltration in 21/54 (38,8%); pancreatic function recovered spontaneously in 6/54 (11,1%). 23/54 (42.6%) had skeletal abnormalities; 2/54 severe (1/54 thoracic dysplasia, 1/54 radial aplasia). Also common were dental abnormalities (19/54; 35,2%), impaired neurodevelopment (20/54; 37%) and eczema (14/54; 26%). 28/54 (51,9%) had micronutrient deficiencies. Rarer findings included hearing impairment (4/54; 7,4%), cleft palate (3/54; 5,5%), retinal abnormalities (2/54; 3,7%). Severe tracheomalacia, complex urinary malformation, glomerulonephritis, hydrocephalous, immune thrombocytopenic purpura requiring splenectomy were reported in single patients. Auxology revealed 12/54 (22,2%) patients had a weight below 2^nd centile, 7/54 (13%) had height below 2^ndcentile; 2/54 (3,7%) had growth hormone deficiency. 11/54 (20,3%) required tube feeding in infancy, 1/54 inpatient parenteral nutrition in the neonatal period.

Conclusions: SDS presents with a variable phenotype. Whilst most patients presented with the classical symptoms triad some features reported in our cohort were not previously described.

Contact e‐mail address: alessandra.mari@unimi.it

FECAL CALPROTECTIN LEVELS IN PEDIATRIC ACUTE PANCREATITIS

Salah Mahamid¹, Noy Lapidot², Noam Zevit², Michal Rozenfeld Bar Lev², Ari Silbermtz², Dror Shouval², Raanan Shamir², Manar Matar²

¹Department Of Pediatrics, Schneider Children's Medical Center of Israel, Petach Tikva, The Sackler Faculty of Medicine, Tel Aviv University,Israel, Petach Tikva, Israel, ²The Institute Of Gastroenterology, Nutrition And Liver Diseases, Schneider Children's Hospital, Petach‐Tikva, Israel, The Sackler Faculty of Medicine, Tel Aviv University,Israel, Petach Tikva, Israel

Objectives and Study: Fecal calprotectin (FC) is increased in patients with active inflammatory bowel disease (IBD) and is a useful objective marker for follow up. It is not known whether FC levels are increased in acute pancreatitis (AP), which can sometimes present as the first manifestation of IBD. We aimed to define FC levels in AP and the natural history of AP and FC levels.

Methods: The medical records of pediatric patients that were admitted with AP between 2015‐2022 were reviewed, including demographic characteristics, clinical outcome, laboratory data, pancreatic and biliary tree imaging findings and FC levels. Patients with elevated FC (>100 mcg/g stool) were assessed for a second FC measurement after 6 weeks.

Results: Fifty four patients were admitted with AP during the study period, and 39 (72%) patients had FC measured at time of presentation (20 [52%] females, age 10[IQR5.6‐14.7] years). The median FC level was 58 (IQR 16.5‐210) mcg/g stool; Seventeen patients (44%) had an elevated FC>100 mcg/g stool. Normalization of FC occurred in 5/17 patients (29%) in a median time of 8.5 (IQR 12‐4.5) months. Five of 17 (29%) were diagnosed with subsequent IBD within a median time of 8 (IQR 2.6‐35.5) months. Additional 5 patients (29%) developed subsequent recurrent pancreatitis, related to anatomic abnormalities in 3/5. Three subjects out of 22 (14%) who had normal FC at time of AP presentation, developed IBD later at a median time of 15(IQR4.3‐37) months.

Conclusions: FC should be obtained in patients presenting with AP, and during follow up. Elevated FC may indicate that AP is associated with IBD, though follow up levels are indicated also in those with normal FC at presentation.

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CHRONIC PANCREATITIS IN CHILDREN ‐ REPORT OF 524 CASES

Grzegorz Oracz¹, Agnieszka Rygiel²

¹Dep. Of Gastroenterology, Hepatology, Feeding Disorders And Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland, ²Department Of Medical Genetics, National Research Institute of Mother and Child, Warsaw, Poland

Objectives and Study: Chronic pancreatitis (CP) is of a rare occurrence in childhood. The etiology of CP in children is varied and includes anatomic anomalies, gene mutations, metabolic disorders and others. Objective: The aim of this study was to investigate the etiological aspects of CP in children from well‐defined hom*ogenous single‐centre cohort.

Methods: Materials and Methods: 524 children with CP (aged: 0.2‐18 years; mean 8.7 years; F‐274, M‐250) hospitalized between 1998 and 2023 were enrolled into the study. The diagnosis of CP was established according to INSPIRE recommendations. Clinical and epidemiological data were recorded and analyzed. All patients were screened for mutations in the high‐risk genes associated with CP. All children had preceding imaging studies.

Results: Gene mutations were found in 340 children (65%) (SPINK1 mutation in 152 children, CTRC in 122 patients, CFTR in 77 patients, PRSS1 in 68 children, TRPV6 in 17, CEL‐HYB in 9 and CPA1 in 5; 83 pts (17.1%) have 2 or more mutations. Anatomic anomalies of pancreatic duct were diagnosed in 94 patients (18%) (59‐ pancreas divisum, 16‐ ansa pancreatica, 10‐ ABPU, 3‐ two main pancreatic ducts, 6‐other). Toxic‐metabolic risk factors were found in 65 children (14.9%). Hyperlipidemia was present in 46 patients (9.5%), including isolated in 18 patients (3.7%) and coexisting with obesity/metabolic syndrome in 28 (5.8%). Chronic renal failure was present in 4 (1%), mitochondrial cytopathies in 3 (0.6%) and hypercalcemia (hyperparathyroidism) in 2 (0.5%) patients with CP. CP was associated with biliary tract diseases in 55 patients (10%). Autoimmune pancreatitis was diagnosed in 22 children (3.7%). Idiopathic CP was diagnosed in 38 children (7%).

Conclusions: Conclusions: 1. The most common etiologic factors of chronic pancreatitis in children are gene mutations and anatomic anomalies of pancreatic duct. 2. CP is a multifactorial disease. 3. Our data demonstrate the need for genetic testing in children with chronic pancreatitis.

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CLINICAL PRESENTATION, TREATMENT AND FUTURE OF CHILDREN WITH PRIMARY INTESTINAL LYMPHANGIECTASIA

Noémie Goret¹, Aurélie Sabard¹, Cécile Lambe², Emanuelle Dugelay³, Alexandre Fabre⁴, Béatrice Dubern⁵, Pierre Poinsot⁶, Alain Dabadie⁷, Haude Clouzeau⁸, Jean Pierre Hugot³, Stephanie Willot¹

¹CHU, Tours, France, ²CHU Necker, Paris, France, ³CHU Robert Debré, Paris, France, ⁴CHU, marseille, France, ⁵CHU Trousseau, Paris, France, ⁶CHU, Lyon, France, ⁷Department of Pediatrics, INRAE, INSERM, Univ Rennes, Nutrition Metabolisms et Cancer, NuMeCan,, Rennes, France, ⁸CHU, Bordeaux, France

Objectives and Study: Primary intestinal lymphangiectasia (PIL) is a rare disease responsible for protein‐losing enteropathy. The evolution and follow‐up of these patients are poorly described in the literature. The main objective of this study is to describe the clinical presentation, the treatments implemented and the future of patients from a national cohort. The secondary objective is to define at the time of diagnosis the characteristics that can be predictive of complete response under fat‐free diet.

Methods: We conducted a national retrospective study including children with PIL followed in France between January 2010 and January 2022 in Maladie Rares Digestives (MaRDI) centers

Results: Thirty‐four children were included; the median age at diagnosis was 7 months (1 month‐16 years). Extremities edema (79%), chronic diarrhea (50%) and ascites (35%) were the main symptoms. Thirty‐one patients received the low‐fat diet with a response (disappearance of symptoms and no need for albumin infusion) for 25 (74%) of them. The median follow‐up duration in our cohort was 4,5 years (1‐23). Fifteen patients (60%) had a partial response (persistence of hypoalbuminemia < 35g/L) and 10 patients (40%) had a complete response (normalization of albuminemia). Three patients had mildly symptomatic forms that did not require therapeutic management. The normal diet has been reintroduced in 9 patients with complete response (considered cured) and 5 patients with partial response. Albuminemia was stable without infusion and there was no impact on growth. The presence of lymphedema or an identified genetic mutation were predictive factors of an absence of complete response to diet (p < 0.05).

Conclusions: This is the first description of a French national cohort of children with primary intestinal lymphangiectasia and the largest cohort published yet. Seventeen patients (50% of the cohort) were on a normal diet at the end of the study.

Contact e‐mail address: 1

DUPILUMAB IMPROVES DISEASE SEVERITY AND QUALITY OF LIFE IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS: 52‐WEEK RESULTS FROM THE PHASE 3 EOE KIDS TRIAL

Evan Dellon¹, Salvatore Oliva², Dhandapani Ashok³, Ruiqi Lui⁴, Lila Glotfelty⁵, Arsalan Shabbir⁴, Sarette Tilton⁵, Wenzhen Ge⁴

¹University of North Carolina School of Medicine, Chapel Hill, United States of America, ²Pediatric Gastroenterology And Liver Unit, Maternal And Child Health Department, Sapienza – University of Rome, Rome, Italy, ³Western University, London, Canada, ⁴Regeneron Pharmaceuticals Inc., Tarrytown, United States of America, ⁵Sanofi, Bridgewater, United States of America

Objectives and Study: Dupilumab is approved in the US/EU for eosinophilic esophagitis (EoE) treatment in patients aged ≥12 years, weighing ≥40 kg. There are no approved EoE treatments in patients aged <12 years. This analysis assessed the impact of higher‐exposure dupilumab or placebo on caregiver‐/clinician‐/patient‐reported disease severity, and caregiver/patient quality of life (QoL), in patients aged 1 to <12 years in the Phase 3 EoE KIDS trial through week (W)52.

Methods: EoE KIDS included a 16‐W, double blind, placebo‐controlled treatment period (Part A) and a 36‐W active treatment extension (Part B). The Pediatric EoE Impact Scale measures EoE impact on QoL in patients aged ≥8 to <12 years and caregivers (PEIS‐P/PEIS‐C). Global Impression of Severity and Change (GIS/GIC) measure, respectively, severity, and EoE status, reported by patients aged ≥8 to <12 years (GIS‐P/GIC‐P), caregivers (GIS‐C/GIC‐C), and clinicians (GIS‐Clin/GIC‐Clin).

Results: Baseline characteristics were balanced between groups, except PEIS‐P score (placebo, 0.5; higher‐exposure dupilumab, 0.9). At W16, caregivers’ and patients’ QoL numerically improved from baseline with higher‐exposure dupilumab vs placebo (Table). Additionally, mean change in GIS‐C/Clin/P scores showed greater numerical improvement with higher‐exposure dupilumab vs placebo at W16. GIC‐C/Clin/P assessments also showed greater numeric improvements in overall EoE status with higher‐exposure dupilumab vs placebo at W16. At W52, improvements were maintained in QoL, EoE severity and overall EoE status with continuous higher‐exposure dupilumab, and improvements were also seen in those who switched from placebo to higher‐exposure dupilumab at W16. Lower‐exposure dupilumab patients also maintained improvements in the aforementioned measures through W52 with comparable/numerically lower effects than with higher‐exposure dupilumab.

Conclusions: Higher‐exposure dupilumab led to numeric improvements in reported EoE status/severity, and patients’/caregivers’ QoL, adding to significant histologic/endoscopic/transcriptomic improvements in EoE with higher‐exposure dupilumab; together these data provide a holistic view of improvements.

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VALIDATION OF A NEW 30‐MINUTE COILED OESOPHAGEAL STRING TEST (CEST) WITH ENDOSCOPY FOR ASSESSMENT AND MONITORING OF CHILDREN WITH EOSINOPHILIC OESOPHAGITIS (EOE)

Elise Peever¹, Nadeem Afzal², Efrem Eren³, Michel Erlewyn‐Lajeunesse⁴, Vinod Kolimarala⁵, Mark Alderton⁶, Ann‐Marie Jones⁷, Hamza Afzal⁸

¹Paediatric Gastroenterology, Southampton Children's Hospital, YD, United Kingdom, ²Department of Paediatric Gastroenterology, Southampton Children's Hospital and, University of Portsmouth, Southampton, United Kingdom, ³Clinical Immunology, University Hospital Southampton, YD, United Kingdom, ⁴Southampton Children's Hospital, YD, United Kingdom, ⁵Paediatric Gastroenterology, Maidstone and Tunbridge Wells NHS Trust, QQ, United Kingdom, ⁶Paediatric Allergy, Southampton Children's Hospital, YD, United Kingdom, ⁷Dietetics, Southampton Children's Hospital, YD, United Kingdom, ⁸Cardiff University, AT, United Kingdom

Objectives and Study: To assess the validity of a novel string testing method using Eosinophil Cationic Protein (ECP) as a biomarker, comparing it to traditional histologic eosinophil counts in children suspected of having EoE.

Methods: In this single‐centre study, consecutive recruitment was performed by a single clinician over two years, recruiting children with symptoms suggestive of EoE. 34 patients underwent both the string test and endoscopy (EREFS grading), with histological assessment and eosinophil counts in 3 level oesophageal biopsies.

Results: Of the 34 patients presenting with symptoms of reflux and dysphagia, 14 were diagnosed with EoE based on the (ESPGHAN) criteria for diagnosing EoE (eosinophil biopsy count >15). The youngest child was 6.86 years old and there was a male predominance (76.5%). A significant correlation (Pearson Rank 0.6, p<0.001) was observed between ECP levels and histological eosinophil counts. The ROC curve for ECP indicated an Area Under Curve (AUC) of 0.891. Macroscopic endoscopic findings such as oesophageal exudates, rings and furrows were predictive of active EoE (p<0.1). ECP levels correlated with the macroscopic presence of exudates and furrows, but not with oesophageal rings or edema. Neither IgE levels nor eosinophil counts predicted ECP levels.

Conclusions: The string test using ECP as a biomarker demonstrated safety, and a good correlation with oesophageal eosinophil counts, rendering it a promising tool in the management of children with EoE. This non‐invasive approach could be cost effective and offer a viable alternative to conventional invasive endoscopy in the ongoing assessment and monitoring of paediatric EoE.

Contact e‐mail address: elise.peever1@nhs.net

GUTMICROBIAL AND METABOLIC FEATURES ASSOCIATED WITH CLOSTRIDIOIDES DIFFICILE INFECTION RECURRENCE IN CHILDREN

Xiaolu Li, Fangfei Xiao, Yizhong Wang, Xufei Wang, Lin Ye, Ting Zhang

Department Of Gastroenterology, Hepatology, And Nutrition, Shanghai Children's Hospital, Shanghai, China

Objectives and Study: Recurrent Clostridioides difficile (C. difficile) infection (rCDI) is a critical clinical issue for the increasing incidence and difficulty in treatment. We aimed to identify gut microbial and metabolic features associated with disease recurrence in a group of pediatric CDI patients.

Methods: A total of 84 children with primary CDI were prospectively enrolled in the study. Fecal samples collected at the initial diagnosis were subjected for 16S rRNA gene sequencing and targeted metabolomics analysis to profile the bacterial composition and metabolome.

Results: Twenty‐six (26/84, 31.0%) pediatric CDI patients experienced recurrence. The alpha diversity of fecal microbiota was significantly lower in the recurrers, and the beta diversity was separate from that of non‐recurrers. Taxonomic profiles showed that the relative abundances of multiple bacterial taxa were significantly differed between recurrers and non‐recurrers. Linear discriminant analysis (LDA) effect size (LEfSe) analysis identified several bacterial genera that discriminated the recurrers and non‐recurrers, including Parabacteroides, Coprococcus, Disalister and Clostridium. Recurrers exhibited lower abundances of several short‐chain fatty acids (SCFAs)‐producing bacteria (Faecalibacterium, Butyricicoccus, Clostridium, Roseburia, and Ruminococcus), which were correlated with reduced fecal SCFAs levels. In addition, several bile acids (BA), including lithochalic acid (LCA), 12‐KetoLCA, trihydroxycholestanoic acid (3‐DHCA), and deoxycholic acid (DCA) were decreased in recurrers.

Conclusions: Our study suggests that the differed gut microbiota in pediatric CDI patients may contribute to disease recurrence by modulating SCFA concentrations and BA profiles. The gut microbiota and metabolites signatures may be used to predict disease recurrence in CDI children.

Contact e‐mail address: zhangt@shchildren.com.cn

ASSESSMENT OF ANORECTAL FUNCTION USING HIGH RESOLUTION ANORECTAL MANOMETRY IN HEALTHY CHILDREN

Natalia Bilińska, Barbara Skowronska, Aleksandra Banaszkiewicz, Marcin Banasiuk

Department Of Paediatric Gastroenterology And Nutrition, Medical University of Warsaw, Warsaw, Poland

Objectives and Study: Anorectal manometry (AM) is a gold standard test to assess the functional disorders of the lower gastrointestinal tract (constipation, fecal incontinence) and anorectal functions in patients with congenital defects. In paediatric population reference values have been established for 3 D catheter (newborns and older children) and for water‐perfused (infants). There is lack of normative data for commonly used HR solid‐state anorectal catheter in children. Therefore our aim was to assess the parameters of high‐resolution anorectal manometry (HRAM) using solid state probe.

Methods: Patients aged 1‐18 years were qualified for the study. AM was performed using a Solar GI probe and performed in accordance with the London protocol. The following parameters were established: mean anal‐resting‐pressure (ARP), anal canal length (ACL), squeeze (S), squeeze pressure increase (SPI), duration of squeeze, maximum rectal pressure (MRP), push relaxation, rectoanal inhibitory reflex (RAIR), first sensation volume (FSV), defecatory volume (DV), maximum tolerated volume (MTV), receptivity, cough pressure increase. The whole cohort was divided into 3 groups related to their age: A (1‐5 y), B (6‐10y), C (11‐18y). Values are expressed as medians and interquartile range (IQR)

Results: 59 children (36 males; age 4‐17 years, mean: 7 years) were studied. Mean RP and S were 74 (33‐106) mmHg and 141 (80‐241) mmHg, respectively. Mean SPI was 132 (41‐341) mmHg. The mean ACL was 3,1 (1,6‐4,1) cm. The FSV, DV and MTV were observed at 50 (10‐120) ml, 80 (10‐160) ml and 120 (10‐200) ml of the ballon volume respectively. RAIR was observed in all children. Among the parameters assessed the ACL, MRP and MTV were significantly different between age groups (p<0.0001, p<0,004 and p<0,049 respectively).

Conclusions: HRAM normative values were established for children aging from 1 to 18

Contact e‐mail address: natalia.czyzniejewska@gmail.com

NOCTURNAL INFANT CRYING EVALUATION (NICE) STUDY: LOOKING FOR A HALLMARK OF REFLUX DISEASE IN INFANTS

Greta Carabelli^1,2, Ivan Binotto^1,2, Chiara Armano², Lorenza Bertù¹, Chiara Luini², Massimo Agosti³, Silvia Salvatore³

¹University of Insubria, Varese, Italy, ²Pediatric Department, Hospital “F. Del Ponte”, Varese, Italy, ³Department Of Paediatrics, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy

Objectives and Study: Empirical proton‐pump‐inhibitors (PPI) are often prescribed in infants for persistent crying, especially at night. The aim of this study was to identify predictive factors for pathological gastroesophageal reflux (GER) in infants with unexplained persistent crying.

Methods: We consecutively enrolled all infants (0‐12months) referred to our center in the last 15 years to perform esophageal impedance pH‐monitoring (MII‐pH) for unexplained persisting crying not improved with parental education, dietary advices, special infant formulas, and alginate treatment. We excluded infants with gastrointestinal malformation/surgery, neurological impairment, infections. Demographic and growth parameters, GER symptoms, presence of nocturnal crying, I‐GERQ‐R score, previous treatments and all MII‐pH parameters (including total and nocturnal basal impedance) were recorded and analyzed. Since the cut‐off for pathological acid reflux index in neonates and infants is still controversial, in accordance with ESPGHAN guidelines for GER, we considered completely normal MII‐pH when all the following were present: reflux index <3%; symptom index for crying <50%; symptom association probability <95%. Statistical analysis was performed using Chi‐Square, Univariate and Multivariate analysis (Anova).

Results: We recruited 50 infants (median age 4 months, 24 male): 30 (60%) infants had normal MII‐pH results. I‐GERQ‐R score was abnormal in 33 (66%) infants, 21 (64%) had normal MII‐pH (p 0.47). In the 26 (52%) infants reporting nocturnal crying, MII‐pH was normal in 16 (54%) (p 0.82). The additional presence of regurgitation (> 3 episodes/die or >10/die) did not significantly predict the results of MII‐pH (p 0.74 and p 0.82, respectively). The univariate analysis of all clinical and MII‐pH variables found a significant correlation only between abnormal MII‐pH and total‐mean‐basal‐impedance (p 0.02). However, a multivariate analysis showed any significant association.

Conclusions: Infants with persistent unexplained crying and nocturnal crying do not show any distinctive clinical features predictive of abnormal MII‐pH. Empirical PPI should not be started in this population.

Contact e‐mail address: gcarabelli2@studenti.uninsubria.it

RISK FACTORS FOR DEVELOPMENT OF FUNCTIONAL GASTROINTESTINAL DISORDERS IN THE FIRST YEAR OF LIFE: A COHORT STUDY

Arianna Aceti¹, Isadora Beghetti¹, Flavia Marchese², Matteo Rinaldi³, Gianfranco Maffei³, Roberta De Benedetto², Assunta Grillo², Flavia Indrio⁴

¹University of Bologna, Bologna, Italy, ²Department of Medical and Surgical Science, Pediatric Section, University of Foggia, Foggia, Italy, ³Department of Neonatology and NICU, Ospedali Riuniti Foggi, Foggia, Italy, ⁴University of Salento, Lecce, Italy

Objectives and Study: To identify neonatal risk factors for Functional Gastrointestinal Disorders (FGIDs) development and to assess the prevalence of colic, regurgitation, and constipation in the first year of life. A prospective multicentre area‐based cohort study, including preterm and term neonates consecutively enrolled at birth, was performed.

Methods: Neonatal characteristics, hospitalization, maternal and paternal history of smoking, FIGIDs diagnosis, were assessed at birth and at follow‐up visits.

Results: Out of 9.500 newborn born between January 1^st, 2020 and December 31^st, 2022, 6060 were enrolled. 469 (7,7%) were born preterm. Prevalence of FGIDs in infants born preterm was significantly higher compared with infants born full term (infantile colic 39.4% vs. 26.3%, p < 0.001; regurgitation 36.0% vs. 17.2%, p < 0.001; functional constipation 22.2% vs. 9.2%, p< 0.001). Different multivariate analyses were performed for term and preterm infants. In term infants, neonatal antibiotics and low cord blood pH were associated with infantile colic, regurgitation and functional constipation (p <0.001); NICU hospitalisation was significantly associated with regurgitation (p<0.001); paternal smoking was significantly associated with infantile colic (p < 0.001) while maternal smoking with regurgitation and constipation (p<0.01). Exclusive breastfeeding at discharge was associated with a lower risk of FGIDs (p <0.001). In preterm infants, neonatal antibiotics and paternal smoking were significantly associated with infantile colic (p < 0.05); NICU hospitalisation and twin pregnancy were significantly associated with regurgitation (p< 0.01).

Conclusions: Preterm infants have a higher risk of FGIDs in the first year of life compared to term infants. In term infants neonatal use of antibiotics, low cord blood pH and parental smoking are independently associated with FGIDs while exclusive breastfeeding at discharge appear to be a protective factor. The identification of risk and protective factors may be important to select children who will develop this condition and implement a preventive approach. Further research is warranted.

Contact e‐mail address: flaviaindrio1@gmail.com

SLEEP QUALITY AND SOCIAL EMOTIONAL ASSESSMENT IN CHILDREN AGED 3‐36 MONTHS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS

Ali Can Bayraktar¹, Ozlem Kalaycik Sengul², Sebahat Cam³

¹General Pediatrics, Medeniyet University Faculty of Medicine, Istanbul, Turkey, ²Pediatric Gastroenterology, Medeniyet University, Istanbul, Turkey, ³Pediatric Gastroenterology, Hepatology And Nutrition, Medeniyet University Faculty of Medicine, Istanbul, Turkey

Objectives and Study: The aim was to evaluate sleep quality in children with FGID aged 3 to 36 months, as well as to make a social emotional assessment in children with FGID aged 12 to 36 months.

Methods: Children aged 3‐36 months with FGID formed the study group, healthy children of the same age were taken as the control group. All patients were analyzed for demographic data and growth parameters. ‘Brief Infant Sleep Questionnaire’ (BISQ) was administered to all chidren and ‘Brief Infant Toddler Social Emotional Assessment’ (BITSEA) was administered to infants aged 12‐36 months.

Results: Sixty‐three children with FGID and 81 healthy children were included in the study. Of these, 25 (39.6%) had infant regurgitation, 20 (31.7%) had functional constipation, 13 (20.6%) had infantile colic, 10 (15.8%) had dyschezia, 3 (4.7%) had rumination and 2 (3.1%) had functional diarrhea. The mean age of children with FGID (9,4±7,7 months) was lower than that of children without FGID (14,8±9,2 months) (p<0.001). The frequency of sleep problems was higher in children with FGID (p=0.028). The presence of social and emotional subclinical problems was significantly higher in those with sleep problems (p=0.034). Daytime and total sleep time in patients with social and emotional subclinical problems were found to be significantly shorter than in children without such problems (p=0.026, p=0.010, respectively).

Conclusions: In our study sleep disorders were detected significantly more common in infants with FGID. Social emotional subclinical problems were found to be higher in children with sleep disorders. Studies in older children reported that sleep disorders are more common in FGID but there is no data in the literature in infants and small children. Our study may raise awareness about sleep problems in children with FGID.

Contact e‐mail address: kalaycikoz@yahoo.com

EXPLORING PALMITOYLETHANOLAMIDE AND POLYDATIN IN TREATING PEDIATRIC IRRITABLE BOWEL SYNDROME: A MULTI‐CENTER RANDOMIZED CONTROLLED TRIAL

Maurizio Mennini¹, Luca Bernardo², Cesare Cremon³, Giovanni Barbara³, Enrico Felici⁴, Melania Evangelisti¹, Silvia Furio¹, Marisa Piccirillo¹, Livia Lucchini¹, Giovanna Quatrale¹, Flaminia Coluzzi⁵, Angela Mauro², Clelia Di Mari², Pasquale Parisi¹, Giovanni Di Nardo¹

¹Nesmos Department, Sapienza University of Rome, Pediatric Unit, Sant'Andrea University Hospital, Rome, Italy, ²Department Of Childhood And Developmental Medicine,, Pediatric Unit, Fatebenefratelli‐Sacco Hospital, Milan, Italy, ³Department Of Medical And Surgical Sciences,, University of Bologna and IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy., Bologna, Italy, ⁴Pediatric And Pediatric Emergency Unit,, "Umberto Bosio" Center for Digestive Diseases, The Children Hospital, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy, ⁵Unit Of Anaesthesia, Intensive Care And Pain Medicine,, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy

Objectives and Study: This multicenter trial aimed to assess the effectiveness and safety of co‐micronized palmitoylethanolamide (PEA)/polydatin (PD) in alleviating abdominal pain symptoms among pediatric patients with Irritable Bowel Syndrome (IBS). The study sought to employ a double‐blind, placebo‐controlled, parallel‐arm design to evaluate the impact of co‐micronized PEA/PD administered over a 12‐week period on symptom severity and remission rates.

Methods: Conducted at three Italian pediatric gastroenterology centers, the study enrolled participants aged 10 to 17 years who met the Rome IV criteria for pediatric IBS. Patients were randomly assigned to receive either co‐micronized PEA/PD or placebo, administered thrice daily in a 1:1 ratio. Baseline severity was assessed using the IBS‐Severity Scoring System (IBS‐SSS) upon enrollment and at 4, 8, and 12 weeks into the treatment. Abdominal pain frequency was evaluated on a scale ranging from 1 to 7 days per week, and stool consistency was categorized using the Bristol stool scale (BSS) to identify different IBS subtypes. The primary outcome measure was the percentage of patients achieving complete remission, defined as an IBS‐SSS score < 75 points after 12 weeks of therapy.

Results: Involving 70 children with IBS, 34 received co‐micronized PEA/PD, while 36 received a placebo. The co‐micronized therapy group exhibited a significantly higher rate of patients achieving complete remission after 12 weeks compared to the placebo group (p=0.015), particularly benefiting those with the IBS‐diarrhea subtype (p=0.01). Additionally, the treatment group demonstrated notable reductions in abdominal pain intensity and frequency compared to the placebo group. No adverse events were reported throughout the study.

Conclusions: Co‐micronized PEA/PD emerged as a safe and effective therapeutic approach in alleviating abdominal pain symptoms among pediatric patients with IBS. The treatment showcased significant benefits, including a higher remission rate and improved pain management, particularly evident in the IBS‐diarrhea subtype, suggesting its potential as a promising intervention for pediatric IBS management.

Contact e‐mail address:

ASSESSMENT OF GASTRIC MOTILITY IN CHILDREN WITH FUNCTIONAL GASTROINTESTINAL DISORDERS AND SELECTED CHRONIC ORGANIC DISEASES

Tatiana Jamer, Tomasz Pytrus, Barbara Iwanczak

Department Of Paediatrics, Gastroenterology And Nutrition, Wroclaw Medical University, Wrocław, Poland

Objectives and Study: Electrogastrography (EGG) is a non‐invasive diagnostic method for recording gastric myoelectrical activity (indirectly gastric motility), using electrodes placed on the abdominal surface. EGG is indicated in FGIDs and certain organic diseases. However, the results of studies are inconclusive or even contradictory. Aim of the study: assessem*nt of gastric motility in children with FGIDs and selected organic diseases using EGG and to find characteristic and differentiating features of the EGG recording for each disease.

Methods: Children 5‐18 yo diagnosed with FGIDs or organic gastrointestinal diseases, and DM1, were enrolled. In all patients, pre‐and post‐prandial gastric myoelectric activity was recorded using a multi‐channel EGG. EGG parameters evaluated: dominant frequency and power (DF and DP), dominant frequency and power instability coefficient (DFIC and DPIC), percentage of slow wave coupling (SWC), normo‐, brady‐, tachygastria and arrhythmia.

Results: 225 children, mean age 12.8 years, 55.6% girls, were enrolled and classified into 9 groups: I‐24 with functional dyspepsia, II‐29 with IBS, III‐22 with functional abdominal pain, IV‐23 with functional constipation, V‐27 with GERD, VI‐24 chronic gastritis, VII‐27 with Crohn's disease, VIII‐26 with DM1, IX‐23 control group (without symptoms). Comparing post‐prandial gastric myoelectric activity to pre‐prandial, an increase in all EGG parameters and percentage of normogastria was observed in all groups. The pattern of change did not significantly differentiate children between groups and arrhythmia was the most common disturbance. Comparison of pre‐ and postprandial gastric myoelectric activity for all groups showed no statistically significant differences in any of the EGG recording parameters.

Conclusions: EGG did not differentiate pediatric patients with FGIDs, GERD, chronic gastritis, Crohn's disease,DM1 and healthy children. Meal stimulation improved gastric myoelectrical activity, regardless of the diagnosis. High percentage of arrhythmia and low percentage of SWC were observed in children in all groups. The role of multi‐channel EGG in pediatric gastroenterological diagnostics seems difficult to determine.

Contact e‐mail address: tatiana.jamer@umw.edu.pl

MEBEVERINE VERSUS PLACEBO IN ADOLESCENTS WITH IRRITABLE BOWEL SYNDROME OR FUNCTIONAL ABDOMINAL PAIN AND THE INFLUENCE OF LABELING: A 2X2 RANDOMIZED CONTROLLED TRIAL

Robyn Rexwinkel¹, Koen Vermeijden², Judith Zeevenhooven³, Hans Kelder⁴, Michael Groeneweg⁵, Thalia Hummel⁶, Joery Goede⁷, Herbert Van Wering⁸, Janneke Stapelbroek⁹, Marc Benninga³, Arine Vlieger²

¹Amsterdam UMC, Amsterdam, Netherlands, ²St. Antonius Hospital, Nieuwegein, Netherlands, ³Paediatric Gastroenterology And Hepatology, Amsterdam UMC, Amsterdam, Netherlands, ⁴Cardiology, St Antonius Ziekenhuis, Nieuwegein, Netherlands, ⁵Maasstad Ziekenhuis, Rotterdam, Netherlands, ⁶Medisch Spectrum Twente, Enschede, Netherlands, ⁷Spaarne Gasthuis, Haarlem, Netherlands, ⁸Amphia Ziekenhuis, Breda, Netherlands, ⁹Catharina Ziekenhuis, Eindhoven, Netherlands

Objectives and Study: Effective and safe pharmacologic treatments are lacking for children with Irritable Bowel Syndrome (IBS) and Functional Abdominal Pain – Not otherwise specified (FAP‐NOS).

Methods: In this placebo controlled, double blind, randomized trial 269 children (aged 12‐18 years old) with IBS or FAP‐NOS were assigned to mebeverine or placebo for 8 weeks and 4 weeks follow‐up. Study medication was labeled as “you may receive mebeverine or placebo” (blinded trial label) or “you receive mebeverine” (mebeverine label), thus creating four treatment groups: 1) mebeverine with a blinded trial label, 2) mebeverine with a mebeverine label, 3) placebo with a blinded trial label and 4) placebo with a mebeverine label. The primary end point was the proportion of patients who achieved treatment success (a ≥50% reduction of both abdominal pain intensity and pain frequency) after 8 weeks. The key secondary outcome measure was adequate relief of IBS/FAP‐NOS symptoms.

Results: Treatment success was similar between patients receiving mebeverine (group 1 and 2) and placebo (group 3 and 4) (23.9% vs. 23.9%, P=0.92). Significantly more patients in treatment groups with mebeverine label (group 2 and 4) achieved treatment success compared to treatment groups with blinded trial label (group 1 and 3) (32.9% vs. 15.0%, P=0.002). Similar proportions of patients receiving mebeverine (group 1 and 2) or placebo (group 3 and 4) reported adequate relief of their IBS/FAP‐NOS symptoms (43.7% vs. 47.3% P=0.52). Significant more patients in treatment groups with mebeverine label (group 2 and 4) reached adequate relief than patients in treatment groups with blinded trial label (group 1 and 3) (52.8% vs. 38.3% P=0.02).

Conclusions: Mebeverine was not superior compared to placebo for the treatment of pediatric IBS and FAP‐NOS. However, a positive drug label enhanced treatment success and adequate relief rates significantly, compared to a neutral label. This may affect the design of future pediatric trials.

Contact e‐mail address: n.k.vermeijden@amsterdamumc.nl

ACTG2D245G MUTATION CAUSE MEGACYSTIS MICROCOLON INTESTINAL HYPOPERISTALSIS SYNDROME BY IMPAIRING SMOOTH MUSCLE CONTRACTILITY

Jie Zhou¹, Shanshan Chen¹, Wei Cai^1,2,3,4,5, Yongtao Xiao^3,4, Ying Wang^1,3,4,5

¹Division Of Pediatric Gastroenterology And Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, shanghai, China, ²Department Of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, ³Shanghai Institute of Pediatric Research, Shanghai, China, ⁴Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China, ⁵Department Of Clinical Nutrition, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, shanghai, China

Objectives and Study: Megacystis microcolon intestinal hypoperistalsis syndrome is a severe congenital visceral myopathy characterized by abdominal distension due to a large non‐obstructed urinary bladder, a microcolon, and reduced or absent intestinal movements. Recent studies have shown that ACTG2 is the main gene involved in the pathogenesis of this disease. Herein, we aimed to investigate the correlation between the ACTG2^D245G mutation and disease phenotypes.

Methods: We collected clinical information from patient with ACTG2^D245G mutations. Additionally, we created a mouse model with an ACTG2^D245G mutant mouse using the CRISPR/Cas9 gene editing technology and performed spontaneous urination tests, gastrointestinal motility analysis, G‐actin/F‐actin ratio analysis, and collagen gel contraction.

Results: A proband with megacystis microcolon intestinal hypoperistalsis syndrome harbored a novel heterozygous mutation, ACTG2^D245G. ACTG2^D245G mutant mice exhibited weaker intestinal motility. The collagen gel contraction experiment demonstrated a decreased contractility of smooth muscle cells, and G‐actin/F‐actin ratio analysis revealed decreased actin polymerization. Three‐dimensional structural simulations demonstrated disrupted hydrogen bonds within the D245G mutant protein.

Conclusions: The ACTG2^D245G mutation affects intestinal motility by impairing actin polymerization and reducing cell contraction.

Contact e‐mail address:

FEASIBILITY STUDY OF A POINT‐OF‐CARE ASSAY FOR RAPID DETERMINATION OF ANTI‐TNFA BIOLOGICS IN CAPILLARY BLOOD

Leslie Anchling¹, Benjamin Ricken¹, Christian Reinhard¹, Larissa Brosi¹, Stefan Neu¹, Joana Afonso¹, Thomas Schuster¹, Christian‐Benedikt Gerhold¹, Elina Wütrich², Emanuel Burri², Anne‐Emmanuelle Berger³, Stéphane Paul³, Xavier Roblin³, Wanda Guirao³, Mathilde Barrau³, Laetitia Bastide³, Véronique Pfimlin‐Fritschy⁴, Uta Ruscher⁴, Petr Hrúz⁴

¹BÜHLMANN, Schönenbuch, Switzerland, ²Gastroenterologie, Kantonsspital Baselland, Liestal, Switzerland, ³CHU Saint‐Etienne, Saint‐Etienne, France, ⁴Claraspital Basel, Basel, Switzerland

Objectives and Study: Commercially available rapid assays allow the fast and easy measurement of Adalimumab (ADL) and Infliximab (IFX), but most of them rely on serum as analyte matrix. In order to reduce time and equipment needed, two rapid tests for the determination of ADL and IFX have been developed. They only require capillary blood (CB) or EDTA whole blood (WB) without further pre‐analytical steps. The primary aim of this study is to demonstrate matrix equivalency of CB and WB compared to serum.

Methods: Sample analysis was performed by healthcare professionals at three study sites, in a POC setting, with the established Quantum Blue® serum rapid tests and the newly developed CB applications. Blood samples from patients under infliximab therapy were collected before infusion (trough level). Samples from adalimumab‐treated patients were collected irrespective of the injection schedule. This work evaluated the interim outcome after the analysis of 29 ADL and 18 IFX patients.

Results: Bland‐Altmann analysis revealed a good agreement of CB and WB compared to serum for both IFX and ADL. A comparison of CB to serum revealed a mean bias of 5.2% for IFX and ‐11.7% for ADL. Passing‐Bablok analysis for CB versus serum resulted in a slope of 0.92 and an intercept at 0.08 for IFX, respectively 0.86 and ‐0.063 for ADL. A comparison of WB to serum revealed a mean bias of 7.8% for IFX and 7.4% for ADL. Passing‐Bablok analysis for WB versus serum resulted in a slope of 1.00 and an intercept at 0.00 for IFX, respectively 1.00 and 0.30 for ADL.

Conclusions: The rapid Quantum Blue® assays for the determination of infliximab and adalimumab in CB and WB are comparable to the analysis in serum and are well suited to be used in a POC setting, such as infusion centres.

Contact e‐mail address: lea@buhlmannlabs.ch

IS TRANSMURAL HEALING BETTER THAN MUCOSAL HEALING IN PEDIATRIC CROHN'S DISEASE?

Giulia D'Arcangelo¹, Letizia Carnevale¹, Salvatore Oliva¹, Francesca Maccioni², Giusy Russo¹, Ludovica Busato², Marina Aloi¹

¹Department Of Women's And Children's Health, Pediatric Gastroenterology And Liver Unit, Sapienza University of Rome, Rome, Italy, ²Department Of Radiological Sciences, Oncology, And Pathology, Sapienza University of Rome, Rome, Italy

Objectives and Study: Data on the long‐term benefit of transmural healing (TH) are scarce in children. We investigated the outcomes of pediatric Crohn's disease (CD) patients with TH comparing them to those with mucosal healing (MH) and with “no healing”.

Methods: Prospective, single‐center, observational study conducted at the Pediatric Gastroenterology Unit of Sapienza University of Rome. Children with an established diagnosis of CD and under biological therapy undergoing an MRE and an ileocolonoscopy within a 3‐month interval were consecutively enrolled. TH was defined as the complete healing of both the mucosa at endoscopy and of the bowel layers at the MRE. In the presence of a normal colonoscopy but an active MRE children were deemed as MH. The group “no healing” (NH) included children with an active endoscopy, regardless of the MRE classification. At 6, 12, and 24 months number disease flares, CD‐related hospitalization, CD‐related surgery, need for step‐up treatment, and occurrence of complications were collected.

Results: 93 children were included (mean age 11,2±3,8). Twenty‐three (25%) were classified as TH, 27 (29%) as MH and 43 (46%) as NH. The risk of any unfavorable outcome was lower in both TH and MH patients compared to NH (Log Rank p<0.0001 and p=0.002). Children with TH were at lower risk of hospitalization (p=0.02), and complications (p=0.007) compared to those with NH. No difference was found between MH and NH children for the same outcomes. Both TH and MH children were at lower risk of step‐up treatment (p<0.0001 and p=0.0002, respectively) compared to NH. TH and MH patients were comparable for all the outcomes evaluated.

Conclusions: Achieving TH in pediatric CD is associated with better outcomes, although the additional benefit over MH alone does not appear significant. However, the persistence of inflammation is associated with worse outcomes in all patients.

Contact e‐mail address: giuliadarcangelo87@gmail.com

HIGH SERUM LIPOCALIN‐2 EXPRESSION AT THE DIAGNOSIS IN CHILDREN WITH ULCERATIVE COLITIS: A PILOT STUDY

Giulia D'Arcangelo¹, Carla Petrella², Marco Fiore², Francesca Zucconi¹, Manuela Distante¹, Alessandro Gravina¹, Marina Aloi¹

¹Pediatric Gastroenterology And Liver Unit, Department Of Women's And Children's Health, Sapienza University of Rome, Rome, Italy, ²Institute Of Biochemistry And Cell Biology (ibbc‐cnr), Department Of Sensory Organs, Sapienza University of Rome, Rome, Italy

Objectives and Study: Lipocalin‐2 (LCN2) is a pleiotropic mediator of various inflammatory processes. We determined the serum levels of LCN‐2 in a cohort of newly diagnosed UC children, and we compared them with healthy controls.

Methods: Prospective cross‐sectional observational study conducted at the Pediatric Gastroenterology Unit of the Umberto I Hospital and at the IBBC – Institute of Biochemistry and Cell Biology – CNR in Rome. All children aged 6‐18 years of age, newly diagnosed with UC were consecutively enrolled. Blood withdrawal was conducted upon diagnosis. Human serum LCN‐2 (Cat. No. DY1757) was measured using a sandwich enzyme‐linked‐immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA), according to the protocols provided by the manufacturer. Clinical, demographic, biochemical and endoscopic data were recorded.

Results: Thirty‐two children with a new diagnosis of UC [11 (34%) female, mean age 12,7 ± 4] and 38 age‐ and sex‐matched healthy control [21 (55%) females, mean age 11.71 ± 4] were consecutively enrolled. Serum LCN‐2 levels were significantly higher in cases compared to controls (280 ± 152 ng/mL vs 66 ± 55 ng/mL), p < 0,001]. Among UC children, significantly higher LCN2 levels were measured in pancolitis (363.7± 155.2 ng/mL) compared to proctitis, left‐sided and extensive colitis (184.9 ± 74.65 ng/mL; P = 0.0003). A significant inverse correlation was observed between LCN‐2 and albumin levels at the diagnosis by the Spearman coefficient correlation (r = −0.455; P = 0.03) and a significant direct correlation was observed between LCN‐2 and CRP values at the diagnosis (r = 0.44; P <0.05).

Conclusions: Serum LCN‐2 levels are significantly higher in children with UC compared to the healthy control group, with the highest levels observed in children with the most extensive disease. Such results as well as and its correlation with the actual disease monitoring tool, make this protein an interesting candidate biomarker.

Contact e‐mail address: giuliadarcangelo87@gmail.com

PEDIATRIC INFLAMMATORY BOWEL DISEASES IN PATIENTS WITH GENETIC SYNDROMES: A CASE‐CONTROL MULTICENTRE SIGENP STUDY

Francesca Di Sario¹, Enrico Felici², Claudia Garassino², Flavio Labriola³, Branislava Cosic⁴, Licia Pensabene⁵, Pierdomenico Murone⁵, Serena Arrigo⁶, Silvana Ancona⁷, Giovanna Zuin⁸, Giacomo Colella⁸, Francesca Penagini⁹, Massimo Martinelli¹⁰, Erasmo Miele¹⁰, Maria Teresa Fioretti¹⁰, Francesco Graziano¹¹, Giulia D'Arcangelo¹², Matteo Bramuzzo¹³, Sara Lega¹³, Linda Olivetti¹, Carlo Catassi¹, Simona Gatti¹

¹Department Of Pediatrics, Università Politecnica delle Marche, Ancona (AN), Italy, ²Pediatric And Pediatric Emergency Unit,, "Umberto Bosio" Center for Digestive Diseases, The Children Hospital, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy, ³Gastroenterology Unit, Maggiore hospital, Bologna, Italy, ⁴Pediatric Post‐graduate School, Modena, Italy, ⁵Pediatric Unit, Department of Medical and Surgical Sciences, Catanzaro, Italy, ⁶Gastroenterology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy, ⁷Dipartimento Di Neuroscienze, Riabilitazione, Oftalmologia, Genetica E Scienze Materno‐infantili (dinogmi), Università degli Studi di Genova, Genova, Italy, ⁸Pediatric Department, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, ⁹Pediatric Unit, V. Buzzi" Hospital, ASST Fatebenefratelli Sacco Hospital, University of Milan, Milano, Italy, ¹⁰Section Of Pediatrics, University of Naples "Federico II", Napoli, Italy, ¹¹Pediatric Unit, Villa Sofia Cervello Hospital, Palermo, Italy, ¹²Pediatric Gastroenterology And Liver Unit, Umberto I Hospital, Sapienza University of Rome, Roma, Italy, ¹³Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy

Objectives and Study: Some genetic syndromes (GS) are associated with a risk of developing autoimmune disorders including IBD, potentially complicated by multiple comorbidities. We aimed to define the outcome of IBD in children with GS.

Methods: In this retrospective, multicenter case‐control study, we recruited IBD children with GS (group 1) and 2 matched IBD patients for each case (group 2) comparable for clinical features and follow‐up period. Monogenic VEO‐IBD were excluded. Clinical data and disease characteristics, presence of comorbidities, use of drugs and side effects, surgical outcomes and mortality were compared at diagnosis and at the last follow‐up.

Results: A total of 23 IBD children with a GS (table 1) and 46 matched controls were identified at 11 Italian pIBD units.

Thirty patients had Crohn's disease (CD) and 39 had Ulcerative Colitis (UC). The 2 groups were comparable in terms of gender, age at diagnosis (8,9±4.6 vs 9.4±4.4 years), duration of follow‐up (5.6±3.4 vs 4.1±2.9 years) and severity of disease. Diagnostic delay was longer in patients with GSs compared to controls (11,1 vs 4,6 months; p= 0,06). Prevalence of comorbidities was significantly higher in group 1 both at diagnosis (43,4 vs 11,5%; p <0,005) and at last follow‐up (39,1 vs 11,6%; p <0,02). Use of immunosuppressors, steroids and biologic drugs was similar at diagnosis and at last follow‐up. More IBD patients in group 1 developed side effects related to immunosuppressors (26 vs 4%; p < 0,02), while no difference was observed in biologics‐related side effects. The need for surgery was comparable in the 2 groups (13 vs 13,9 %), whereas mortality was slightly higher in patients with IBD and genetic syndrome (13 vs 7%).

Conclusions: In pediatric IBD patients, the presence of GSs does not significantly modify the course of the disease itself but increases diagnostic and therapeutic complexity.

Contact e‐mail address: disariofrancesca@gmail.com

HIGH FAECAL PH, LOW MICROBIAL LOAD ASSOCIATE WITH FAECAL CALPROTECTIN NORMALISATION IN CHILDREN WITH CROHN'S DISEASE FOLLOWING EXCLUSIVE ENTERAL NUTRITION IN A MULTICENTRE, PROSPECTIVE STUDY

Konstantinos Gkikas¹, Maria Lima¹, Caroline Kerbiriou¹, Shona Mckirdy¹, Ben Nichols¹, Lisa Gervais², Gillian Smith³, Lawrence Armstrong⁴, Thomas Jordan³, Iain Chalmers^5,6, Hannah Barlow⁷, Ghassan Hourani⁸, Rafeeq Muhammed⁹, David Wands², Priya Narula¹⁰, Minal Patel¹¹, Umer Ijaz¹², Simon Milling¹³, Marco Gasparetto¹⁴, Paul Henderson¹⁵, Anna Wilson¹⁵, Richard Hansen², Richard Russell¹⁵, Konstantinos Gerasimidis¹

¹School Of Medicine, Dentistry And Nursing, University of Glasgow, Glasgow, United Kingdom, ²Paediatric Gastroenterology, Hepatology And Nutrition, Royal Hospital for Children, Glasgow, United Kingdom, ³Paediatrics, University Hospital Wishaw, Wishaw, United Kingdom, ⁴Paediatrics, University Crosshouse Hospital, Crosshouse, United Kingdom, ⁵Paediatric Gastroenterology, Aberdeen Children's Hospital, Aberdeen, United Kingdom, ⁶Paediatric Gastroenterology, Tayside Children's Hospital, Dundee, United Kingdom, ⁷Paediatrics, Royal Manchester Children's Hospital, Manchester, United Kingdom, ⁸Paediatrics, Forth Valley Royal Hospital, Larbert, United Kingdom, ⁹Paediatric Gastroenterology, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom, ¹⁰Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, United Kingdom, ¹¹Paediatric Gastroenterology, Royal London Children's Hospital, London, United Kingdom, ¹²James Watt School Of Engineering, University of Glasgow, Glasgow, United Kingdom, ¹³School Of Infection And Immunity, University of Glasgow, Glasgow, United Kingdom, ¹⁴Paediatric Gastroenterology, Norfolk and Norwich University Hospitals, Norwich, United Kingdom, ¹⁵Paediatric Gastroenterology, Hepatology And Nutrition, Royal Hospital for Children and Young People, Edinburgh, United Kingdom

Objectives and Study: Normalisation of faecal calprotectin (FCAL) following therapy with exclusive enteral nutrition (EEN) varies among patients with Crohn's disease (CD), even in those who enter clinical remission. To understand disease characteristics related to EEN efficacy and its mechanism of action, we compared clinical and microbial parameters according to normalisation of FCAL at EEN completion.

Methods: Children with CD (6‐17 years), clinically responding to EEN, were recruited from 11 UK hospitals (January 2020‐ May 2023, NCT04225689) and provided a single faecal sample before EEN completion. Patients were divided into groups according to FCAL levels at EEN completion (FCAL<250 and FCAL>250 mg/kg). Faecal short chain fatty acids (SCFA), faecal sample characteristics (pH, water content (%), bristol stool score), total microbial load (qPCR) and anthropometric and clinical parameters (blood inflammatory markers, use of immunosuppressants, disease duration, disease location) were compared between the two groups. Machine learning using feature elimination was performed to identify associations between clinical, anthropometry, microbial parameters and FCAL normalisation.

Results: Of 84 recruited children, 35 (42%) had an FCAL below 250 mg/kg. Patients with FCAL<250mg/kg had a higher faecal pH and lower microbial load [faecal pH; FCAL<250 mg/kg: 8.3 (8.1, 8.6) vs FCAL>250 mg/kg; 7.95 (7.6, 8.3), p=0.001; microbial load (log10 16S rRNA gene copies/g): FCAL<250mg/kg: 10.7 (10.4, 10.9) vs FCAL>250mg/kg: 11.0 (10.5, 11.2), p=0.02]. Median BMI z‐scores were non‐significantly (p=0.052) higher in patients with FCAL<250mg/kg. A multicomponent random forest model (clinical, blood inflammatory markers, anthropometry, faecal parameters) predicted normalisation of FCAL with 71% accuracy (sensitivity: 69%, specificity: 71%, p<0.001, Figure 1). Higher faecal pH, BMI z‐scores and lower total microbial load were the most influential parameters relating to FCAL<250mg/kg.

Conclusions: The efficacy of EEN in reducing gut inflammation might be, at least in part, mediated via reducing gut bacterial biomass and modulating luminal pH and their downstream effects on inflammatory microbial parameters.

Contact e‐mail address: konstantinos.gkikas@glasgow.ac.uk

REAL WORLD DATA ON ANTI‐TUMOUR NECROSIS FACTOR MAINTENANCE THERAPY IN PAEDIATRIC CROHN'S DISEASE AND APPLICABILITY OF A DE‐ESCALATION STRATEGY FOR PATIENTS IN SUSTAINED CLINICAL REMISSION

Renz Klomberg¹, Anouk Camman¹, Julie Mooij¹, Joep Neven¹, Frank Ruemmele², Nicholas Croft³, Lissy De Ridder¹

¹Paediatric Gastroenterology, Erasmus MC ‐ Sophia Children's Hospital, Rotterdam, Netherlands, ²Pediatric Gastroenterology And Nutrition Unit, Necker Enfants Malades Hospital, Paris, France, ³Paediatric Gastroenterology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom

Objectives and Study: De‐escalation of standard‐regimen anti‐tumour necrosis factor [anti‐TNF] therapy in children with Crohn's disease [CD] with sustained clinical remission [SCR] is infrequent due to the uncertain risk of relapse. This study investigates patterns of initiation and withdrawal of anti‐TNF therapy and aims to identify patients in SCR with anti‐TNF maintenance who might benefit from de‐escalation.

Methods: Children <18 years with newly‐diagnosed CD were enrolled (January 2017 – September 2023) in the prospective multicentre PIBD‐SETQuality inception cohort. Analysis included patients initiating anti‐TNF with ≥1 year of follow‐up. Data collected half‐yearly included disease characteristics, CRP, faecal calprotectin [FCP], MINI‐index, and anti‐TNF details, including therapeutic drug monitoring [TDM] when available. SCR was defined as a wPCDAI <12.5 without flare or with quiescent disease (physician assessed) in the prior 6 months.

Results: Anti‐TNF was initiated in 224/306 (73%) children with CD, and 200 (89%) remained on anti‐TNF maintenance after one year. Only 4/224 discontinued anti‐TNF within the first year while in SCR. Among those on one‐year anti‐TNF maintenance therapy, 87/155 with known SCR status (56%) were in SCR. Patients in SCR exhibited more often low FCP levels (<250 mcg/g; 77% vs. 44%, p=0.02). Anti‐TNF timing, dosing, interval, and TDM results did not significantly differ between SCR and non‐SCR groups. Of 53 patients in SCR at one year with additional follow‐up, only one subsequently ceased anti‐TNF, and 46 (87%) remained in SCR on anti‐TNF maintenance up to the last follow‐up (median 728 days [IQR 590‐1106 days]). Patients who remained in SCR were more likely to have a MINI‐index <3 at 1 year (92% vs. 75%; p=0.040).

Conclusions: Most paediatric Crohn's disease patients treated with anti‐TNF, who achieve SCR with 1‐year maintenance treatment, are likely to remain in SCR. A low MINI index at 1 year may identify potential candidates for de‐escalation of standard‐regimen anti‐TNF treatment in patients in SCR.

Contact e‐mail address: r.klomberg@erasmusmc.nl

RISK OF RELAPSE AFTER ANTI‐TNF WITHDRAWAL IN PAEDIATRIC‐ONSET INFLAMMATORY BOWEL DISEASES: A POPULATION BASED‐STUDY

Delphine Ley¹, Ariane Leroyer², Karima Bouhout¹, Claire Dupont³, Dominique Turck¹, Valérie Bertrand⁴, Nathalie Guillon², Pauline Wils⁵, Nicolas Richard⁶, Corinne Gower‐Rousseau⁷, Guillaume Savoye⁶, Hélène Sarter², Mathurin Fumery⁸

¹Division Of Gastroenterology, Hepatology, And Nutrition, Department Of Pediatrics, Univ. Lille, Inserm, CHU Lille, U1286 ‐ INFINITE ‐ Institute for Translational Research in Inflammation, Lille, France, ²Public Health, Epidemiology And Economic Health Unit, Univ. Lille, Inserm, CHU Lille, U1286 ‐ INFINITE ‐ Institute for Translational Research in Inflammation, Lille, France, ³Department Of Pediatrics, Caen University Hospital, Caen, France, ⁴Department Of Pediatrics, Le Havre Hospital, Le Havre, France, ⁵Gastroenterology Unit, Univ. Lille, Inserm, CHU Lille, U1286 ‐ INFINITE ‐ Institute for Translational Research in Inflammation, Lille, France, ⁶Gastroenterology Unit, Rouen University Hospital, UMR 1073 University of Rouen Normandy, Rouen, France, ⁷Research Unit And Public Health, Reims University Hospital, Reims, France, ⁸Gastroenterology Unit, Amiens University Hospital, and Peritox, UMRI01, Université de Picardie Jules Verne, Amiens, France

Objectives and Study: Few data is available on the long‐term risk of relapse after anti‐TNF withdrawal in paediatric‐onset IBD, especially at the population level.

Methods: All paediatric‐onset (<17 years) IBD diagnosed between 1988 and 2011, included in a prospective population‐based study, were retrospectively followed until 2013. Among patients treated with anti‐TNF, the cumulative probability of relapse after anti‐TNF withdrawal was evaluated using a composite outcome (intestinal resection, and/or flare‐related hospitalization, and/or IBD treatment initiation, and/or active disease). Factors associated with relapse were investigated with a Cox model.

Results: Among 1,344 patients, 562 were treated with anti‐TNF. Anti‐TNF was stopped in 73 patients (Crohn's disease (CD): n=66; Ulcerative colitis (UC): n=7) during remission defined by Harvey‐Bradshaw score <4 in CD and Mayo score ≤2 in UC. Among them, median time to anti‐TNF initiation was 1.6 years (IQR, 0.7‐4.0) and median duration of treatment was 1.0 year (0.3‐1.7). The first line anti‐TNF therapy was infliximab in 68 (93%) patients. At anti‐TNF withdrawal, 47 (64%) patients received immunosuppressant. The cumulative probability of relapse after anti‐TNF withdrawal at 1, 3 and 5 years was respectively 62%, 85% and 93%. Median delay of relapse was 9.5 months (7.5‐12.0). The cumulative probability of flare‐related hospitalization at 1, 3 and 5 years was respectively 7%, 7% and 8%. No patient required intestinal resection after median follow‐up of 8.7 (5.8‐13.8) years. In multivariate analysis, median time to anti‐TNF initiation >1 year was the only factor associated with the risk of relapse (HR 0.58, CI95% [0.35‐0.97], p=0.036). Among relapsers, 46 (63%) were retreated with anti‐TNF. Retreatment was effective in 45 (98%) patients after median delay of 3.9 months (3.5‐10.0). Infusion reaction occurred in 2 patients.

Conclusions: In a population‐based cohort of paediatric‐onset IBD, the risk of relapse after anti‐TNF withdrawal was high, but was not associated with major complication. Retreatment with anti‐TNF was effective and well tolerated.

Contact e‐mail address: delphine.ley@chu‐lille.fr

FLEXIBLE SIGMOIDOSCOPY IS AN ALTERNATIVE TO COLONOSCOPY FOR ENDOSCOPIC REASSESSMENT OF CHILDREN WITH ULCERATIVE COLITIS

Rafeeq Muhammed, Akshatha Mallikarjuna

Paediatric Gastroenterology, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom

Objectives and Study: Introduction: Flexible sigmoidoscopy can be done without the need of bowel preparation or laxatives, hence reducing school and work absenteeism for children and parents. Aim: Analysis of reassessment colonoscopy findings of patients with UC who had colonoscopy for endoscopic activity monitoring

Methods: We reviewed the results for patients with ulcerative colitis who had colonoscopy reassessment from October 2021 to October 2022.

Results: Colonoscopies of 64 patients, 29 male (45%) and female 35 (55%) age 5‐18 years (median 5.5 years) were reviewed. Diagnostic colonoscopy of these patients showed ulcerative colitis extent E4 in 45 (70%), E3 in 5 (8%), E2 in 8 (12%) and E1 in 6 (10%) patients. Extent of colonoscopy was up to terminal ileum in 51 (79%), caecum 11 (17%), hepatic flexure 1 (2%) and splenic flexure 1 (2%) patients. Mayo 0 changes were seen in the rectum of 50% of colonoscopies (n=32), 61% in sigmoid colon (n=39), and 70 % in the right colon (n= 45). Out of 32 patients that scored Mayo 0 in the rectum, only 3 patients (9%) had abnormal (Mayo=1) findings in the right colon. 2 of these patients were known to have atypical UC with rectal sparing. Of the 30 patients who had complete endoscopic healing (Mayo score 0) of the rectum and sigmoid colon, only 2 patients (6%) had abnormal findings (Mayo score 1) in the right colon. One of these patients was known to have atypical UC with rectal sparing at diagnosis.

Conclusions: 3 % of the patients with typical ulcerative colitis at the diagnostic colonoscopy showed endoscopic activity in the right colon when complete endoscopic healing was attained either in the rectum or rectum and sigmoid colon. Flexible sigmoidoscopy is a suitable alternative to colonoscopy for the assessment of endoscopic healing in children with typical ulcerative colitis distribution at their diagnostic colonoscopy

Contact e‐mail address: rafeeq.muhammed@nhs.net

CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS ASSOCIATED WITH PAEDIATRIC INFLAMMATORY BOWEL DISEASE: A MULTI‐CENTER RETROSPECTIVE STUDY FROM THE PAEDIATRIC IBD PORTO GROUP OF ESPGHAN

Manar Matar¹, Dita Cebecauerova², Kaija‐Leena Kolho³, Luca Scarallo⁴, Seamus Hussey⁵, Anat Yerushalmy‐Feler⁶, Gemma Pujol‐Muncunill⁷, Helena Jonsson Rolandsdotter⁸, Manuela Distante⁹, Maya Granot¹⁰, Christine Olbjørn¹¹, Cecilia K. Zetterström¹², Marta Velasco Rodríguez‐Belvís¹³, Jan De Laffolie¹⁴, Oren Ledder¹⁵, Stephanie Van Biervliet¹⁶, Victor Navas‐López¹⁷, Johan Van Limbergen¹⁸, Anastasia Karagkiozi¹⁹, Ivana Čopová²⁰, Raanan Shamir¹, Dror Shouval¹

¹Institute Of Gastroenterology, Nutrition And Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel, ²Department Of Paediatric And Adult Rheumatology, Motol University Hospital Motol, Motol, Czech Republic, ³Department Of Pediatric Gastroenteroloy, Children's Hospital, University of Helsinki and HUS, Helsinki, Finland, ⁴Gastroenterology And Nutrition Unit, Meyer children's Hospital, Florence, Italy, ⁵Royal College Of Surgeons Of Ireland And University College Dublin, National Children's Research Centre, Dublin, Ireland, ⁶Pediatric Gastroenterology Institute, Dana‐Dwek Children's Hospital, Tel Aviv University, Tel Aviv, Israel, ⁷Paediatric Gastroenterology, Hepatology And Nutrition Department, Hospital Sant Joan de Déu, Barcelona, Spain, ⁸Department Of Clinical Science And Education, Södersjukhuset, Karolinska Institutet, Sweden And Department Of Gastroenterology, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, ⁹Pediatric Gastroenterology And Liver Unit, Umberto I Hospital, Sapienza University of Rome, Rome, Italy, ¹⁰Pediatric Gastroenterology And Nutrition Unit, Edmond and Lily Safra Children's Hospital,, Tel‐Hashomer, Israel, ¹¹Department Of Pediatric And Adolescent Medicine, Akershus University Hospital, Nordbyhagen, Norway, ¹²Pediatric Gastroenterology, Hepatology And Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden, ¹³Gastroenterology And Nutrition Department, Hospital infantil Universitario Niño Jesús, Madrid, Spain, ¹⁴Department Of General Pediatrics And Neonatology, University Children's Hospital Giessen, University of Giessen, Giessen, Germany, ¹⁵Juliet Keiden Institute Of Paediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ¹⁶Pediateic Gastroenterology, Ghent University hospital, Ghent, Belgium, ¹⁷Pediatric Gastroenterology, Hepatology And Nutrition Unit, Hospital Regional Universitario de Malaga, Malaga, Spain, ¹⁸Department Of Pediatric Gastroenterology And Nutrition, Emma Children's Hospital, Amsterdam, Netherlands, ¹⁹Paidon Aglaia Hyriakou Children's Hospital, Athene, Greece, ²⁰Department Of Pediatric Gastroenterology, Hepatology And Nutrition, University Hospital Motol and 2nd Faculty of Medicine, Motol, Czech Republic

Objectives and Study: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare autoinflammatory bone disorder that has been linked to inflammatory bowel disease (IBD). Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD

Methods: Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in twenty centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, laboratory studies, bone imaging findings and outcomes of each disease.

Results: 45 patients were included (21 [47%] females, median age 10.2 [IQR 12‐13.5] years). Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 2 (13%) exhibiting moderate‐severe IBD activity. In 20 children (44%) IBD preceded CRMO, and at the time of CRMO diagnosis 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate‐severe disease activity; however, CRP and ESR were elevated (1.5 [0.4‐3.4] mg/dL and 35 [21‐55] mm/h, respectively) while median fecal calprotectin was 567 (68‐1800) mcg/gr. In 10 patients (22%) CRMO preceded the diagnosis of IBD (median 46 [25‐248] weeks). Anti‐TNFa were used once CRMO was identified in 33 (94%) patients. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission was achieved in all patients with 22.2 (15‐51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and deformity.

Conclusions: In the largest cohort of IBD and CRMO, to date, CRMO presentation was not related to clinically active intestinal inflammation. CRMO remission was achieved in all patient, but small number of patients developed significant bone complications.

Contact e‐mail address:

INORGANIC POLYPHOSPHATES IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Alexander Meyer, Theresa Margarete Bauer, Harald Haidl, Benno Kohlmaier, Axel Schlagenhauf

Department Of General Paediatrics, Medical University of Graz, Graz, Austria

Objectives and Study: Patients with inflammatory bowel disease (IBD) have a threefold higher risk of developing venous thromboembolism than healthy individuals. Circulating inorganic polyphosphates (PolyP), originating from both platelets and microbes, activate the coagulation system and drive inflammation in experimental studies, but the pathophysiological role of these mechanisms in IBD remains elusive. Conversely, perorally administered PolyP was found to induce mucosal healing in ulcerative colitis‐patients, but may traverse the impaired intestinal barrier in acute‐stage IBD and exacerbate systemic symptoms. Aim of this study was to assess the activity of endogenous PolyP in pediatric IBD‐patients during the acute phase and in clinical remission in comparison to patients with bacterial gastroenteritis (BGE) and healthy individuals.

Methods: We compared 21 pediatric IBD‐patients at initial manifestation, with six pediatric BGE‐patients and 23 healthy controls. IBD‐patients were retested after treatment onset (3‐6 weeks after initial manifestation) and in remission (PCDAI/PUCAI < 10). PolyP activity was assessed in sampled plasma using a newly developed assay that employed calibrated automated thrombography, leveraging PolyP's distinctive capacity to antagonize exogenous tissue factor pathway inhibitor. The outcomes were quantified and expressed as Δlag‐time.

Results: There was a significant difference in absolute lag‐time and the endogenous thrombin potential between controls and IBD‐patients (p = <.001 respectively). Between initial manifestation and remission there was a significant difference in lag‐time (p = .002). PCDAI correlated significantly with lag‐time (r = .67, p = .012). However, no significant difference in Δlag‐time was observed among patient groups or longitudinally in IBD‐patients.

Conclusions: Our study is the first to assess PolyP activity in plasma of IBD‐patients. While a prothrombotic shift was clearly observable in pediatric patients with acute‐phase IBD, endogenous PolyP does not seem to play a contributory role in its etiology. Nevertheless, further investigation is required to explore the iatrogenic effects of perorally administered PolyP.

Contact e‐mail address: a.meyer@stud.medunigraz.at

SINGLE MOLECULAR MECHANISM OF PATHOGENIC VARIANTS OF BIR2 DOMAIN IN XIAP‐DEFICIENT IBD

Juhwan Lee¹, Inki Kim², Seak Hee Oh³, Kyung Mo Kim³, Iksoo Chang⁴

¹iProtein Therapeutics, Daegu, Korea, Republic of, ²Department Of Convergence Medicine, Asan Institutes for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of, ³Seoul Asan Medical Center Children's Hospital, Seoul, Korea, Republic of, ⁴Supercomputing Big Data Center and Core Protein Resources Center, Daegu, Korea, Republic of

Objectives and Study: X‐linked inhibitor of apoptosis protein (XIAP) deficiency (OMIM #300635), caused by mutations in the XIAP gene at Xq25, is associated with a macrophage activation‐like syndrome known as hemophagocytic lymphohistiocytosis and refractory Crohn's disease, for which hematopoietic stem cell transplantation is the only therapeutic option. The XIAP protein plays a critical role in the pro‐inflammatory response via the NOD signaling pathways. In this process, the BIR2 domain of the XIAP protein recruits and ubiquitinates the RIP2 protein by acting as a potent E3 ubiquitin‐protein ligase. There have been some efforts to manipulate mutant XIAP signaling to restore NOD2 signaling. However, the detailed mechanism of XIAP BIR2 mutant proteins has not yet been revealed. In this study, we utilized a digital approach to comprehensively acquire atom‐level structural and thermodynamic insight into mutant BIR2 and then conducted in vitro experimental validation.

Methods: We selected representative XIAP BIR2 mutant proteins that exhibited missense pathogenic variants. Our digital approach for predicting distinct biochemical properties included supercomputing molecular dynamics simulations and multiplex computational assessments for variants. Predictions were subsequently tested through in vitro experimental validations, including conventional immunoprecipitation and fluorescence cross‐correlation spectroscopy on the 293T cell lines.

Results: Co‐immunoprecipitation and fluorescence cross‐correlation spectroscopy showed that wild‐type XIAP and RIP2 preferentially interacted in live cells, whereas all non‐synonymous PV XIAPs failed to interact properly with RIP2. Structural analysis showed that various structural changes by mutations, such as hydrophobic core collapse, Zn‐finger loss, and spatial rearrangement, destabilized the two loop structures (174–182 and 205–215) that critically interact with RIP2. Subsequently, it caused a failure of RIP2 ubiquitination and loss of protein deficiency by the auto‐ubiquitination of all XIAP mutants.

Conclusions: These findings could enhance our understanding of the role of XIAP mutations in XIAP‐deficient inflammatory bowel disease and may benefit new‐drug‐development strategies

Contact e‐mail address: seakhee.oh@amc.seoul.kr

RISK OF FRACTURES IN CHILDREN AND ADULTS WITH INFLAMMATORY BOWEL DISEASE: A REPORT FROM THE EPI‐IIRN

Esther Orlanski‐Meyer¹, Rachel Buchok², Amir Ben Tov³, Natan Ledderman⁴, Yiska Loewenberg Weisband⁵, Eran Matz⁶, Iris Dotan^7,8, Dan Turner^1,9, Amit Assa¹

¹The Juliet Keidan Institute Of Pediatric Gastroenterology, Hepatology, And Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel, ²Juliet Keidan Institute Of Pediatric Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel, ³Maccabi Health Services, Tel Aviv, Israel, ⁴Meuhedet Health Services, Tel Aviv, Israel, ⁵Clalit Health Services, Chief's Office,Clalit Research Institute, Tel Aviv, Israel, ⁶Leumit Health Services, Tel‐ Aviv, Israel, ⁷Division Of Gastroenterology, Rabin Medical Center, Rabin Medical Center, Petah Tikva, Israel, ⁸Faculty of Medicine, Tel Aviv University, Tel‐Aviv, Israel, ⁹Pediatric Gastroenterology, Shaare Zedek Medical Center, Great Ormand St Hospital, Jerusalem, Israel

Objectives and Study: Patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, but the risk for bone fractures is debated. We aimed to assess this risk using the epi‐Israeli IBD Research Nucleus (IIRN) data.

Methods: Data of patients with IBD and non‐IBD matched controls (approximately 3 non‐IBD controls/case) were retrieved from the epi‐IIRN cohort (January 2005‐ June 2020) including all IBD patients from the four Israeli HMOs. Data included demographics, osteoporosis medications, fractures and IBD characteristics. Patients were stratified by age (0‐17,18‐49, and >50).

Results: We included 32,263 patients with IBD and 89,423 non‐IBD controls [48% female, 56% Crohn's disease (CD)]. Time to first fracture was significantly shorter for all age groups except for pediatric males (Figure). Rates of fractures, osteopenia and osteoporosis were higher in patients with IBD versus controls for all age groups. Subgroup analysis showed that fracture rate did not differ between CD and ulcerative colitis (UC), but osteopenia/osteoporosis were higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88‐1.16) for males and 1.17(0.95‐1.44) for females, in adults 1.08 (0.99‐1.16) for males and 1.12 (1.02‐1.21) for females, in the elderly 1.2 (1.08‐1.32) for males and 1.19 (1.08‐1.31) for females. Arthritis was associated with fracture risk [HR: children 1.47 (1.15‐1.88); adults 1.3 (1.17‐1.44); elderly 1.19 (1.07‐1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long‐term proton pump inhibitors usage were associated with an increase in fracture risk.

Conclusions: In this large nationwide cohort, patients with IBD had higher risk for bone fractures than matched controls in almost all ages, with no difference between CD and UC. The rate of osteopenia/osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at‐risk population.

Contact e‐mail address:

EVALUATION OF FECAL NGAL LEVELS IN CHILDHOOD INFLAMMATORY BOWEL DISEASES

Aysenur Kardas Yildiz, Nafiye Urgancı, Merve Kesim Usta

Department Of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

Objectives and Study: Inflammatory bowel disease (IBD) is a chronic and progressive disease. Calprotectin, which is used in the diagnosis and follow‐up of the disease, is released from neutrophilic granulocytes in inflammation. Neutrophil Gelatinase Associated Lipocalin (NGAL) is strongly expressed in the intestinal epithelial cell layer in addition to expression in granulocytes. In our study, we aimed to compare fecal NGAL (FNGAL) with fecal calprotectin (FCAL), thinking that FNGAL could be a valuable biomarker in the diagnosis and follow‐up of IBD.

Methods: Our study was designed as prospective and single‐center. 66 children, IBD (n=44) group and the healthy control group (n=22), were included in the study. The IBD group was divided into two groups as activation (n=23) and remission (n=21). Clinical diagnoses, activity scores, serum and stool markers of the patients were recorded. FNGAL level was studied by ELISA method. SPSS 15.0 program was used for statistical analysis.

Results: In our study, there was no significant difference in the mean age and gender ratios of the patient and control groups. FNGAL levels of the patient group were significantly higher than the control group (p=0.007). When ROC analysis was performed, FNGAL was found to be 95.5% sensitive and 81.8% specific in determining the activation of the disease, while FCAL was found to be 86.7% sensitive and 85.7% specific. Comparison of FNGAL Levels of Patient and Control Group.

Conclusions: In our study, the fact that FNGAL level was higher in the patient group than in the control group shows that it can be used in diagnosis. In addition, it is more sensitive than FCAL in determining activation, indicating that it may be a valuable marker in the monitoring of the disease.

Contact e‐mail address:

CROHN'S DISEASE EXCLUSION DIET VERSUS EXCLUSIVE ENTERAL NUTRITION IN PEDIATRIC PATIENTS WITH CROHN'S DISEASE

Lourdes Mora Massó, Ana Martín Adrados, Amalio Fernández Leal, Marta Velasco Rodríguez‐Belvís, Laura Palomino Pérez, Marianna Alejandra Di Campli Zaghlul, Carmen Martín Fernández, Aruca Raquel Chapinal Andrés, Evangelina Muñoz Bravo, Agustín De La Mano Hernández, Elvira Cañedo Villarroya, Jorge Martínez Pérez, Gloria Domínguez‐Ortega, Nuria Puente Ubierna, Paula Sánchez Llorente, Sara Moreno Pérez, Almudena Muñoz González, Rosa Ana Muñoz Codoceo

Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Objectives and Study: Crohn's disease exclusion diet (CDED) has emerged as an alternative to exclusive enteral nutrition (EEN) to induce remission in pediatric CD patients. CDED is better tolerated, and can represent a long‐term strategy, as opposed to EEN. The aim is to compare the outcomes of both diets in our clinical setting.

Methods: Retrospective and observational study on CD patients under follow‐up in a pediatric Inflammatory bowel disease (IBD) Comprehensive Care Unit from a tertiary hospital (June to October 2023). We included pediatric CD patients (under 18) who received one of these two diets as induction treatment both as monotherapy and in combination with other drugs. Anthropometric values, inflammatory markers and clinical activity indexes were compared in both groups in three different time points: prior to induction (time 0), and three (time 1) and six months (time 2) after the induction. This study was approved by the Ethics Committee of HIUNJ. Data were analyzed with the SPSS software (v.25).

Results: A total of 53 patients were included: 24 in the CDED group and 29 in the EEN group. Up to 48 patients (90,6%) simultaneously started another drug as part of the maintenance strategy. The decrease of faecal calprotectin (FC) was more striking in the CDED group but kept elevated in both, whereas C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) descended to normal values after both diets. However, there were no statistically significant differences regarding anthropometric values, inflammatory markers, or clinical activity indexes between the two groups at each time point (see figure).

Conclusions: Although the concomitant use of other drugs limits the drawing of conclusions, the therapeutic use of both diets seems useful to achieve clinical, analytical, and anthropometric improvement in pediatric CD patients. Conducting more studies on larger samples would help to confirm the role of CDED as an effective alternative to EEN.

Contact e‐mail address: martavrb@gmail.com

RENAL FAILURE IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

Stephanie Vuijk¹, Renz Klomberg¹, Astrid Hellendoorn¹, Polychronis Kemos², Martine Aardoom¹, Frank Ruemmele³, Femke Vrieling‐Prince⁴, Nicholas Croft², Lissy De Ridder¹, Pibd Setquality Consortium¹

¹Paediatric Gastroenterology, Erasmus Medical Centre ‐ Sophia Children's Hospital, Rotterdam, Netherlands, ²Paediatric Gastroenterology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom, ³Pediatric Gastroenterology And Nutrition Unit, Université Paris Cité, Faculté de Santé, UFR de Médecine, APHP, Hôpital Universitaire Necker Enfants Malades, Paris, France, ⁴Paediatric Nephrology, Erasmus Medical Centre ‐ Sophia Children's Hospital, Rotterdam, Netherlands

Objectives and Study: Renal manifestations may occur in children with inflammatory bowel disease (IBD) and can lead to acute renal failure, a severe complication and associated with a risk of developing chronic kidney disease (CKD). This study aimed to investigate cases of renal failure in children with IBD.

Methods: Cases of renal failure in children <19 years with IBD were collected from the international, prospective PIBDSETQuality Safety Registry¹. A monthly survey was sent to participating paediatric gastroenterologists throughout the world to report cases of renal failure (defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m²⁾. Upon reporting a case of renal failure, a follow‐up form was automatically sent to obtain information about renal failure, IBD characteristics and outcomes (including CKD, defined as eGFR <60 for >3 months).

Results: From November 2016 until August 2023, 220 gastroenterologists from 36 countries participated in the Safety Registry and 38 cases of renal failure were included. Median age at renal failure was 15 years (IQR 13‐17), median time from diagnosis until renal failure was 28 months (IQR 6.5‐66.5) and 66% of patients were diagnosed with Crohn's Disease (CD). The most likely reported diagnoses of renal failure are represented in Figure 1. Twelve cases were confirmed with renal biopsy. The most frequently reported diagnosis was tubulo‐interstitial nephritis. In 68% of the patients, creatinine was measured during routine follow‐up, not due to kidney‐related symptoms. Nine patients developed CKD, two patients required renal replacement therapy.

Conclusions: This is the first prospective study to report cases of renal failure in children with IBD. Renal failure can occur without symptoms, and may lead to CKD. Timely identification of renal failure is important to adequately treat and monitor patients. We recommend to monitor creatinine in children with IBD every 6 months. References: 1.Aardoom et al.BMJOpen.2020

Contact e‐mail address: s.a.vuijk@erasmusmc.nl

PERIPHERAL BLOOD EOSINOPHILIA AT DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE IS ASSOCIATED WITH SEVERE DISEASE COURSE; A NATIONWIDE STUDY FROM THE EPI‐IIRN COHORT

Anat Yerushalmy‐Feler¹, Rona Lujan², Yiska Loewenberg Weisband³, Shira Greenfeld⁴, Amir Ben Tov⁵, Natan Ledderman⁶, Eran Matz⁷, Iris Dotan⁸, Raffi Lev‐Tzion⁹, Idan Goren¹⁰, Dan Turner⁹, Shlomi Cohen¹

¹Pediatric Gastroenterology Institute, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ²Juliet Keidan Institute Of Pediatric Gastroenterology Hepatology And Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel, ³Clalit Health Services, Clalit Research Institute, Tel Aviv, Israel, ⁴Maccabi Health Services, Tel Aviv, Israel, ⁵Kahn‐Sagol‐Maccabi Research and Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel, ⁶Meuhedet Health Services, Tel Aviv, Israel, ⁷Leumit Health Services, Tel‐ Aviv, Israel, ⁸Division Of Gastroenterology, Rabin Medical Center, Rabin Medical Center, Petah Tikva, Israel, ⁹Juliet Keidan Institute Of Pediatric Gastroenterology Hepatology And Nutrition, Shaare Zedek Medical Center; Hebrew University of Jerusalem, Jerusalem, Israel, ¹⁰Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, United States of America

Objectives and Study: We conducted this nationwide study to evaluate the association between peripheral blood eosinophilia (PBE) and long‐term outcomes in children and adults with inflammatory bowel diseases (IBD).

Methods: Data from the epi‐IIRN cohort included patients with IBD diagnosed between 2005‐2020 who had a validated eosinophil count at diagnosis, and those of non‐IBD controls. Time‐to‐outcome was determined by Cox proportional adjusted models. Severe disease course was defined as corticosteroid dependency, use of ≥2 biologics from different classes, or surgery.

Results: Included were 28,133 patients (15,943 Crohn's disease [CD] and 12,190 ulcerative colitis [UC]), and 28,724 non‐IBD controls. The prevalence of PBE was 13% in the IBD group and 5% in controls (P < .001). PBE was more prevalent in UC (16.1%) compared to CD (10.6%, OR=1.52 (95%CI 1.42‐1.63); P < .001) and in pediatric‐onset (23.5%) compared to adult‐onset (11%) IBD (OR=2.14 (1.97‐2.31); P <.001). In a multivariate Cox model, PBE was an independent predictor of severe IBD in CD (hazard ratio [HR]=1.14, 95%CI 1.04‐1.24, P < .001) and UC (HR=1.37, 95%CI 1.28‐1.47 P < .001). PBE also predicted time‐to‐hospitalization (HR=1.24, 95%CI 1.19‐1.30), use of corticosteroids (HR=1.32, 95%CI 1.28‐1.36), corticosteroid dependency (HR=1.37, 95%CI 1.31‐1.43), need of biologics (HR=1.27, 95%CI 1.21‐1.33), and of a second biologic (HR=1.36, 95%CI 1.23‐1.49, all P < .001).

Conclusions: In this largest nationwide study, PBE at diagnosis was a predictor of severe IBD course. These findings support the use of PBE as a marker of adverse long‐term outcome and as a potential target for future therapies.

Contact e‐mail address: ANATY11@YAHOO.COM

F. PRAUSNITZII‐DERIVED EXTRACELLULAR VESICLES ATTENUATE EXPERIMENTAL COLITIS BY INHIBITING INTESTINAL INFLAMMATION AND ENHANCING MUCOSAL BARRIER FUNCTION IN MICE

Lin Ye, Yizhong Wang, Fangfei Xiao, Xufei Wang, Xiaolu Li, Ting Zhang

Department Of Gastroenterology, Hepatology, And Nutrition, Shanghai Children's Hospital, Shanghai, China

Objectives and Study: Here, we aimed to evaluate the attenuating effect of EVs derived from F. prausnitzii (Fp‐EVs) on dextran sulfate sodium (DSS)‐induced colitis mice, and explored the potential mechanism of Fp‐EVs in inflammatory bowel disease (IBD).

Methods: We isolated and characterized the EVs derived from F. prausnitzii (Fp‐EVs). In vivo, C57BL/6 mice were orally administered Fp‐EVs (200 μg/200 μlL) for 5 days prior to colitis induction by DSS. The disease activity index (DAI) was analyzed, and intestinal epithelial mucosal barriers, immune response and inflammatory cytokines were mearsured. In vitro, RAW246.7 macrophages and Caco‐2 cells were used to investigate the protective roles of Fp‐EVs on lipopolysaccharide (LPS)‐induced inflammatory response and epithelium barrier dysfunction. Furthermore, protein composition and microRNA‐sized small RNAs (msRNAs) were analyzed by high‐throughput sequencing.

Results:Fp‐EVs treatment reduced DSS induced weight loss, DAI score, colon length shortening and histological damage. Fp‐EVs treatment decreased neutrophil infiltration and apoptotic cells in colitis mice. Fp‐EVs upregulated the protein expression of tight junction and anti‐oxidant protein, and increased the ratio of Tregs in the colon tissues of colitis mice. Furthermore, Fp‐EVs downregulated the expression of the proinflammatory cytokines and upregulated the anti‐inflammatory cytokines in colitis mice. Mechanistically, proteomic and msRNA analysis revealed that Fp‐EVs were enriched with proteins involved in inflammatory signaling pathway, such as mitogen activated protein kinase (MAPK) pathway. We further found that Fp‐EVs treatment markedly reduced the phosphorylation of proteins NF‐κB and MAPK. Moreover, the mimics of Fp‐EVs‐derived msRNA 4486, the highest abundance of msRNA in both F. prausnitzii and Fp‐EVs, downregulated the phosphorylation of NF‐κB and MAPK in LPS induced Caco‐2 cells and colon tissue induced by DSS.

Conclusions: Our findings reveal that Fp‐EVs attenuate experimental colitis by modulating intestinal mucosal barrier function and the immunological profile. In addition, Fp‐EVs‐derived msRNA 4486 could alleviated experimental colitis through inhibiting p‐ NF‐κB/MAPK pathway.

Contact e‐mail address: zhangt@shchildren.com.cn

GUT MICROBIOTA ALTERED BY INFLIXIMAB TREATMENT IMPROVES INTESTINAL EPITHELIAL HOMEOSTASIS AND AMELIORATES EXPERIMENTAL COLITIS

Fangfei Xiao, Lin Ye, Xufei Wang, Xiaolu Li, Yizhong Wang, Ting Zhang

Department Of Gastroenterology, Hepatology, And Nutrition, Shanghai Children's Hospital, Shanghai, China

Objectives and Study: To explore the effect of gut microbiota altered by infliximab (IFX) treatment on dextran sulfate sodium (DSS) ‐induced colitis in mice and the possible mechanism.

Methods: C57BL/6 mice were induced acute colitis by 2.5% (w/v) DSS in drinking water and subsequently treated with fecal microbiota or sterile fecal filtrate from IFX‐treated colitis mice or CD patients once daily by gavage for 3 days. The expressions of β‐catenin and Ki‐67 in the colon were detected by immunofluorescence. Then, RNA sequencing was performed on colonic tissues to screen for differential genes. The differential gene expression in the colon was verified by qPCR. Finally, differential gene receptor knockout mice were breed and cultured. The knockout mice were induced acute colitis by 2.5% (w/v) DSS in drinking water and subsequently treated with fecal microbiota from IFX‐treated pediatric CD patients once daily by gavage for 3 days. And changes in weight and DAI score, colon length, histopathological morphology and pathological score were recorded.

Results: Fecal microbiota from IFX‐treated pediatric CD patients, fecal microbiota and supernatant of colitis mice after IFX treatment could promote the recovery of body weight, DAI, colon length, and pathological damage in mice, and inhibit the expression of colonic pro‐inflammatory factors IL‐6 and IL‐1β, promote the proliferation of colonic epithelial cells, thereby promoting the intestinal tract inflammation recovery. RNA sequencing and qPCR results confirmed that Fecal microbiota from IFX‐treated pediatric CD patients induced the expression of type I interferon (IFN) pathway‐related genes (ISG15, STAT2, RIG1, USP18, OAS3, OAS2, and IRF7). In IFNAR1^‐/‐ mice, IFX‐treated altered gut microbiota failed to ameliorate weight loss, colon shortening, and pathological damage in DSS‐induced acute colitis mice.

Conclusions: The gut microbiota in the remission period after IFX treatment depended on the type I IFN pathway to promote the recovery of intestinal inflammation in mice with acute colitis.

Contact e‐mail address: zhangt@shchildren.com.cn

HEALTH LITERACY IMPACT FACTOR IN INCREASE DIAGNOSIS OF CELIAC DISEASE

Henedina Antunes^1,2, Francisco Lima³, Aurélio Mesquita³

¹Life And Health Sciences Research Institute (icvs), Icvs/3b's Associated Laboratory And School Of Medicine, University of Minho, Braga, Portugal, ²Gastroenterology, Hepatology And Nutrition Pediatric Unit And Clinic Academic Center, Hospital de Braga, Braga, Portugal, ³Clinical Pathology Department, Hospital de Braga, Braga, Portugal

Objectives and Study: This study investigates the impact of health literacy on the diagnosis of celiac disease (CD) in Braga Hospital, particularly focusing on the shift in diagnostic patterns among adults post the implementation of awareness initiatives. Before 2018, Braga Hospital had 169 CD patients, with 132 being diagnosis in pediatric age and 37 in adults (21.89%). A campaign in 2018 aimed to raise awareness about CD beyond pediatric age, encouraging General Practitioners (GPs) to utilize tissue transglutaminase (TG2) in diagnosis.

Methods: The study is from 1^st January 2019 to 30^th June 2023 employing anti‐tissue transglutaminase type 2 antibodies (IgA TG2) as part of the diagnostic criteria following ESPGHAN guidelines for DC diagnosis. The TG2 positive is more than 10AU/ml. The TG2 tests positive 10 times (more than 100AU/ml) give opportunity to avoid the need for duodenal biopsies.

Results: The region's population increased by 6.5% between 2010 and 2021. Over the last 4.5 years, 4676 TG2 tests were conducted, with 336 (7.18%) positive. The need for duodenal biopsies varied annually: 31,11% in 2019, 15.79% in 2020, 37,31 in 2021, 57,69% in 2022, and 44,83% in 2023. Pediatric cases showed and increasing trend: 31,11% (2019), 38,60% (2020), 40,00% (2021), 25,96% (2022)*, and 31.03% (first half of 2023). The total comprises 107 pediatric and 229 adult patients. Notably, post‐2018, 68.15% of first‐time CD diagnosis occurred in adults.

Conclusions: This study underscores the vital role of health literacy in CD diagnosis cross all age groups. The significant increase in adult diagnoses post‐2018 suggests the success of awareness initiatives, emphasizing the importance of continued efforts in health education. Acknowledgments to GPs for their role in this positive shift in diagnostic patterns. Continued efforts in health literacy are crucial for the timely identification and management of celiac disease across diverse age demographics. *In 2022:I was outside HBraga.

Contact e‐mail address: henedinaantunes@gmail.com

ASSESSMENT OF THE STATE OF “TIGHT JUNCTIONS” IN PATIENTS WITH GLUTEN‐RELATED DISEASES

Svetlana Geller, Gulnoza Azizova, Noiba Azimova, Kamola Usmanova, Dilrabo Abdullaeva, Zulkhumor Umarnazarova, Altinoy Kamilova

Gastroenterology, Republican Specialized Scientifical Practical Medical Center of Pediatrics, Tashkent, Uzbekistan

Objectives and Study: Gluten alters the properties of intestinal epithelial barrier. In recent years, much attention has been paid to new markers of permeability, such as zonulin. Therefore, the purpose was to evaluate the state of the “tight junctions” of the intestinal barrier in gluten‐related diseases.

Methods: In 2021–2023 years single‐center prospective study was conducted on 130 children aged 1 to 16 years with gluten‐related diseases. The level of fecal zonulin was assessed by using an ELISA kit IMMUNDIAGNOSTIK (Germany). Control group were 30 healthy children.

Results: Children with celiac disease (CD) were 69 (53.1%), wheat allergy (WA) ‐ 39 (30.0%), non‐celiac gluten sensitivity (NCGS) ‐ 22 (16.9%). The mean zonulin level in patients with CD was 182.3+64.3 ng/ml, which was 2 times higher than the control values ‐ 90,3±15,2 ng/ml (p<0.02). A significant increase was present in 54.3% of children (283.4 + 28.1 ng/ml, p<0.001 relative to control). In case of WA, the values of zonulin were 1.5 times lower than in first group (122.3 + 18.1 ng/ml), but in 50.5% it exceeded the norm (average value – 185.9 + 16.8 ng/ml, p<0.002 relative to control). In the group of children with NCGS, zonulin was increased in 72.7%, but not as intensely as in CD ‐ 180.0 + 17.1 ng/ml, p <0.002 relative to the control (group average ‐ 147.6 + 21 .1 ng/ml). In NCGS a moderate negative linear correlation between the levels of zonulin and hemoglobin was found (‐0.53), in CD and WA, it was a weak negative linear correlation ‐0.36 and ‐0.37, respectively. For WA, a moderate positive linear correlation between zonulin and the age of gluten introduction was found (0.65).

Conclusions: Thus, it is necessary to pay attention to the state of the intestinal barrier when conducting a comprehensive assessment and treatment of patients with gluten‐related diseases.

Contact e‐mail address: geller_svetlana@mail.ru

ANALYSIS OF 3 AND 4‐GENERATION COELIAC FAMILIES REVEALS CONTRIBUTION OF TWO MAJOR NON‐HLA GENES

Ilma Korponay‐Szabo^1,2, Judit Gyimesi¹, Emese Récsányi¹, Márta Balogh³, Endre Barta^4,5

¹Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary, ²Dept. Of Paediatrics, University Of Debrecen, Debrecen, Hungary, ³Paediatrics, Vas County Markusovszky Teaching Hospital, Szombathely, Hungary, ⁴Dept. Of Biochemistry And Molecular Biology, University Of Debrecen, Debrecen, Hungary, ⁵Institute Of Genetics And Biotechnology, Hungarian University of Agriculture and Life Sciences, Gödöllő, Hungary

Objectives and Study: Coeliac disease (CeD) has a complex inheritance pattern where HLA‐DQ2/DQ8 alleles are gating the effect of the causative coeliac genes which are not yet identified. In this study we evaluated multiple affected families for the transmission of CeD in at least three generations.

Methods: Altogether 45 family pedigrees were included which contained 70 CeD grandparent – CeD grandchild pairs and 2 CeD grand‐grandparent – CeD grand‐grandchild pairs. Celiacs, parents and sibs of the affected children were genotyped for HLA‐DQ2.5, 2.2, DQ8 and DQ7 by Taqman SNP probes and screened for anti‐transglutaminase (TGA) and endomysial (EMA) antibodies. The diagnosis of CeD was based on histology and seropositivity according to ESPGHAN 1990 and 2020 criteria as appropriate for age.

Results: The female/male ratio was 2.23 among the CeD grandparents, 1.25 in the parents and 1.65 among the CeD grandchildren. CeD grandparents had on average 1.65 affected granddchildren (1‐4) and 2.6 not affected grandchildren. From the 54 subjects who were at the same time parents of a CeD grandchild and offsprings of a CeD grandparent, 29 (54%) were affected and/or TGA/EMA+, but 25 (46%) were not affected. DNA samples were available from 22 of the not affected parents of whom 21 had full DQ2.5 or DQ8 heterodimers and one had DQ2.2. In one of the two 4‐generation families all 4 generations had CeD, whereas in the other only the grand‐grandparent, the parent and the grand‐grandchild were affected and the healthy grandparent did not have either DQ2 or DQ8.

Conclusions: Our results indicate that one major non‐HLA genetic component (No.1) follows a Mendelian transmission and when not present in CeD offspings, they remain healthy despite carrying HLA‐DQ2/DQ8 and transmitting CeD to their own children by one other major celiac gene (No.2). This may happen by the contribution of the other parent carrying a permissive No.1 gene allele.

Contact e‐mail address: ilma.korponay‐szabo@tuni.fi

LYMPHOCYTIC ENTERITIS MARSH 1: IS THE SILENT PRECURSOR OF CELIAC DISEASE?

Saray Mesonero Cavia¹, Elena Robert Gil², Ana Moya Ortega², Albert Martín Cardona³, Tomás Pérez Porcuna², Maria Esteve Comas³, Roger García Puig¹

¹Department Of Pediatric Gastroenterology, Hepatology And Nutrition, Hospital Universitari Mutua Terrasa, Terrassa, Barcelona, Spain, ²Hospital Universitari Mutua Terrasa, Terrassa, Barcelona, Spain, ³Gastroenterology, Hospital Universitari Mutua Terrasa, Terrassa, Spain

Objectives and Study: Marsh1 histological findings in celiac disease(CD) represent diagnostic challenges. Few of Marsh1 cases evolve into celiac disease. Objetive:To analyze the predictive factors for the development of CD.

Methods: Retrospective cohort study of patients with Marsh1(2011‐2018) and clinical suspicion of CD. Progression until 2023 was assessed. Clinical and analytical variables, gluten‐free diet indication and response were collected. Factors associated with CD were analyzed in univariate and multivariate analyses(SPSSv25)

Results: Patient characteristics Table1. Patient follow‐up revealed 32% celiacs, and 67% non‐celiacs. Symptomatic patients had a higher progression rate(35%) than asymptomatics. Seronegatives, 84% did not develop CD, while 60% of seropositive individuals did it(p<0.05). Flow cytometry findings indicated that celiac pattern was associated with more CD progression(67%) than incomplete pattern(46%) or normal pattern(6.7%)(p<0.05). The mean difference in Intraepithelial lymphocytes (ILEs) counts between the two groups is marginally significant(p=0.084). A marginally‐significant correlation is also observed between IELs and TCRγδ+(p=0.052). Seronegative individuals with celiac‐pattern had a higher CD risk (X10.4). Re‐biopsied patients showed: celiac‐pattern remained in 50%, transitioned to incomplete‐pattern 33%, and returned to normal‐pattern 16%. Incomplete pattern was maintained in 80% and progressed to celiac pattern 20%.Normal‐pattern transitioned to incomplete in 17%. 100% of seropositive patients had altered cytometric pattern, 71% celiac pattern and 29% incomplete‐pattern. 50% of seronegative individuals had altered cytometric pattern. Seronegatives with celiac pattern had a higher risk of CD (p=0.009) (OR=10.4 95%) No differences in %TCRγδ+ among sex, age, or clinical presentation.

Conclusions: Flow cytometry analysis of IELs may aid in classifying individuals with Marsh 1, as well as for seronegative patients and risk factors. It discriminates between those more likely to have CD and those less likely. The rise in TCRγδ+ persists regardless of diet. Serology remains a good predictor when other causes ruled out. In cases of uncertainty, it is crucial to combine all available diagnostic tools and maintain a close follow‐up.

Contact e‐mail address: saraymes@gmail.com

INTERNATIONAL TRENDS IN PEDIATRIC COELIAC DISEASE MANAGEMENT: A GLOBAL SHIFT TOWARDS NO‐BIOPSY APPROACH

Petra Rižnik¹, Henedina Antunes², Asaad Assiri³, Renata Auricchio⁴, Nevzat Aykut Bayrak⁵, Amir Ben Tov⁶, Joanna Bierła⁷, Nada Boutrid⁸, Denis Chang^9,10, Maria Luz Cilleruelo¹¹, Paula Crespo‐Escobar^12,13, Andrew Day^14,15, Veselinka Djurišić¹⁶, Natasa Dragutinovic¹⁷, Marisa Gallant Stahl¹⁸, Svetlana Geller¹⁹, Peter Gillett²⁰, Gieneke Gonera²¹, Natalia Gromnatska²², Urszula Grzybowska‐Chlebowczyk²³, Anat Guz Mark²⁴, Judit Gyimesi²⁵, Almuthe Christina Hauer²⁶, Angharad Hurley¹⁴, Fatma Iknur Varol²⁷, Hilary Jericho^28,29, Tina Kamhi³⁰, Martina Klemenak¹, Krasimira Koleva³¹, Michal Kori^32,33, Ilma Korponay‐Szabo^34,35, Sara Lega³⁶, Maureen Leonard³⁷, Edwin Liu³⁸, Eva Martinez³⁹, Mario Masic⁴⁰, Sasha Mealing⁴¹, Carolijn Meijer⁴², Zrinjka Mišak⁴⁰, Alexandra Papadopoulou⁴³, Alina Popp^44,45, Tatiana Raba⁴⁶, Carmen Ribes‐Koninckx^47,48, Firas Rinawi^49,50, Yasin Sahin⁵¹, Olof Sandström⁵², Naire Sansotta⁵³, Natalia Shapovalova⁵⁴, Anna Szaflarska‐Popławska⁵⁵, Peter Szitányi⁵⁶, Ulas Emre Akbulut⁵⁷, Vaidotas Urbonas⁵⁸, Badalyan Vahe⁵⁹, Francesco Valitutti⁶⁰, Margreet Wessels⁶¹, Jernej Dolinsek^1,62, Courtney Carter⁶³

¹Department Of Pediatrics, Gastroenterology, Hepatology And Nutrition Unit, University Medical Center Maribor, Maribor, Slovenia, ²Paediatric Gastroenterology Hepatology And Nutrition Unit, Academic Clinical Center (2CA Braga), Hospital de Braga, Braga, Portugal, ³Prince Abdullah Bin Khalid Coeliac Disease Research, Faculty of medicine, Department of pediatrics college of medicine King Saud University, Riyadh, Saudi Arabia, ⁴European Laboratory For The Investigation Of Food Induced Diseases (elfid), Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ⁵Pediatric Gastroenterology, Zeynep Kamil Women and Childrens Training and Research Hospital, University Health sciences, IstanbuL, Turkey, ⁶Pediatric Gastroenterology Institute, "Dana‐Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Affiliated to the Tel Aviv University Faculty of Medicine, Tel Aviv, Israel, ⁷Department Of Pathom*orphology, The Children's Memorial Health Institute, Warsaw, Poland, ⁸Pediatric Department, Mother & Child University Hospital El Eulma, University of Setif 1, Setif, Algeria, ⁹Harvard Medical School, Boston, United States of America, ¹⁰Division Of Gastroenterology And Nutrition, Boston Children's Hospital, Boston, United States of America, ¹¹Pediatric Gastroenterology Unit. Puerta de Hierro Majadahonda Hospital, Madrid, Spain, ¹²ADViSE Research Group. Department of Health Science, European University Miguel de Cervantes, Valladolid, Spain, ¹³Nutrition and Obesity Unit. Hospital Recoletas Campo Grande, Valladolid, Spain, ¹⁴Department Of Paediatrics, University of Otago, Christchurch, New Zealand, ¹⁵Paediatric Gastroenterology, Christchurch Hospital, Christchurch, New Zealand, ¹⁶Clinical Centre of Montenegro, Institute for Children's Disease, Podgorica, Montenegro, ¹⁷Department Of Gastroenterology, University Children's Hospital, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, ¹⁸Colorado Center For Celiac Disease, University of Colorado School of Medicine, Children's Hospital Colorado, Denver, CO, United States of America, ¹⁹Gastroenterology, Republican Specialized Scientifical Practical Medical Center of Pediatrics, Tashkent, Uzbekistan, ²⁰Gi Department, Royal Hospital For Children and Young People (RHCYP), Edinburgh, United Kingdom, ²¹Wilhelmina Ziekenhuis Assen, Assen, Netherlands, ²²Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, ²³Department Of Pediatrics, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Katowice, Poland, ²⁴Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel, ²⁵Coeliac Centre, Heim Pál National Paediatric Institute, Budapest, Hungary, ²⁶Medical University of Graz, Graz, Austria, ²⁷Pediatric Gastroenterology, Inonu University, Faculty of Medicine, Malatya, Turkey, ²⁸Stanford University School of Medicine, Stanford, CA, United States of America, ²⁹Department Of Pediatrics, Division Of Pediatric Gastroenterology, Hepatology, And Nutrition, Stanford Medicine Children's Health Center for IBD and Celiac Disease, Stanford, CA, United States of America, ³⁰Department Of Gastroenterology, Hepatology And Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia, ³¹Department Of Pediatrics, Medical University Prof. Dr Paraskev Stoyanov, Varna, Bulgaria, ³²Pediatric Gastroentrology, Kaplan Medical Center, Rehovot, Israel, ³³Faculty Of Medicine, Hebrew University of Jerusalem, jerusalem, Israel, ³⁴Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary, ³⁵Dept. Of Paediatrics, University Of Debrecen, Debrecen, Hungary, ³⁶Gastroenterology, Digestive Endoscopy And Nutrition Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy, ³⁷Center For Celiac Research And Treatment, Mass General Hospital for Children and Division of Pediatric Gastroenterology, Harvard Medical School, Boston‐Massachusetts, United States of America, ³⁸Colorado Center For Celiac Disease, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, United States of America, ³⁹Department Of Pediatric Gastroenterology And Nutrition, La Paz University Hospital, Madrid, Spain, ⁴⁰Referral Center For Pediatric Gastroenterology And Nutrition, Children's Hospital Zagreb, Zagreb, Croatia, ⁴¹Gastroenterology, Hepatology And Liver Transplant Unit, Children's Health Queensland Hospital and Health Service, Queensland Children's Hospital, South Brisbane, Australia, ⁴²Department Of Pediatric Gastroenterology, Leiden University Medical Centre, Willem Alexander Children's Hospital, Leiden, Netherlands, ⁴³Division Of Gastroenterology And Hepatology, First Department Of Pediatrics, University Of Athens, Children's Hospital Agia Sofia, Athens, Greece, ⁴⁴National Institute for Mother and Child Health "Alessandrescu‐Rusescu", Bucharest, Romania, ⁴⁵Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, ⁴⁶Department Of Pediatrics, "Nicolae Testemitanu" State University of Medicine and Pharmacy, Chisinau, Moldova, ⁴⁷Department Of Pediatric Gastroenterology, La Fe University Hospital, Valencia, Spain, ⁴⁸Coeliac Disease And Immunopathology Unit, Hospital La Fe Research Institute, Valencia, Spain, ⁴⁹Pediatric Gastroenterology Unit, Emek Medical Centre, Afula, Israel, Faculty of Medicine, Technion, Afula, Israel, ⁵⁰Pediatric Gastroenterology Unit, Emek medical center & The Ruth and Bruce Rappaport Faculty of Medicine, Afula, Israel, ⁵¹Division of Pediatric Gastroenterology, Gaziantep Islam Science and Technology University Medical Faculty, Gaziantep, Turkey, ⁵²Department Of Pediatrics, Department of Clinical Sciences, Umeå, Sweden, ⁵³Paediatric Hepatology Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy, Bergamo, Italy, ⁵⁴Saint Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation, ⁵⁵Department Of Paediatric Endoscopy And Gastrointestinal Function Testing, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland, ⁵⁶Dept. Of Paediatrics And Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic, ⁵⁷Pediatric Gastroenterology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey, ⁵⁸Clinic of Children's Diseases of Vilnius University Faculty of Medicine, Vilnius,, Lithuania, ⁵⁹Children's National Hospital, Washington, DC, United States of America, ⁶⁰Pediatric Clinic, Department Of Surgical And Biomedical Sciences, University of Perugia, Perugia, Italy, ⁶¹Department Of Pediatrics, Rijnstate Hospital, Arnhem, Netherlands, ⁶²Department Of Pediatrics, University of Maribor, Faculty of Medicine, Maribor, Slovenia, ⁶³Pediatrics, Division Of Gastroenterology, Hepatology & Nutrition, UCSF Benioff Children's Hospitals Mission Bay|Oakland, San Francisco, United States of America

Objectives and Study: The ESPGHAN Celiac disease Special interest group proposed the option of diagnosing coeliac disease (CD) without duodenal biopsy under specific conditions in 2012 and again in 2020. The current study aimed to evaluate the global adoption of this approach in children newly diagnosed with CD.

Methods: In a retrospective multi‐center study performed within the CD in Focus project, involving pediatric gastroenterologists from 29 countries worldwide (Europe, North America, Asia, North Africa, Australasia), medical data from children with CD diagnosed since 2021 was analyzed. Focus of this study was diagnostic approach, particularly the frequency of using the no‐biopsy approach. We compared diagnostic methods between countries participating in the EU CD SKILLS project and the others.

Results: Including data from 1925 newly diagnosed children with CD (63.3% female; median age 7.5 years) across 29 countries, our study found that the no‐biopsy approach was used in 47.3% (N=910) of cases, with 64.9% (N=591) meeting all criteria (TGA>10xULN, 2^nd EMA positive). Among 1015 biopsy‐diagnosed children (97.1% Marsh 2 or 3), 36.5% (N=371) would have been eligible for the no‐biopsy approach based on high TGA levels. The no‐biopsy approach was more prevalent in countries involved in CD SKILLS project compared to others (65.4% vs 38.0%; p<0.001). In the USA, where existing guidelines do not support the no‐biopsy approach, 15% of patients were nevertheless diagnosed without duodenal biopsy, while an additional 48.4% of biopsied children met the ESPGHAN criteria for the no‐biopsy approach.

Conclusions: Our study highlights a significant adoption of the no‐biopsy approach for diagnosing CD in children and adolescents, particularly in countries where awareness campaigns regarding the ESPGHAN guidelines have been actively conducted. Notably, the use of the no‐biopsy approach is gaining recognition as a valued diagnostic method in the United States, despite their respective guidelines that currently do not endorse this approach.

Contact e‐mail address: petra.riznik@gmail.com

INTESTINAL ORGANOIDS OF CHILDREN WITH DOWN SYNDROME AND VILLOUS ATROPHY SHOW ALTERATIONS IN VESICULAR TRAFFICKING AND INFLAMMATION WITHOUT SPECIFIC MARKERS OF CELIAC DISEASE

Roberta Rotondo^1,2, Claudia Bellomo³, Martina Carpinelli³, Francesca Furone³, Antonella Izzo⁴, Simona Paladino⁴, Mariantonia Maglio^1,5, Lucio Nitsch^4,6, Renata Auricchio^1,5, Riccardo Troncone^1,5, Maria Vittoria Barone^3,5, Merlin Nanayakkara^3,5

¹Department Of Translational Medical Science, Section Of Pediatrics, University of Naples "Federico II", Naples, Italy, ²Pediatric Clinic, University Hospital, Department Of Medicine And Surgery, University of Parma, Parma, Italy, ³Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ⁴Department Of Molecular Medicine And Medical Biotechnology, University of Naples "Federico II", Naples, Italy, ⁵European Laboratory For The Investigation Of Food Induced Diseases (elfid), Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy, ⁶National Research Council, Institute of Experimental Endocrinology and Oncology "G. Salvatore", Naples, Italy

Objectives and Study: Down Syndrome patients (DS) face a sixfold higher risk of Celiac Disease (CD) than the general population. Recent studies revealed duodenal histopathological alterations in half of DS patients with gastrointestinal symptoms, mostly attributable to villous atrophy (VA). In 28%, VA was not associated with CD; in 13%, neither symptoms nor intestinal lesions were gluten‐dependent. Cells from patients with CD or DS exhibited alterations in vesicular trafficking, leading, in CD, to inflammation and an increased response to gluten. This study aims to explore, using intestinal organoids, how modifications in the endocytic pathway in DS, without specific CD autoimmunity, may contribute to inflammation and an increased response to gluten.

Methods: Genetic testing for CD‐associated HLA‐DQ2/DQ8 and measurement of specific IgA autoantibodies (anti‐tissue transglutaminase, anti‐endomysium) were performed. IgA deficiency was excluded. Patients with gastrointestinal symptoms and/or positive CD serology underwent esophagogastroduodenoscopy. The karyotype of DS patients’ intestinal stem cells was determined through fluorescence in‐situ hybridization on intestinal organoids. Organoids were selected from 6 patients with active CD (CD), 3 with DS exhibiting VA not associated with CD (DS), and 6 controls (CTR). Levels of Early Endosome Antigen‐1 (EEA1) and pNF‐KB were assessed by Western Blot. Student's t‐test was used for statistical analysis (p<0.05)

Results: DS, negative for CD‐markers, showed trisomy 21 in intestinal stem cells. DS organoids exhibited alterations in the early endocytic pathway and inflammation, presenting elevated EEA1 and pNF‐KB levels, similar to CD (Figure‐1). Furthermore, CD organoids demonstrated a response to lower gluten peptide concentrations compared to CTR.

Conclusions: DS organoids show inflammation probably linked to defects in vesicular trafficking even in the absence of typical CD‐markers. Further research is needed to understand the link between intestinal inflammation, endocytic pathway alterations, and DS‐related cognitive impairment. Identifying gluten response or other pro‐inflammatory triggers, using intestinal organoids, could improve patient selection, diagnostic accuracy and targeted treatment.

Contact e‐mail address: robertarot.97@gmail.com

CHILDREN OF ERITREAN ASYLUM‐SEEKERS WITH CELIAC DISEASE HAVE SLOWER DECLINE IN ANTI‐TISSUE TRANSGLUTAMINASE ANTIBODIES COMPARED TO NATIVE‐BORN ISRAELI CHILDREN

Anat Yerushalmy‐Feler, Ittai Mani, Shlomi Cohen

Pediatric Gastroenterology Institute, Tel Aviv Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Objectives and Study: Adherence to gluten‐free diet (GFD) in celiac disease (CD) may be influenced by socioeconomic factors and language barriers. The study aimed to compare the course and outcomes of CD in children of Eritrean asylum‐seekers living in Israel to native‐born Israeli children.

Methods: A retrospective case‐control study, including all Eritrean children and native‐born Israeli children who were diagnosed with CD during 2015‐2023. For each Eritrean child, five consecutive native‐born Israeli children were included as controls. Demographic, clinical, laboratory, endoscopic and histologic data were retrieved.

Results: The study included 132 children: 22 Eritrean and 110 controls. Eritrean children were diagnosed with CD at a younger age [median 5.6 (4.3‐7.3) vs. 7.4 (4.9‐11.2) years, P=0.039]. Iron‐deficiency anemia was more prevalent in the Eritrean group (46% vs. 19%, P=0.008), with a median serum hemoglobin of 9.6 (6.7‐12.3) vs. 12.4 (11.5‐13.2) g/dL, P=0.006. A higher percentage of children in the Eritrean group (77% vs. 50%, P=0.017) exhibited anti‐tissue transglutaminase (TTG) antibodies >10 times above the upper limit of the normal (ULN) at diagnosis. Over a 12‐months of follow‐up under GFD, more Eritrean children maintained elevated anti‐TTG antibodies >10 times above the ULN compared to controls (43% vs. 1.4%, P<0.001]. A multivariate analysis indicated a greater likelihood of achieving normalization of anti‐TTG antibodies in the controls compared to the Eritrean group (OR=4.97, 95% CI 1.17‐21.13, P=0.030).

Conclusions: Children of Eritrean asylum‐seekers diagnosed with CD in Israel have a slower decline in anti‐TTG antibodies compared to native‐born Israeli children. Implementing an intervention program aimed to improve adherence to a GFD may positively impact the outcome of CD in this population.

Contact e‐mail address: ANATY11@YAHOO.COM

ELEVATED ISLET AUTOANTIBODIES IN CYSTIC FIBROSIS: IMPLICATIONS FOR EARLY SCREENING AND MANAGEMENT

Regina Molnár^1,2, Blanka Bódy^1,2, Réka Tóth¹, Tamás Kói¹, Klementina Ocskay², Andrea Párniczky^2,3