Dr. Jutta Kögelmeier, trained in Germany and the UK, is the clinical lead for nutrition and intestinal-failure rehabilitation at Great Ormond Street Hospital for Sick Children.

Together, Dr. Verduci and Dr. Kögelmeier focus on vegan and vegetarian diets in childhood, examining their effects on growth, nutritional adequacy, and health outcomes compared with omnivorous diets. They provide guidance for clinicians and families on monitoring and supporting children and adolescents adopting plant-based diets.

Selected Literature:

• Koller A et al. Health aspects of vegan diets among children and adolescents: A systematic review and meta-analyses. Crit Rev Food Sci Nutr 2024;64(33):13247–13258.

• Melina V et al. Position of the Academy of Nutrition and Dietetics: Vegetarian diets. J Acad Nutr Diet 2016;116(12):1970–1980.

• Neufingerl N, Eilander A. Nutrient intake and status in children and adolescents consuming plant-based diets compared to meat-eaters: A systematic review. Nutrients 2023;15(20):4341.

  Dr. Verduci & Koegelmeier´s favourite song:  Viva La Vida - Coldplay

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Her work focuses on dietetic care for children with obesity, particularly exploring the potential links between obesity and neurodevelopmental disorders, including autism. She investigates how aspects of neurodevelopmental disorders may contribute to obesity in children and provides practical guidance on managing their diets clinically.

Selected Literature:

• Sammels O et al. Autism spectrum disorder and obesity in children: A systematic review and meta-analysis. Obes Facts 2022;15(3):305–320.

• Mathew NE et al. Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles. Autism Res 2022;15(10):1824–1839.

• Hawton K et al. Complications of excess weight seen in two tier 3 paediatric weight management services: An observational study. Arch Dis Child 2025;110(3):216–220.

  Dr. Walker´s favourite song: Wish You Were Here - Pink Floyd 

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Dr. van der Doef emphasizes the importance of multi-institutional collaborations and supranational registries to understand the factors that influence clinical outcomes. Using data from the HEPATIC and PORTAL registries, supported by Delphi analysis, he contributes to developing standardized core outcome sets and evidence-based clinical guidelines for managing vascular complications in pediatric liver transplantation.

Selected Literature:

• de Ville de Goyet J et al. European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children. Hepatology 2022;75(3):634–645.

• Stevens JP et al. Portal vein complications and outcomes following pediatric liver transplantation: Data from the Society of Pediatric Liver Transplantation. Liver Transpl 2022;28(7):1196–1206.

• Li W et al. Treatment strategies for hepatic artery complications after pediatric liver transplantation: A systematic review. Liver Transpl 2024;30(2):160–169.

  Dr. Van der Doef´s favourite song: Joost Klein - Europapa

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

When he stepped down from that position, what had marked every other caesura in his professional life occurred once again: he was simply too good to let wander away. He now serves as consultant and emeritus professor within the same complex of institutions in which he has spent fifty highly productive years.

Prof Vandenplas has led the recent work of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications, addressing the supplementation of infant formula with biotics, including prebiotics, probiotics, postbiotics, synbiotics, and manufactured human milk oligosaccharides. These efforts have resulted in a series of technical reviews and recommendations that are poised to serve as practical clinical guidelines; the bibliographic list appears below.

He challenges listeners: with this literature as your guide, would you recommend adding “biotics” to infant formula—and why or why not? Which biotics would you choose? And with regard to human milk oligosaccharides, do you believe a “more-is-better” shotgun approach is preferable, or should specific oligosaccharides be selected and modified to address allergy risk or to mirror shifts in breast milk composition as the infant ages?

In short, the future is already here, and caregivers would do well to keep pace.

Titles

Recommendations on the Health Outcomes of Infant Formula Supplemented with Bioticsby the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications

Technical Review by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications on the Health Outcomes of Infant Formula Supplemented with Postbiotics

Literature

Dinleyici EC et al. Technical review by the ESPGHAN special interest group on gut microbiota and modifications on the health outcomes of infant formula supplemented with probiotics. J Pediatr Gastroenterol Nutr. 2025 May 12. doi: 10.1002/jpn3.70068. Online ahead of print. PMID: 40356343.

Hojsak I et al. Technical review by the ESPGHAN special interest group on gut microbiota and modifications on the health outcomes of infant formula supplemented with manufactured human milk oligosaccharides. J Pediatr Gastroenterol Nutr. 2025 Mar 24. doi: 10.1002/jpn3.70032. Online ahead of print. PMID: 40123480.

Mihatsch W et al. Technical review by the ESPGHAN special interest group on gut microbiota and modifications on the health outcomes of infant formula supplemented with prebiotics. J Pediatr Gastroenterol Nutr. 2025 May 19. doi: 10.1002/jpn3.70064. Online ahead of print. PMID: 40384260.

Salvatore S et al. Technical review by the ESPGHAN special interest group on gut microbiota and modifications on the health outcomes of infant formula supplemented with synbiotics. J Pediatr Gastroenterol Nutr. 2025 Mar 21. doi: 10.1002/jpn3.70031. Online ahead of print. PMID: 40114538.

Dr. Vandenplas´s favourite song: Louis Neefs - Wat Een Leven

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Among the “we,” and our lodestar, is Dr Jake Mann. He’s selected two articles for consideration: From Jezequel M et al., in work done at Lille, J Pediatr Gastroenterol Nutr brings us – Splenic stiffness does not predict esophageal varices in children with portal hypertension; and from a cluster of Parisian institutions, by Grimaud E et al. and published in Hepatology – Serum bile acid levels predict the development of portal hypertension and high-risk esophageal varices following successful Kasai in biliary atresia. In short: How to foretell the variceal future.

What sorts of cohorts were assembled, and what data were collected? How were those data analysed? All-comers in Lille, in Paris persons with a certain disorder treated in a certain way with a certain age and meeting certain clinical criteria… A lot to sort out here, and the comparisons and contrasts are better listened to than read, you’ll agree. Or:

Back to Sondheim, in the tale of Sweeney Todd, the demon barber of Fleet Street, who shaved the faces of gentlemen / Who never thereafter were heard of again…

What happened next?Well, that’s the play –And he wouldn’t want us to give it away.

Happy listening! Enjoy ESPGHAN Journal Club – enjoy the play!

Literature

Grimaud E et al. Serum bile acid levels predict the development of portal hypertension and high-risk esophageal varices following successful Kasai in biliary atresia. Hepatology 2025 Oct 23. DOI: 10.1097/HEP.0000000000001592. Online ahead of print. PMID: 41129338

Jezequel M et al. Splenic stiffness does not predict esophageal varices in children with portal hypertension. J Pediatr Gastroenterol Nutr 2026 Jan; 82(1):156–164. DOI: 10.1002/jpn3.70247. Epub 2025 Oct 27. PMID: 41144851. PMCID: PMC12780471

Dr. Tzivinikos shares his expertise on foreign-body ingestion in children, focusing particularly on button batteries and rare-earth magnets. This discussion addresses three key questions: How dangerous are rare-earth magnets? When and how should ingested magnets be removed? Are current efforts sufficient for advocacy and awareness?

Literature

• Online course – Paediatric Gastroenterology: Management of Foreign Body Ingestion in Children: https://www.futurelearn.com/courses/paediatric-gastroenterology-management-of-foreign-body-ingestion-in-children/1

• Nugud A et al. Pediatric magnet ingestion, diagnosis, management, and prevention: A European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper. J Pediatr Gastroenterol Nutr. 2023 Apr 1;76(4):523-532. doi: 10.1097/MPG.0000000000003702. Epub 2023 Mar 22. PMID: 36947000

• Furlano RI et al. Mistakes in paediatric foreign body ingestion and how to avoid them. UEG Education. 2024;24:1-7. Non-indexed journal.

  Dr. Tzivinikos´s favourite song: Theodorakis ‘s song - Aprilis

  ESPGHAN favourite songs can be found on Spotify: https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Following his studies, he conducted research in paediatric immunology in Leipzig before spending three years at the Sir William Dunn School of Pathology in Oxford. He later returned to Leipzig to work in paediatrics from 2004 to 2010, then returned to Oxford, where he currently serves as Professor of Paediatric Gastroenterology and Director of the Centre for Human Genetics.

Dr. Uhlig’s foundational work, completed during his first stay in Oxford, identified interleukin-23 as a key promoter of intestinal inflammation. This discovery has enabled the development of therapies targeting the alpha subunit of interleukin-23, modulating mucosal inflammatory activity. His team continues to unravel the complex pathophysiology of inflammatory bowel disease (IBD), using molecular-genetic analysis to identify monogenic contributions. Their ultimate goal is to develop genetics-based, patient-specific therapies.

Dr. Uhlig suggests correlated reading (see below) and invites reflection on key questions: What is the genetic basis of inflammatory bowel disease? How can research in genetics and immunology improve patient care? What are the most exciting recent developments in the field?

Literature

• Bolton C et al. An integrated taxonomy for monogenic inflammatory bowel disease. Gastroenterology. 2022 Mar;162(3):859-876. doi: 10.1053/j.gastro.2021.11.014. Epub 2021 Nov 13. PMID: 34780721. PMCID: PMC7616885; erratum, Gastroenterology. 2022 Jun;162(7):2143. doi: 10.1053/j.gastro.2022.04.007. Epub 2022 Apr 11. PMID: 35421357

• Kammermeier J et al. Genomic diagnosis and care coordination for monogenic inflammatory bowel disease in children and adults: Consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):271-286. doi: 10.1016/S2468-1253(22)00337-5. Epub 2023 Jan 9. PMID: 36634696

• Griffin H et al. Neutralizing autoantibodies against interleukin-10 in inflammatory bowel disease. N Engl J Med. 2024 Aug 1;391(5):434-441. doi: 10.1056/NEJMoa2312302. PMID: 39083772. PMCID: PMC7616361

  Prof Uhlig´s favourite song: J.S. Bach – Suite Nr. 1 für Violoncello Solo in G-Dur

  ESPGHAN favourite songs can be found on Spotify:https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

• Could you explain what a food ladder is?

• What steps does a child typically go through during the food ladder process?

• What are the key benefits of milk and egg reintroduction for patients and families?

• What positive outcomes do you observe clinically?

• At the same time, what are the most common barriers and facilitators to successful reintroduction, and how important is it to monitor each step of the ladder carefully to ensure safety and build confidence in both the child and the caregivers?

• As a dietitian, what practical advice would you give to clinicians conducting an oral food challenge with baked milk or egg? For example, how can existing recipes be adapted to match a child’s individual food preferences or their stage of oral-motor development?

• What would you suggest if a child with a food allergy is also a picky eater or has multiple food allergies – such as to both milk and wheat?

Below are references she has selected to guide listeners in addressing these questions.

Literature

• Venter C et al. Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP – an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin Transl Allergy. 2017 Aug 23;7:26. doi: 10.1186/s13601-017-0162-y. eCollection 2017. PMID: 28852472; cf. also Correction to: Venter C et al. Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP – an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin Transl Allergy. 2018 Jan 25;8:4. doi: 10.1186/s13601-017-0189-0. eCollection 2018. PMID: 29416848

• Meyer R et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update – VII: Milk elimination and reintroduction in the diagnostic process of cow's milk allergy. World Allergy Organ J. 2023 Jul 24;16(7):100785. doi: 10.1016/j.waojou.2023.100785. eCollection 2023 Jul. PMID: 37546235. PMCID: PMX10401347

• Gibson V et al. Barriers and enablers of dietary reintroduction following negative oral food challenge: A scoping review. J Allergy Clin Immunol Pract. 2025 Apr;13(4):851-860.e7. doi: 10.1016/j.jaip.2025.01.012. Epub 2025 Jan 17. PMID: 39828135

  Dr. Stróżyk´s favourite song is: Małomiasteczkowy - Dawid Podsiadło

  ESPGHAN favourite songs can be found on Spotify: https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Today’s note accompanies an encounter with Dr Elin Malmberg Hård af Segerstad, whose principal interests lie in the origins and management of the immune dysregulation manifest as coeliac disease.

In a person with an inherited susceptibility to coeliac disease, what triggers the development of that disease? Can triggers be avoided, and if so, how? After diagnosis and treatment, how can a patient with coeliac disease be monitored for compliance with dietary regimens? Who is best positioned to monitor such patients?

Dr Hård af Segerstad poses questions on three points as an armature for discussion:

1. What rôle does diet play in the development of coeliac disease in children? Can dietary modifications prevent coeliac disease?

2. How can gluten-free diet adherence be best assessed in children with coeliac disease? How does clinical practice at present fall short in this regard?

3. What is the rôle of the dietitian in the management of coeliac disease in children? Should all children with coeliac disease have access to an experienced dietitian?

In addressing these questions, she builds on three articles listed below – consensus summaries of best practice. But she also goes into detail on particular aspects of dietetic care not covered in those articles, so listen carefully!

• Mearin ML et al. ESPGHAN position paper on management and follow-up of children and adolescents with celiac disease. J Pediatr Gastroenterol Nutr 2022 Sep 1; 75(3):369–386.Doi: 10.1097/MPG.0000000000003540. Epub 2022 Jun 27. PMID: 35758521

• Luque V et al. Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease. J Pediatr Gastroenterol Nutr 2024 Apr; 78(4):973–995.Doi: 10.1002/jpn3.12079. Epub 2024 Jan 30. PMID: 38291739

• Szajewska H et al. Early diet and the risk of coeliac disease: An update 2024 position paper by the ESPGHAN special interest group on coeliac disease. J Pediatr Gastroenterol Nutr 2024 Aug; 79(2):438–445.Doi: 10.1002/jpn3.12280. Epub 2024 Jun 7. PMID: 38847232

  Dr. Malmberg´s favourite song: Måns Zelmerlöw - Heroes

  ESPGHAN favourite songs can be found on Spotify: https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Well, readers, when this reaches you perhaps we shall all be in 2026, perhaps not; whichever, the New Year’s Eve couplet above may amuse you as you look backward, or forward, and… but who says that time has to be linear? Very twentieth-century idea, that – we’ve made progress since then. In any case, whenever this is, here we are.

ESPGHAN Journal Club isn’t like the seasons, like the years, going around and around and enough to make your head spin. Journal Club instead has one fixed, unmoving point around which everything revolves. Yes: the ultra-stable Dr Jake Mann. What has Ol’ Reliable, as he’s nicknamed, selected for us today?

Coeliac disease (CD) is on Jake’s menu – how to diagnose it, how to treat it. Treatment first. In Alimentary Pharmacology & Therapeutics, by Risnes LF et al., writing from a handful of institutions in Oslo: Teriflunomide does not affect gluten-specific T-cell activity in coeliac disease – a randomised, placebo-controlled trial; and then, in a blatant attempt to reduce histopathologists and endoscopists to diagnostic irrelevance and grinding poverty, from Journal of Pediatric Gastroenterology and Nutrition, by Mandile R et al., working in Naples and Rotterdam: A set of serum proteomic biomarkers differentiates celiac children from age- and human leukocyte antigen-matched healthy controls.

What, or who, is teriflunomide (“but you can call me Teri”)? Teri is an inhibitor of nuclear factor kappa–light-chain-enhancer of activated B cells (NF-κB), and she’s cytotoxic, albeit not very, which makes her valuable in dampening inflammatory activity. Teri can make activated T cells, in particular, go off the boil, which has won her a rôle in the treatment of multiple sclerosis. Risnes et al. hypothesised that she could usefully be deployed in CD.

To test this in 15 children with treated CD, Risnes and co-workers fed Teri to 10 and placebo to 5 for a week, after which a gluten challenge – a slice of white bread daily for three days – was administered, with Teri continued until the end of the second week. Serum levels of interleukin-2, an acute-response indicator, were determined in samples taken four hours after the first slice of white bread was eaten. On Day 15 of the study, eight days from the first day of the challenge, the team counted gluten-specific CD4+ T cells in blood (detected by HLA-DQ2.5:gluten tetramers) that bore the activation marker CD38, a longer-term response indicator, as well as CD103+CD38+ gut-homing CD8+ T cells and γδ T cells. Gluten challenge evoked substantial acute and longer-term inflammatory responses, but Teri administration yielded no difference between cohorts in values for any analyte.

Theseus in shadow, patting his way forward; at the end of the corridor, another doorless wall. The darkness, and the stench of the Minotaur, and the sick realisation – I must go back and try again. Risnes et al. have taken the Teri turning, have explored another arm of the labyrinth of how to modulate, how to understand, inflammation in CD, and met with not a doorless wall exactly; instead, a possibility assessed and found wanting. That is something. We learn that one set of ideas about CD is falsifiable. That is even something interesting. But the chagrin of acknowledging that we must go back and try again? We are Theseus.

Still in the CD labyrinth with Jake’s other choice; what is that at our feet? Bend, pick up, feel the embossed letters – χτῆμα Ἀριάδνης; “property of Ariadne”. Part-unreeled, a spool of thread! This may actually get us somewhere. Indeed, Mandile et al., our collective daughter of Minos, have sorted through serum biomarkers of inflammation and have given us a clew worth following, perhaps toward light and freedom.

That is, toward non-invasive diagnosis in CD that requires neither endoscopy nor mucosal biopsy. Assessments of the proteome in mucosal biopsy specimens have shown certain patterns of increases in inflammation-pathway members; Mandile et al. reviewed relative abundances of 92 such analytes in sera from 100 paediatric patients – 50 with active CD (45 documented by histopathologic study of biopsy specimens, 5 by high titres of anti-tissue transglutaminase antibodies [anti-TTA]) and 50 with HLA-DQ2/DQ8 “at-risk” phenotypes who did not have clinically manifest CD and who did not develop such CD over the nine years after serum sampling. The subjects were age-matched cohort to cohort and of similar ethnic background.

Three different statistical sievings yielded seven proteins (CASP8, CXCL9, NT-3, SIRT2, STAMBP, ST1A1, and TNFSF14) that, when present in abundance, distinguished approximately 90% of CD children from non-CD children. Current algorithms for diagnosis of CD, unless anti-TTA titres are very high, require endoscopy and mucosal biopsy with demonstration in the biopsy specimen of certain features. Might demonstration of a serum protein-abundance pattern like that determined to mark CD in the patients of Mandile et al. obviate endoscopy and biopsy in other patients?

To answer that question will require confirmation of this study’s findings in other cohorts of other ethnicities. Those are likely already under way. Even now, Theseus is rapidly rolling thread from the labyrinth’s floor onto Ariadne’s spool, following the clew toward a brighter future with many fewer invasive procedures in CD patients. Phlebotomy instead of endoscopy and biopsy; insights from cytokinome work into mechanisms of inflammation in CD; remarkable progress! Even with immiseration looming, paediatric endoscopists and histopathologists must concur in this assessment of what Mandile et al. have contributed with this study.

Literature

Mandile R et al. A set of serum proteomic biomarkers differentiates celiac children from age- and human leukocyte antigen-matched healthy controls. J Pediatr Gastroenterol Nutr. 2025 Nov 20. doi: 10.1002/jpn3.70261. Online ahead of print. PMID: 41263022.

Risnes LF et al. Research communication: Teriflunomide does not affect gluten-specific T-cell activity in coeliac disease – a randomised, placebo-controlled trial. Aliment Pharmacol Ther. 2025 Nov;62(10):1027–1031. doi: 10.1111/apt.70301. Epub 2025 Jul 27. PMID: 41124699.

He offers three clinical scenarios that involve Helicobacter pylori disease to Prof Dr Matjaž Homan for his perspective on diagnosis and treatment, in particular deployment of antibiotics. Prof Homan trained in Slovenia, taking his medical degree in Ljubljana, and has conducted academic work on H. pylori both there and in Zagreb (Croatia). He now in Ljubljana is the deputy director of the University Children’s Hospital.

In his comments on Dr Giamouris’ clinical vignettes he illustrates the principles set out in the recently updated ESPGHAN / NASPGHAN guidelines for physicians addressing H. pylori disease – guidelines for which he was the foremost reviser, and which are cited below.

LiteratureHoman M et al. Updated joint ESPGHAN / NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023). J Pediatr Gastroenterol Nutr 2024 Sep; 79(3):758-785. Doi: 10.1002/jpn3.12314. Epub 2024 Aug 15. PMID: 39148213

Dr. Homan´s favourite song: John Lennon - Give Peace a chance

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

We haven’t forgotten the allied professions, mind you; this note accompanies for you an encounter recorded at the 2025 ESPGHAN Annual Meeting with Dr Kathryn Bradley, a clinical psychologist expert in Avoidant/Restrictive Food Intake Disorder (ARFID).

Her work in “picky eating” is not her only credential in paediatric gastroenterology, hepatology, and nutrition: she is the mother of a child with total colonic aganglionosis, a lived experience on which she draws in counselling and treatment of children who, unlike most of us, cannot eat and drink unthinkingly... and of their families.

In this podcast, she addresses these three questions:

1. What are the key signs that distinguish ARFID from typical “picky eating” or other eating disorders?

2. How does ARFID affect a child's physical and mental health, and what are the long-term consequences if children and families are left without support?

3. What evidence-based approaches can be used to support a child/family with ARFID and which professionals should be involved?

In addressing these questions, she builds on two articles — gateways into resources to be consulted as caregivers encounter ARFID:

LiteratureBryant-Waugh R et al. Towards an evidence-based out-patient care pathway for children and young people with avoidant restrictive food intake disorder.J Behav Cogn Ther 2021; 31:15–26. (Non-indexed article)

Sanchez-Cerezo J et al. What do we know about the epidemiology of avoidant/restrictive food intake disorder in children and adolescents? A systematic review of the literature.Eur Eat Disord Rev 2023 Mar; 31(2):226–246.DOI: 10.1002/erv.2964 | Epub: 2022 Dec 16 | PMID: 36527163 | PMCID: PMC10108140

Dr. Bradley´s favourite song: Oasis - She is electric 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Jake has chosen two variations on a theme: IBD, or inflammatory bowel disease. From Lancet Gastroenterol Hepatol, by Atia O et al., in a collaboration that pinballs all over the map, from Jerusalem to Philadelphia to Ljubljana and beyond – Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study. Well! That will keep clinician listeners happy; and then, throwing your interviewer a histopathologic bone, from J Pediatr Gastroenterol Nutr, by Little R et al., of Toronto’s Hospital for Sick Children and the University of Toronto – Intestinal histopathology in pediatric PSC-IBD: Characterization of phenotype and assessment of the Nancy Index.

Vedolizumab – to its friends, Entyvio – is a monoclonal antibody that blocks the dimer LPAM-1, or lymphocyte Peyer’s patch adhesion molecule, more formally known as integrin α4β7. Blocking integrin α4β7 selectively dampens gut inflammation. Entyvio use has been approved in adults with IBD unresponsive to tumour necrosis factor blockade (adalimumab, infliximab, etc.) or to corticosteroids, or who are steroid-dependent. Formal approval for use in children has not been given, but, faute de mieux, it is deployed anyhow, with good results in two prospective studies of short-term use. Reports of long-term use in children, again with good results, exist, but they are not prospective.

The study by Atia et al. has addressed this, with assessment at baseline and after 2 wk, 6 wk, 14 wk, 30 wk, and 54 wk of administration in a 137-member cohort assembled over 6 y. Efficacy of Entyvio against paediatric IBD is good, with few adverse effects (week 54: complete remission, 25% of children with Crohn disease and 47% of children with ulcerative colitis). Noteworthy are that ulcerative-colitis patients responded better than did Crohn-disease patients and that response by 6 wk or 14 wk predicted sustained response – the latter observation suggests that failure to respond to the dosage regimen used in the studied patients may warrant adjustment of that regimen. In sum, the study supports longer-term use of Entyvio in children with IBD.

One wonders what genetic quirks may correlate with good or poor early response to Entyvio. Perhaps the samples to answer this question are in someone’s freezers…

Medicine wants desperately to be scientific, and believes with all its heart that quantification means Science. From this – well, is it a fallacy? Opinions will vary – from this stance, at any rate, this stance that holds that without a Number evaluation is, as Science, inadequate, derive protocols for grading, and for staging, and for scoring. In histopathologic work these are beautifully suited to retrospective studies, studies in which one person at one time evaluates a large cohort of specimens using detailed criteria, with grade and stage and score interacting to yield Numbers.

Are the resulting Numbers reliable? Does the same histopathologist’s work yield the same Numbers every time for the same specimens (“intraoperator variation”)? Does different histopathologists’ work yield the same Numbers every time for the same specimens (“interoperator variation”)? Can Numbers for different specimens obtained from the same patient at different times by different individual histopathologists be trusted to reflect evolution in that patient’s disease – “She was a Seven a year ago, as scored by Joe, on treatment she’s now a Six, as scored by Mary, so the therapy must be working”? Perhaps artificial intelligence, applied universally, will prove its worth in such settings. To mis-quote Tolkien:

One programme to rule them all,one programme and no more,one programme to read them alland uniformly score.

Toward the value of grading, staging, and scoring outside a retrospective study, however – that is, in everyday service work performed non-uniformly by a variety of humans – scepticism seems appropriate.

In IBD, several scoring systems have been proposed, and modified, and used. (That several exist bears witness to the inadequacy of all.) Easiest to deploy is that proposed by workers in Nancy (France), the “Nancy index”. Little et al. conducted Nancy indexing in endoscopic mucosal-biopsy specimens from children with IBD associated with primary sclerosing cholangitis (PSC; 50 subjects) and with IBD independent of PSC (81 subjects), proceeding from observations that the clinical and endoscopic features of IBD tout court and of PSC-IBD vary.

In the setting of their retrospective study, “Nancy index” values were reproducible between observers – to some extent trustworthy Numbers, then – and differences existed between histopathologic findings in the two cohorts, suggesting a PSC-IBD histopathologic phenotype. This is not surprising; if rectal sparing, predominantly right-sided colonic inflammation, and “backwash” ileitis clinically and endoscopically characterise PSC-IBD, some sort of histopathologic counterpart to inflammation or to the lack thereof can be expected. Of note, however, is that three features – lamina-propria neutrophil-leucocyte infiltration, eosinophil-leucocyte infiltration, and surface villiform change – were more prominent in PSC-IBD. Perhaps these aspects, not addressed in the grading, staging, and scoring systems used generally in IBD, should be given attention in paediatric IBD patients, and perhaps they point toward pathophysiologic differences between IBD and PSC-IBD that are worth study. Whether Nancy indexing, or modified paediatric-IBD Nancy indexing, will yield Numbers that convey detailed, both diagnostically and prognostically salient information in prospective work, or in routine clinical care, is still very much an open question.

Literature

Atia O et al. Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study. Lancet Gastroenterol Hepatol 2025 Mar;10(3):234-247. Doi: 10.1016/S2468-1253(24)00319-4. Epub 2025 Jan 6. PMID: 39788134

Little R et al. Intestinal histopathology in pediatric PSC-IBD: Characterization of phenotype and assessment of the Nancy Index. J Pediatr Gastroenterol Nutr 2025 Feb;80(2):290-299. Doi: 10.1002/jpn3.12434. Epub 2024 Dec 17. PMID: 39690834. PMCID: PMC11788967

Ms. Norris trained as a dietitian – went slightly off-piste with two years of education in youth work and theology – and thereafter specialised first in paediatric nutrition and then, for the last fifteen years, in neonatal nutrition, working particularly in the last five of those years with the complicated patients born prematurely or having undergone surgical modification of the gut.

She shares today her insights into approaches to those patients’ care, addressing these questions:

• What are particular nutritional challenges following surgery in neonates?

• How does one know when to re-start nutrition, what feeds to choose, and how best to advance nutrition after gastrointestinal surgery in neonates?

• In what does effective management consist, yielding optimal outcomes for families and infants?

Literature

• Penman G et al. Neonatal feeding: Care and outcomes following gastrointestinal surgery. Infant 2017; 13(2):61–64. Non-indexed journal.

• Framework for practice: Holistic feeding and nutritional management for the near term/term neonate, following bowel surgery. June 2004. Sponsored by The National Neonatal Surgical Interest Group (NNSIG) of the Neonatal Nurses Association, Dartford, UK. Accessioned 2025.V.05 at: https://nna.org.uk/wp-content/uploads/2024/09/Framework-for-Practice_NNSIG-V7.pdf

• Mo I et al. Nutritional management after necrotizing enterocolitis and focal intestinal perforation in preterm infants. Pediatr Res 2024 Jul 11. doi: 10.1038/s41390-024-03386-y. Online ahead of print. PMID: 38992154

Heather Norris’s favourite song: Elbow – One Day Like This

ESPGHAN favourite Songs can be found on Spotify: Spotify Playlist

They are experts in the nutritional dysregulation that results from cystic fibrosis, you see… Dr. Masip trained in Valencia and Catalonia, and now in Valencia heads the paediatric cystic-fibrosis unit at La Fe University and Polytechnic Hospital. Dr. Birimberg-Schwartz trained in Jerusalem and in Toronto, at the Hospital for Sick Children, and now, back in Jerusalem at Hadassah Medical Center, attends patients and conducts research into cystic fibrosis using organoids in culture.

The prospects for children with cystic fibrosis have been substantially improved by the complementary deployment of agents that alleviate dysfunction of variant cystic fibrosis transmembrane-conductance regulator (CFTR), with elexacaftor and tezacaftor shifting CFTR within the cell membrane to sites permissive for CFTR activity and ivacaftor potentiating that activity. Unfortunately, efficacy of the elexacaftor–tezacaftor–ivacaftor (ETI) combination in modulating CFTR activity differs from variant to variant, but for many patients ETI appears to have improved both ventilatory and digestive quality of life.

In those patients for whom ETI means better nutrition, what are the consequences of its availability for the need to re-think recommendations for their care, particularly regarding dietary composition, growth monitoring, and follow-up protocols? Beyond weight gain, what real-life evidence supports the impression that gastrointestinal symptoms and inflammation are ameliorated in paediatric cystic-fibrosis patients (adolescents included) treated with ETI? Finally, does ETI therapy modify the natural course of cystic-fibrosis–related liver disease in children, and might it reduce the need for routine hepatologic surveillance in selected patients?

Dr. Birimberg-Schwartz and Dr. Masip, as was to be expected, carry the day. Enjoy listening to them and enjoy their expertise!

Literature

• Mainz JG et al. Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and calprotectin over one year of treatment with elexacaftor–tezacaftor–ivacaftor in people with CF aged ≥12 years – The RECOVER study. J Cyst Fibros 2024 May; 23(3):474–480. doi: 10.1016/j.jcf.2023.10.001. Epub 2023 Oct 7. PMID: 37806792

• Terlizzi V et al. Effect of elexacaftor–tezacaftor–ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis. J Cyst Fibros 2025 Jan 12:S1569-1993(24)01861-7. doi: 10.1016/j.jcf.2024.12.010. Online ahead of print. PMID: 39800644

• Wilschanski M et al. ESPEN–ESPGHAN–ECFS guideline on nutrition care for cystic fibrosis. Clin Nutr 2024 Feb; 43(2):413–445. doi: 10.1016/j.clnu.2023.12.017. Epub 2023 Dec 27. PMID: 38169175

Dr. Masip & Dr. Birimberg-Schwartz’s favourite song: The Beatles – Here Comes the Sun

ESPGHAN favourite Songs can be found on Spotify: Spotify Playlist

Jake’s choices for today: From J Pediatr Gastroenterol Nutr, by Anouti A. et al., writing from several USA institutions — Pediatric liver transplant outcomes: A comparative analysis of steatotic donor grafts. To follow, by Chu C. et al., from southern California under the palms of Los Angeles, and published in Hepatol Commun — Ultrasound of the rectus femoris as a novel tool to measure sarcopenia in pediatric chronic liver disease.

Be warned, prospective readers: although in neither selection do the authors squeeze cells and look at the juice — no pesky nucleic acids work! — you may want your hip boots: the statistics are scary deep.

Given that donor livers are growing fatter, the proportion of livers in which steatosis precludes use as an allograft may be increasing, Anouti et al. tell us. Adding to this, donor livers have never been abundant. The question posed: are outcomes substantially worse with fatty allografts than with lean allografts?

In the twenty years between 2004 and 2024, according to a USA liver transplantation database, 595 children and adolescents received liver allografts that were considered steatotic. In 62 (10.4%), steatosis affected >30% of parenchyma. Those recipients — in terms of one-year, five-year, and ten-year survival — fared no worse than did the other 533 with steatosis affecting <30% of parenchyma. This differs from what is observed in adults, who tolerate fatty implants poorly. In children, however, other factors conferred adverse prognosis. If those factors are borne in mind, and measures to address them are taken, the authors propose, fatty donor livers may be more widely usable.

Readers are not given several denominators: how many paediatric liver transplants took place overall? How many donor livers seemed dodgy enough to the surgical team that a histopathologist was called to evaluate a biopsy specimen? How many biopsied livers were discarded rather than implanted? And most importantly — what are survival rates in children who receive non-steatotic livers? To be regretted.

Chu and colleagues offer the results of imaging-study work intended to assess muscle bulk and consistency (fibrosis, fatty infiltration) in paediatric patients with chronic liver disease. Growth failure, they tell us, is not always reflected in paediatric end-stage liver disease scores that are used in selecting children for liver transplantation, and children not listed for transplantation but with growth failure not infrequently die while waiting for an organ.

Frailty and sarcopenia — lack of muscle mass — might, as indicators of growth failure, warrant consideration in juggling children up and down the transplantation list. What measurements, though, should one use in assessing muscle qualitatively and quantitatively? Where should measurements be taken?

Chu et al. subjected the rectus femoris, right and left, to ultrasonography, because that muscle is easy to find and easy to scan. They found that their measurements yielded internally and observer-to-observer consistent results, and that these results correlated well with clinical findings and clinical-laboratory biomarker values. Another arrow in the hepatologic quiver, then, and time will tell how often this new arrow is chosen to be nocked and shot — as well as how often, off the bowstring, it hits the intended target.

Two articles, two précis. But what does Jake think of these contributions to our literature? Why does he recommend that we grapple with them? Don’t click away — he’ll tell us.

Literature

Anouti A. et al. Pediatric liver transplant outcomes: A comparative analysis of steatotic donor grafts. J Pediatr Gastroenterol Nutr. 2025 Sep 22. DOI: 10.1002/jpn3.70213. Online ahead of print. PMID: 40977417

Chu C. et al. Ultrasound of the rectus femoris as a novel tool to measure sarcopenia in pediatric chronic liver disease.Hepatol Commun. 2025 Aug; 159(9): e0799. DOI: 10.1097/HC9.0000000000000799. PMID: 40824275. PMCID: PMC12363444

Her particular interest and expertise lie in intestinal failure and its therapies, with surgical short-bowel syndrome, paediatric intestinal pseudo-obstruction, and a variety of congenital enteropathies among the problems that she, her patients, and her patients’ families face together.

Listeners will learn her answers to five important questions:

1. What are the common causes for chronic intestinal failure in children other than surgical short-bowel syndrome?

2. What makes paediatric intestinal pseudo-obstruction or congenital enteropathies so challenging? Or, how do they differ from short-bowel syndrome?

3. Although life-saving for these patients, long-term parenteral nutrition comes with risks. What complications should clinicians anticipate?

4. What strategies are most effective in improving long-term outcomes?

5. What do we know about long-term outcomes and quality of life for these children?

She recommends the following articles for more comprehensive and detailed information than the interview could present.

Literature

• Duggan CP, Jaksic T. Pediatric intestinal failure. N Engl J Med 2017 Aug 17; 377(7):666–675. doi: 10.1056/NEJMra1602650. PMID: 28813225

• Lezo A et al. Chronic intestinal failure in children: An international multicenter cross-sectional survey. Nutrients2022 Apr 30; 14(9):1889. doi: 10.3390/nu14091889. PMID: 35565856. PMCID: PMC9103944

• Norsa L et al. Nutrition and intestinal rehabilitation of children with short bowel syndrome: A position paper of the ESPGHAN Committee on Nutrition. Part 2: Long-term follow-up on home parenteral nutrition. J Pediatr Gastroenterol Nutr 2023 Aug.

• Demirok A et al. Pediatric chronic intestinal failure: Something moving? Nutrients 2024 Sep 3; 16(17):2966. doi: 10.3390/nu16172966. PMID: 39275281. PMCID: 11397488

Dr. Guz’s favourite song: Yuval Raphael – New Day Will Rise

ESPGHAN favourite Songs can be found on Spotify: Spotify Playlist

In this episode, two physician-scientists who are among the registrars share their insights: Oanez Ackermann, of Le Kremlin–Bicêtre (Paris), and Tassos Grammatikopoulos, of King’s College Hospital (London). They address key questions:

• Why has a registry worthy of the name been so late in arriving?

• What are the registry’s goals?

• How can portal hypertension best be diagnosed non-invasively today, and what progress is expected in this area?

• How can pulmonary hypertension, a severe complication of portal hypertension, be best diagnosed?

Meaty stuff! For further details, you are referred to the articles listed below.

• El Koofy N et al. Prevalence and predictors of pulmonary hypertension in children with portal hypertension: A single center study. Pediatr Gastroenterol Hepatol Nutr. 2025 Mar; 28(2):101-112. Doi: 10.5223/pghn.2025.28.2.101. Epub 2025 Mar 5. PMID: 40109566. PMCID: PMC11919534

• Grammatikopoulos T et al. Considerations in the development of the International Multicenter Pediatric Portal Hypertension Registry. J Pediatr Gastroenterol Nutr. 2025 Jan; 80(1):197-202. Doi: 10.1002/jpn3.12415. Epub 2024 Nov 18. PMID: 39552494

• Rockey DC et al. Noninvasive liver disease assessment to identify portal hypertension: Systematic and narrative reviews supporting the AASLD Practice Guideline. Hepatology. 2025 Mar 1; 81(3):1086-1104. Doi: 10.1097/HEP.0000000000000841. Epub 2024 Mar 15. PMID: 38489516

Dr. Grammatikopoulos & Dr. Ackermann´s favourite song: Nina Simone – Feeling Good

ESPGHAN favourite songs can be found on Spotify: https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Thanks for tuning in to learn what Dr. Jake Mann thinks are the raisins in the loaf for this month.

Jake’s choices for today:

• Hoskins BJ et al. (Indianapolis, Indiana, USA), J Pediatr Gastroenterol Nutr – Pediatric endoscopic mucosal resection: A 10‐year single‐center experience.

• Kulecka M et al. (Cork and Galway, Ireland; Málaga, Spain; London; Utrecht), Nat Commun – Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis.

In what USAnians call “flyover country,” a ten-year review at a tertiary-care paediatric referral hospital included twenty mucosal or submucosal lesions treated by submucosal resection using cold- or hot-snare, banding, and underwater techniques. (Supplemental materials include videos of these resections.)

One lesion with fibrosis required surgical resection after endoscopic attempts. Otherwise, procedures were technically successful and well tolerated.

The authors have argued separately in J Pediatr Gastroenterol Nutr (link) for a discipline-wide reassessment of paediatric guidelines for endoscopic polypectomy. In their current report, they urge colleagues not to shy away from submucosal resection in children.

But questions remain: How should training be organized? How can enough cases be centralized so competence is maintained? Or, who will bell the cat? Problems for another day.

The authors frame their hypothesis clearly: not all children with ulcerative colitis (UC) respond to standard therapies. Could combined analysis of the mucosal microbiome, transcriptome, and epigenetic modifications predict which patients are at risk of relapse—allowing earlier use of second-line treatments?

Findings:

• Lower microbial diversity and depletion of butyrate-producing and mucin-degrading bacteria correlated with higher relapse risk.

• Colonisation of the distal bowel by oral flora—especially Veillonella dispar—marked a tendency for relapse. Similarly, V. parvula was overrepresented in relapsing patients.

• Functional studies in culture and mice showed pro-inflammatory effects not suppressed by standard UC therapies.

• Transcriptomic and epigenetic differences correlated with both microbiome composition and clinical course.

Conclusion: The authors propose that such analyses could identify children at higher risk of poor outcomes, emphasizing the novel predictive value of their approach. (Note: critical reading requires strong backgrounds in both statistics and microbiology—this is not light work!)

What do they signify for clinical practice and future research? Jake will tell us.

Departing from the bakeshop metaphor with which this commentary began, and paraphrasing from The Who’s rock opera Tommy:“With Jake as our leader, Jake as our guide / On the amazing journey together we’ll ride!”

Or, as Bette Davis (as Margo Channing in All About Eve) put it:“Fasten your seat belts – it’s going to be a bumpy night.”

Literature

• Hoskins BJ et al. Pediatric endoscopic mucosal resection: A 10‐year single‐center experience. J Pediatr Gastroenterol Nutr. 2025 Aug 12. Online ahead of print. doi:10.1002/jpn3.70194. PMID: 40798915

• Kulecka M et al. Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis. Nat Commun. 2025 Aug 4;16(1):7157. doi:10.1038/s41467-025-62533-z. PMID: 40759968. PMCID: PMC12322004

His training and early professional work were in Sarajevo, Bosnia-Herzegovina, but when he obtained a research fellowship in London, his supervisors soon recognised that he was too good to be allowed to return home.(For those who follow Croatian football: the centre-forward for Team Orijent in Sušak / Rijeka is a different Nedim Hadžić.)

Dino is now among the consultant hepatologists at King’s College Hospital, where he has cultivated an interest in alpha-1-antitrypsin storage disorder and circulating alpha-1-antitrypsin deficiency.(No, they’re not the same thing. We’ll blur the lines and henceforward refer to alpha-1-antitrypsin disease.)

He asks listeners today to think about:

• how alpha-1-antitrypsin disease may cause liver disease,

• how it may cause lung disease,

• why not all persons who harbour variants in SERPINA1 (which encodes alpha-1-antitrypsin) manifest clinical disease,

• and what can be done to treat severe liver disease associated with SERPINA1 variants.

He has provided a few references for us all, set out below.

Literature

• Francavilla R et al. Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. J Hepatol. 2000 Jun; 32(6):986-992. doi:10.1016/s0168-8278(00)80103-8. PMID: 10898319

• Hinds R et al. Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease. J Pediatr Gastroenterol Nutr. 2006 Jul; 43(1):136-138. doi:10.1097/01.mpg.0000226370.09085.39. PMID: 16819392

• Strnad P et al. Alpha1-antitrypsin deficiency. N Engl J Med. 2020 Apr 9; 382(15):1443-1455. doi:10.1056/NEJMra1910234. PMID: 32268028

• Clark VC et al. Fazirsiran for adults with alpha-1 antitrypsin deficiency liver disease: A phase 2 placebo-controlled trial (SEQUOIA). Gastroenterology. 2024 Oct; 167(5):1008-1018.e5. doi:10.1053/j.gastro.2024.06.028. Epub 2024 Jul 2. PMID: 38964420

  Dr. Hadzic´s favourite song: Indexi - Zute dunje

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Give us your full attention, please – even if that means pulling into a lay-by or, even more demanding, setting down your drink. The thoughts and insights of Dr. Jake Mann are deffo worth the trouble.

Jake’s choices for today:

• From J Pediatr Gastroenterol Nutr, by Tai CS et al., with authors from Taiwan, Thailand, and Korea: “A prediction model for genetic cholestatic disease in infancy using the machine learning approach.”

• From JCI Insight, by Arnson B et al., with authors from the United States and the United Kingdom: “Efficacious genome editing in infant mice with glycogen storage disease type Ia.”

Machine learning, gene therapy… Journal Club is, as always, out in front – where Jake keeps dragging us.

The contribution from Tai et al. postulates that genetic analysis in neonatal cholestasis without mechanical obstruction is expensive and, in many sites, difficult to access. It advocates screening for genetic analysis and reports the retrospective sifting of 47 parameters per patient with intrahepatic neonatal cholestasis (1008 patients in total!), 63 of whom were ultimately diagnosed with “genetic cholestasis” (GC).

Among the 47 parameters assessed at presentation and again one month later, 20 – not including sonographic findings – proved useful in tracking GC. The predictive utility of this combination was checked in 36 patients with GC and 62 without, from two other institutions. Overall, about 70% of patients were identified as unlikely to have GC and might have been spared genetic analysis. The authors propose the algorithm, devised via machine learning, as a cost-saving measure.

What does Jake think of all this? Listen and find out.

Clinical caregivers and biomedical researchers at Duke University, North Carolina (USA), have made something of a hobby of glycogen storage disorders (GSDs) – their causes and cures – including glucose-6-phosphatase (G6P) deficiency (GSD1a). Adeno-associated virus has been used as a vector in mice, dogs, and humans to deliver functional G6PC copies (“transgenes”) into hepatocytes and renal tubular epithelium. These encode the catalytic subunit of G6P, variants of which cause GSD1a.

Unfortunately, G6PC transgenes introduced into hepatocytes are episomal, and episomal G6PC is rapidly lost in model mice and dogs – particularly in infant mice. Repeated or increased transfection does not adequately compensate for this loss.

The Duke Blue Devils (not “Dookies,” please – only Tar Heels use that term!) have now used CRISPR/Cas9-based techniques in 12-day-old G6pc-/- mice to achieve “long-term” genomic integration of G6PC, with euglycaemia sustained at least to age 12 weeks. (One supposes that counts as “long-term” in a mouse.)

The crucial question: will this prevent development of hepatocellular adenomas and carcinomas that occur in untreated humans and in episomally treated, but euglycaemic, mice and dogs?

As the ESPGHAN Journal Club mantra rises from the musical background: More studies are required. More FUNDING is required.

At any rate, this is an intriguing glimpse into the prospects for gene therapy in liver disease – upon which we can count Jake to enlarge. So listen up!

Literature

• Arnson B et al. Efficacious genome editing in infant mice with glycogen storage disease type Ia. JCI Insight. 2025 Jul 31:e181760. doi:10.1172/jci.insight.181760. Online ahead of print. PMID: 40762955

• Tai CS et al. A prediction model for genetic cholestatic disease in infancy using the machine learning approach. J Pediatr Gastroenterol Nutr. 2025 Jul 30. doi:10.1002/jpn3.70166. Online ahead of print. PMID: 40735913

Dr Gottrand asks us to take on board that oesophageal atresia no longer is a disorder of infants only; presents us with the spectrum of evolution of oesophageal atresia in later childhood, adolescence, and adulthood, with its many and varied complications; and offers us recommendations for organisation of lifelong follow-up, with transition from paediatric to adult care. Two articles of relevance are cited below.

LiteratureKrishnan U et al. The International Network on Oesophageal Atresia (INoEA) consensus guidelines on the transition of patients with oesophageal atresia-tracheoesophageal fistula. Nat Rev Gastroenterol Hepatol 2023 Nov; 20(11):735-755. Doi: 10.1038/s41575-023-00789-w. Epub 2023 Jun 7. PMID: 37286639

Leroy M et al. Time to consider oesophageal atresia as a life-long disease. Int J Surg 2024 May 1; 110(5):2506-2507. Doi: 10.1097/JS9.0000000000001167. PMID: 38376869. PMCID: PMC11093440

Prof. Gottrand´s favourite song: Zaho de Sagazan - la symphonie des éclairs

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

She today is the guest of ESPGHAN at the hundredth podcast that your society has organised and sponsored. Think of it – one hundred podcasts! And that today she joins us is doubly a distinction, because her presidency of ESPGHAN was recently inaugurated in Helsinki: We here have the opportunity to meet her and to learn from her not only what ambitions and hopes she has for ESPGHAN but also how she has ascended the cursus honorum. In that ascent she has not simply balanced clinical care-giving with academic research; she has, by taking part in service to ESPGHAN and its members, helped to guide and to advance the society and its aims, which of course are listeners’ aims as well.

Listeners will not be surprised to learn that Prof Staiano is well-published, with contributions to many fields within paediatric gastroenterology, hepatology, and nutrition. At my request, she has named two works that are, in her opinion, of particular significance to her discipline... but also that are of particular significance to her. To review those works, and to hear her reflections on what they meant to her at the time of their accomplishment and in the years since, can illustrate the evolution of what has been a career of signal achievement, a career from which aspiring members, younger members, of ESPGHAN can surely learn.

Literature:

- Hyams JS et al. Childhood functional gastrointestinal disorders: Child / adolescent. Gastroenterology 2006 Apr;130(5):1527-1537. Doi: 10.1053/j.gastro.2005.08.063. PMID: 16678566. PMCID: PMC7104693Levine A et al. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014 Jun;58(6):795-806. Doi: 10.1097/MPG.0000000000000239. PMID: 24231644

Prof. Staiano´s favourite song: Torna a surriento” by Enrico Caruso

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

The hosepipes are trickling in the twilight, both at dawn and at dusk – but is it true that watering one’s garden in the heat of the day injures the plants? Wherever you are, dear reader and listener, let’s hope it’s somewhere shady, and that on the table next to where you’ve chosen to lounge and listen is a tall glass of something with ice cubes and gin. Lots of gin.

A tip of the hat to you who, under such adverse circumstances, have chosen to log in for the JPGN Journal Club! Our Teuton friends speak of Wissensdurstigkeit—thirst for knowledge. Today, let’s combine that with Gindurstigkeit—thirst for, well, you can read on.

Grab your highball and listen up, it’s Dr Jake Mann!

Jake’s choices for today:

First, from J Pediatr Gastroenterol Nutr, by Roilidis I et al., authors from a wide range of institutions:“Variability in the management of portal hypertension across European countries: A survey-study by the ESPGHAN Portal Hypertension Special Interest Group.”

Second, from Clin Gastroenterol Hepatol, a case report as a letter from Amsterdam, by de Boer ECW et al.:“A pedigree with complement hyperactivation, angiopathic thrombosis, and severe protein-losing enteropathy (CHAPLE) disease: Variable penetrance and treatment with pozelimab.”

The contribution from Roilidis et al. certainly underscores an unhappy truth: no one really knows the best way to manage patients with portal hypertension. Protocols that clearly demonstrate advantages in handling portal hypertension and its complications have yet to be defined, resulting in widely varying approaches. Pharmacotherapy with non-selective beta-blockers? Endoscopy with prophylactic intervention when varices are found? Meso-rex bypass construction? Transjugular intrahepatic portosystemic shunt placement? Treatment of hypotension-related sequelae during variceal hemorrhage? Roilidis et al. do not explain why different institutions choose different approaches. Perhaps the Special Interest Group will provide analysis, rather than description only, in follow-up work.

De Boer and colleagues evaluated a family from the Maghreb in which three siblings had digestive tract complaints. One brother was diagnosed with irritable bowel syndrome, and two sisters born eighteen years apart were diagnosed with Crohn disease, but not without some head-scratching. The older sister was initially diagnosed with anorexia nervosa before a more “organic” diagnosis was made. Whatever their condition, it did not respond to therapy that would usually control Crohn disease. Given the apparent familial incidence, genomic sequencing was undertaken. All three siblings were homozygous for a known disease-associated variant in CD55, which encodes a modulator of complement activation. Without such modulation, inflammation and thrombosis surge forward. Administration of an antibody targeting complement component C5 led to substantial clinical improvement in the two young women; the young man chose not to be treated.

A cautionary tale: don’t be Dr. Procrustes. When the patient doesn’t fit the diagnosis, when the guest doesn’t fit the furniture, step back and think again. Perhaps the guest would be better rested in a different bed, or the patient better treated in a different paradigm.

As a corollary question: should any patient labeled with treatment-refractory inflammatory bowel disease have their genome sequenced—before the appearance of similarly affected siblings, as in this family— as part of re-evaluation and second-line work-up?

Answers on a postcard, please, to the usual address.

Literaturede Boer ECW et al. A pedigree with complement hyperactivation, angiopathic thrombosis, and severe protein-losing enteropathy (CHAPLE) disease: Variable penetrance and treatment with pozelimab. Clin Gastroenterol Hepatol 2025 Jun; 23(7):1264-1267.e3. doi: 10.1016/j.cgh.2024.11.015. Epub 2024 Dec 15. PMID: 39689772

Roilidis I et al. Variability in the management of portal hypertension across European countries: A survey-study by ESPGHAN Portal Hypertension Special Interest Group. J Pediatr Gastroenterol Nutr 2025 Jun 12. doi: 10.1002/jpn3.70115. Online ahead of print. PMID: 40501451

Dr Scarallo – I’m tempted to call him simply “Luca,” as he was born in 1993, which makes him impossibly young – comes from Benevento, lying east and south of Naples. That city, his birthplace, has a history as impossibly long as Luca is impossibly young. It flourished under the Roman Republic and Empire, was the southern capital of the German Longbeards, the Longobardi, who ruled much of Italy fifteen hundred years ago, and belonged to the papacy for almost a millennium, till the creation of the Italian state in 1860.

Unimaginable for me, whose family and native country have practically no history at all…

At any rate, in flight from the weight of this enormous past, he went from the frying pan into two successive history-laden fires:

• To Milan for medical education, and

• To Florence for specialty training.

There, he now attends children with gastrointestinal disease, having spent a year away from Florence at the Hospital for Sick Children in Toronto—a refreshingly history-poor city—as an investigator.

Whilst his research interests centre on diet in inflammatory bowel disease, his chosen emphasis for this podcast interview is the use of sonography to assess the inflamed bowel – references to work in this area are supplied below.

As you listen, ask yourselves these questions, please:

• How do you use intestinal ultrasound in your daily practice?

• Has the introduction of intestinal ultrasound in investigation and diagnosis changed your practice?

• Can you imagine using intestinal ultrasound more extensively in the care of patients with inflammatory bowel diseases?

Literature

• Scarallo L et al. Bowel ultrasound scan predicts corticosteroid failure in children with acute severe colitis.J Pediatr Gastroenterol Nutr 2020 Jul; 71(1):46-51.Doi: 10.1097/MPG.0000000000002677. PMID: 32102087

• Kellar A et al. Intestinal ultrasound for the pediatric gastroenterologist: A guide for inflammatory bowel disease monitoring in children.Expert consensus on behalf of the International Bowel Ultrasound Group (IBUS) pediatric committee.J Pediatr Gastroenterol Nutr 2023 Feb 1; 76(2):142-148.Doi: 10.1097/MPG.0000000000003649. PMID: 36306530. PMCID: PMC9848217

• Chavannes M et al. Bedside intestinal ultrasound predicts disease severity and the disease distribution of pediatric patients with inflammatory bowel disease: A pilot cross-sectional study.Inflamm Bowel Dis 2024 Mar 1; 30(3):402-409.Doi: 10.1093/ibd/izad083. PMID: 37229656. PMCID: PMC10906360

  Dr. Scarallo´s favourite song: Caruso - Lucio Dalla

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

His first position as an attending physician began in 2009 at the Stollery Children’s Hospital in Edmonton, Alberta, where in 2021 he was appointed to a professorship of paediatrics at the University of Alberta – which he has just left to work again in Toronto at the Hospital for Sick Children.

His academic interests have centred on the interplay among diet, enteral microbiome, and intestinal inflammation.

When interviewed in Helsinki, at the 2025 annual meeting of ESPGHAN, he chose, however, rather than to concentrate on his contributions in this area, instead to address the important clinical question of:

• How to select initial therapy and

• How to progress to longer-term therapy in patients with inflammatory bowel disease, given the sometimes bewildering array of options in both testing and treatment.

He asks:

• What are the best treatments for paediatric inflammatory bowel disease in 2025, and how do we define "best"?

• How do we navigate a world with so many therapy options and choose the ‘best’ one for an individual patient?

• Finally, does the order matter in which we deploy the weapons in our armamentarium?

• Do we start with our most effective therapy or keep it for refractory cases only?

All this, with the ground beneath us continually quaking and shifting...

To specialise in the care of patients with inflammatory bowel disease requires substantial effort.With a guide like Dr Wine, however, one can be more confident that one is choosing well – as the references below demonstrate.

Literature

• Bressler B. Is there an optimal sequence of biologic therapies for inflammatory bowel disease? Therap Adv Gastroenterol 2023 Apr 5; 16:17562848231159452.Doi: 10.1177/17562848231159452. eCollection 2023. PMID: 37057077. PMCID: PMC10087655

• Spencer EA. Choosing the right therapy at the right time for pediatric inflammatory bowel disease: Does sequence matter. Gastroenterol Clin North Am 2023 Sep; 52(3):517-534.Doi: 10.1016/j.gtc.2023.05.006. PMID: 37543397

• Noor NM et al. Review article: Novel therapies in inflammatory bowel disease - An update for clinicians. Aliment Pharmacol Ther 2024 Nov; 60(9):1244-1260.Doi: 10.1111/apt.18294. PMID: 39403052

  Dr. Wine´s favourite song: Michael Jakson - We are the world

  ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

It’s JPGN Journal Club again with... wait for it... have you marked your score sheet, folded it in quarters, and dropped it into the sealed box? No? Too late now – because it’s Dr Jake Mann!

How many of you guessed right?

1. From J Pediatr Gastroenterol NutrStock et al. from Kassel, Germany – yes, the city of Documenta, Brothers Grimm, and once the capital of the Kingdom of Westphalia under Jérôme Bonaparte (who, by the way, emancipated the Jews and brought in the metric system – good job, Jerry!). This study comes from the Children’s Hospital there:

“Hydrostatic low-volume enemas in infants with birth weight ≤ 1000 g or gestational age ≤ 28 weeks: A controlled interventional study.”

What’s it all about? In short, they tested whether standardizing enemas in extremely premature infants could help improve outcomes like reducing NEC, intestinal perforation, or meconium plug syndrome. The answer: Yes, standardization helped – but didn’t change the need for parenteral feeding.The bigger question lingers though – does clearing meconium early really help overall? Probably not, say the authors. The gut’s still immature, no matter what you do. Or in Starfleet speak: Primum non nocere.

2. From Clin Gastroenterol HepatolBaccarella et al., at The Children’s Hospital of Philadelphia (CHOP – and side note, I grew up 50 km away, so Philly was once my Bright Lights, Big City).

“Outcomes of allogeneic hematopoietic stem cell transplant in monogenic inflammatory bowel disease.”

What they found will lift your spirits: In 25 kids (23 of whom had very early-onset IBD), stem cell transplants worked beautifully. No deaths. 23 are in remission and med-free up to 10 years later. Some bumps – infections, GVHD, veno-occlusive disease – but all manageable.Interesting detail: patients with certain genetic mutations (affecting both leukocytes and epithelial cells) didn’t respond as well as those with mutations limited to immune cells.

🎉 What good news! Brava la dottoressa Baccarella, bravi tutti i dottori di Filadelfia!

• Baccarella A et al. Outcomes of allogeneic hematopoietic stem cell transplant in monogenic inflammatory bowel disease. Clin Gastroenterol Hepatol. 2025 May 14:S1542-3565(25)00404-5.Doi: 10.1016/j.cgh.2025.03.018PMID: 40378986

• Stock T et al. Hydrostatic low-volume enemas in infants with birth weight ≤ 1000 g or gestational age ≤ 28 weeks: A controlled interventional study. J Pediatr Gastroenterol Nutr. 2025 May 8.Doi: 10.1002/jpn3.70055PMID: 40344423

Dr Giamouris has put his head over the parapet: not your usual interviewer, but instead Vangelis will shoot questions at Prof Assa; Prof Assa will shoot answers back; and the listeners can enjoy the firefight.

Vangelis, may the odds be ever in your favour!

Dr Giamouris was granted his medical degree at the University of Thessaly, trained in paediatrics in Athens at the Agia Sofia Children’s Hospital, and at present works at King’s College Hospital (London). He presents three clinical scenarios that involve aspects of paediatric ulcerative colitis to Prof Assa for his perspective on diagnosis and treatment.

Prof Assa is from Israel, where he trained. After a post-graduate fellowship in Toronto at the Hospital for Sick Children, he returned to Israel, where he chairs the Institute for Pediatric Gastroenterology at Kaplan Medical Center in Rehovot. He is also a full professor of pediatrics at Hebrew University in Jerusalem.

In his comments on Dr Giamouris’ clinical vignettes, he illustrates the principles set out in the recently updated ESPGHAN / NASPGHAN guidelines for physicians addressing paediatric ulcerative colitis — guidelines which are cited below.

Now let the games begin!

Literature – pending publicationManagement of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care — An Updated Evidence-based Consensus Guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organization

Management of Paediatric Ulcerative Colitis, Part 2: Acute Severe Colitis — An Updated Evidence-based Consensus Guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organization

Prof. Assa´s favourite song: James Taylor - Fire and Rain

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Sweden, though, is where Prof Olén is based, and where he mines clinical registries of children with inflammatory bowel disease to identify risks and risk factors for susceptibilities and complications. His particular interest is the question of whether or not the risk of cancer is increased in pediatric inflammatory bowel disease, and if so – what cancers, why, and to what extent, absolute and relative? Of course this raises an important corollary question: What are physicians and families to do with the estimates of risk that his work produces?

An introduction to that work is provided in the references below.

LiteratureOlén O et al. Childhood onset inflammatory bowel disease and risk of cancer: A Swedish nationwide cohort study 1964–2014. BMJ 2017 Sep 20; 358:j3951. Doi: 10.1136/bmj.j3951. PMID: 28931512. PMCID: PMC5605779

Everhov Å et al. Colorectal cancer in childhood-onset inflammatory bowel disease: A Scandinavian register-based cohort study, 1969–2017. J Pediatr Gastroenterol Nutr 2022 Oct 1; 75(4):480–484. Doi: 10.1097/MPG.0000000000003574. Epub 2022 Aug 18. PMID: 36125530

Olén O et al. Increasing risk of lymphoma over time in Crohn’s disease but not in ulcerative colitis: A Scandinavian cohort study. Clin Gastroenterol Hepatol 2023 Nov; 21(12):3132–3142. Doi: 10.1016/j.cgh.2023.04.001. Epub 2023 Apr 13. PMID: 37061104

Everhov Å et al. Cancer incidence in patients with ulcerative colitis naïve to or treated with thiopurine and targeted therapies – a cohort study 2007 to 2022 with comparison to the general population. J Crohns Colitis 2025 Jun 2:jjaf091. Doi: 10.1093/ecco-jcc/jjaf091. Online ahead of print. PMID: 40455688

Dr. Olen´s favourite song: Bara bada bastu” with KAJ.

ESPGHAN favourite Songs can be found on Spotify:https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

At JPGN Journal Club, with Dr. Jake Mann, reaching you today from ESPGHAN’s annual meeting, we uniformly are alert against diphyllobothriasis, Scourge of the North. Herring is on the menu this week—wish us luck.

Jake’s choices for today:

From J Pediatr Gastroenterol Nutr, by Kellar et al., writing from a number of North American institutions:“Defining normal bowel wall thickness in children with inflammatory bowel disease in deep remission: A multicenter study on behalf of the pediatric committee of the International Bowel Ultrasound Group (IBUS)”

From Hepatology, by Schwimmer et al., with investigators principally based in San Diego, CA:“Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study”

The JPGN article complements one recently discussed here at Journal Club. That article posed the question: Of what additional value is sonography in assessing extent of small-bowel involvement by inflammatory bowel disease at presentation?

The conclusion: not good enough to displace/replace other techniques, but it does pick up some disease that enteroscopy with biopsy and magnetic resonance imaging studies miss; particularly useful, perhaps, in patients who do not tolerate other techniques well.

The work by Kellar et al. is not the other half of a diptych; that is, it does not pose the question: Of what additional value is sonography in assessing extent of small-bowel involvement by inflammatory disease after clinically successful treatment? That work remains to be done.

A necessary lead-up to that work, however, is to determine by sonography how thick the wall of the bowel is—large and small—after inflammation has receded, with comparisons between regions assessed before as involved and regions assessed before as non-involved. The present study offers standard values likely to be useful in clinical practice.

Of course, aspects of study design permit quibbling—Jake holds both MD and MQ degrees, medicinae ac quibbolae doctissimus!—but overall, truly a pleasure to read and to think through.

Grappling with non-alcoholic fatty liver disease in children—or, more recently, metabolic dysfunction–associated steatotic liver disease (MASLD)—has never been easy. A child with abnormal clinical-laboratory test results that suggest hepatobiliary injury, obtained for no particular reason other than vigilance (as with required determinations of fitness to take part in sports), is referred for specialty evaluation.

Or—more often in the last several years—a fat child is defined prospectively as ill, is “medicalised”, and is referred for specialty evaluation. Colleagues in imaging-study departments say the liver is likely fatty. Oh. Well. Now what?

The natural history of MASLD seems to be largely undefined. So long as that is the case, to act is random—one needs a prognosis, the more detailed the better, to know what to watch out for, to understand how outcomes arise, and to consider intervention.

The authors write:

“The primary objectives of the study were to quantify the mortality rate and identify the causes of death in individuals with pediatric-onset MASLD. Secondary aims were to evaluate the incidence of cirrhosis and the development of extrahepatic outcomes including type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea.”

The authors followed for a mean of 8.5 years, 1,096 children aged 2–18 years who were diagnosed with MASLD between 2000 and 2017. Their findings demonstrate considerable hepatic morbidity and extrahepatic co-morbidity, with an increased death rate.

Whilst the population that they studied was 80% “Hispanic”, which precludes facile extrapolation of their conclusions to other ethnic groups—Mexican-American boys notoriously are butterballs, victims of the cultural conviction FOOD = LOVE—the authors’ findings will be, and perhaps should be, used to warrant screening and intervention (diet, exercise, GLP-1 receptor agonists), and thus are worth attention.

LiteratureKellar A et al. Defining normal bowel wall thickness in children with inflammatory bowel disease in deep remission: A multicenter study on behalf of the pediatric committee of the International Bowel Ultrasound Group (IBUS). J Pediatr Gastroenterol Nutr. 2025 Apr 29. doi: 10.1002/jpn3.70049. Online ahead of print. PMID: 40296563

Schwimmer JB et al. Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study. Hepatology. 2025 Apr 22. doi: 10.1097/HEP.0000000000001357. Online ahead of print. PMID: 40262118

This note accompanies a conversation recorded there with Dr. Roberto Canani, an expert in paediatric food allergy. In this podcast, however, he steps away from what might be considered the principal theme of his expertise—namely, immunologic dysregulation at the enteric mucosa and beyond.

Instead, he addresses three key questions:

1. What are ultraprocessed foods?

2. What evidence indicates that such foods facilitate the occurrence of paediatric gastrointestinal disorders?

3. What are the mechanisms of action by which such foods might contribute to paediatric gastrointestinal disease?

He refers to three relevant articles that help frame and answer these questions:

• Srour B et al. Ultra-processed foods and human health: From epidemiological evidence to mechanistic insights. Lancet Gastroenterol Hepatol. 2022 Dec; 7(12):1128–1140. doi: 10.1016/S2468-1253(22)00169-8. Epub 2022 Aug 8. PMID: 35952706

• Lane MM et al. Ultra-processed food exposure and adverse health outcomes: Umbrella review of epidemiological meta-analyses. BMJ. 2024 Feb 28; 384:e077310. doi: 10.1136/bmj-2023-077310. PMID: 38418082; PMCID: PMC10899807

• Canani RB et al. Ultra-processed foods, allergy outcomes and underlying mechanisms in children: An EAACI task force report. Pediatr Allergy Immunol. 2024 Sep; 35(9):e14231. doi: 10.1111/pai.14231. PMID: 39254357

Concern is growing about the effects of ultraprocessed foods on us all. Today, Dr. Canani helps us understand what is currently known and how to integrate that knowledge into clinical care.

Dr. Canani´s favourite song: Pavarotti - Nessun dorma 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Dr. Cernat has handpicked six interesting abstracts from this year’s ESPGHAN annual meeting to discuss with us (she found many more, of course, but podcast time constraints – you’ll understand). She explains why she chose these particular abstracts… though it’s entirely possible your assessments may differ. Judge for yourselves!

Abstracts (in order of discussion):

1. A cfCHIP-SEQ Liquid Biopsy for the Diagnosis of Autoimmune Hepatitis in Children

Publication: H-OP024 | Topic: AS02. Hepatology

This study explores the use of cfChIP-seq, a liquid biopsy technique, to diagnose autoimmune hepatitis (AIH) in children, offering a non-invasive alternative to liver biopsy. Researchers found distinct immune-related transcriptional activity in AIH patients, identifying a gene expression signature (“AIH score”) that distinguishes AIH from other liver diseases with 90% accuracy.

2. Gut Microbiota Response to Ileal Bile Acid Inhibitor Therapy in Children with Progressive Familial Intrahepatic Cholestasis

Publication: H-OP012 | Topic: AS02. Hepatology

Researchers evaluated how IBAT inhibitors and liver transplantation (LT) impact gut microbiota in PFIC patients. While LT restored microbiota function closer to normal, IBAT inhibitors did not significantly improve bile acid metabolism or microbiota composition—although changes were associated with clinical response in some cases.

3. A Set of Serum Proteomic Biomarkers Differentiates Celiac Children from Age and HLA-Matched Controls

Publication: G-OP010 | Topic: AS01. Gastroenterology

This study identified a panel of eight inflammation-related serum proteins that can differentiate children with celiac disease from HLA-matched healthy controls with over 90% accuracy. This holds promise for reducing the need for intestinal biopsy in diagnosis.

4. Long-Term Maintenance Treatment with Vedolizumab in Pediatric IBD: A Three-Year Follow-Up of the Prospective Multicenter VEDOKIDS Study

Publication: G-OP070 | Topic: AS01. Gastroenterology

A three-year prospective study found that vedolizumab is a safe and effective long-term maintenance therapy, particularly in pediatric UC (ulcerative colitis) patients. Early clinical remission (by week 6) was the best predictor of sustained remission over three years.

5. Mechanisms of Fetal Regulatory B Cell Induction by 2’-Fucosyllactose Supplementation During Pregnancy for Allergy Prevention

Publication: N-OP013 | Topic: AS03. Nutrition

This experimental study in mice suggests that prenatal supplementation with 2'-fucosyllactose (2’FL) enhances fetal immune tolerance by increasing B10 regulatory cells via maternal microchimerism. These findings may shed light on allergy prevention mechanisms starting in utero.

6. D-Lactate in Pediatric Patients on Enteral and Long-Term Parenteral Nutrition

Publication: N-OP033 | Topic: AS03. Nutrition

D-lactate levels were compared across pediatric patients receiving long-term parenteral nutrition, those post-intestinal adaptation, and healthy controls. Elevated D-lactate was linked to specific clinical settings like SBS, and genetic analysis was used to investigate possible metabolic contributors.

Elena´s song she brought from Finnland : Loituma - Ievan Polkka https://open.spotify.com/track/7aJMmhcw04NrO6whqwL23G?si=cc082143da8546bc

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

-- Are feeding difficulties adequately recognised and treated in children with food allergy ?

-- What is the context of the immune-supportive diet in addressing food allergy ?

-- What advances have been made around food allergy and tolerance induction ?

She offers us four articles to assist us in coming to grips with these issues.  A difficult field, and, one hopes, an interesting discussion.

Literature

Vlieg-Boerstra B et al.  The immune-supportive diet in allergy management :  A narrative review and proposal.  Allergy 2023 Jun 78(6):1441-1458.  DOI :  10.1111/all.15687.  Epub 2023 Apr 4.  PMID:  36802268

Meyer R et al.  World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update – VII – Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy.  World Allergy Organ J 2023 Jul 2416(7):100785.  DOI :  10.1016/j.waojou.2023.100785.  PMID :  37546235.  PMCID :  PMC10401347

Meyer R et al.  Diagnosis and management of food allergy-induced constipation in young children — an EAACI position paper.  Pediatr Allergy Immunol 2024 Jun35(6):e14163.  DOI :  10.1111/pai.14163. PMID :  38825829 

Chebar-Lozinsky A et al.  Assessing feeding difficulties in children presenting with non-IgE-mediated gastrointestinal food allergies—a commonly reported problem.  Nutrients 2024 May 2216(11):1563.  PMID :  38892497.  PMCID :  PMC11173616.    DOI :  10.3390/nu16111563 

Please visit https://www.espghan.org/knowledge-center to explore current offerings, and don't forget ESPGHAN’s annual meeting, taking place May 14–17 in Helsinki.

1.From Journal of Pediatric Gastroenterology and Nutrition (JPGN):Ritchie et al. (Aberdeen, UK, and Christchurch, NZ) –"Role of Noncontrast-Enhanced Abdominal Ultrasound in the Diagnostic Assessment of Pediatric Inflammatory Bowel Disease"

• A retrospective review of 47 children in New Zealand with inflammatory bowel disease (IBD).

• Examined the contributions of endoscopy, biopsy, magnetic resonance enterography (MRE), and noncontrast sonography (NCS) in diagnosing small-bowel involvement.

• Findings:

  • 14 children had no small-bowel disease.

  • Of the 33 with small-bowel involvement:

    • 19 had findings on NCS.

      • In 7 cases, NCS detected disease that endoscopy, biopsy, and MRE missed.

      • In 12 cases, NCS confirmed disease found by other modalities and found additional sites of involvement.

    • In 14 cases, NCS failed to detect small-bowel disease that other methods identified.

• Conclusion:NCS alone missed about two-fifths of cases but expanded diagnosis in about one-fifth.

2. From Nature:Rosenberger et al. (Czechia, Denmark, Germany) –"Deep Visual Proteomics Maps Proteotoxicity in a Genetic Liver Disease"

• Focused on alpha-1-antitrypsin storage disorder (A1ASD), where mutations in SERPINA1 cause alpha-1-antitrypsin (A1A) to accumulate in liver cells.

• Mechanisms of injury ("proteotoxicity") were unclear.

• The study used staining, microdissection, and mass spectrometry to analyze individual hepatocytes.

• Key findings:

  • Upregulation of the unfolded protein response.

  • Downregulation of hepatocellular synthesis and secretion processes.

  • Strong activation of peroxisomes in samples from individuals with less fibrosis; this activation declined in cases with more fibrosis.

• Implication:The authors speculate that peroxisome activators might help modulate disease progression.

• Limitations:The study focused on adult samples (ages 40–80), leaving unanswered how A1ASD leads to cholestasis in some infants but not others.

• Ritchie K, et al. Role of Noncontrast-Enhanced Abdominal Ultrasound in the Diagnostic Assessment of Pediatric Inflammatory Bowel Disease. JPGN, 2025 Apr 9.PMID: 40201985 | DOI: 10.1002/jpn3.70044

• Rosenberger FA, et al. Deep Visual Proteomics Maps Proteotoxicity in a Genetic Liver Disease. Nature, 2025 Apr 16.PMID: 40240610 | DOI: 10.1038/s41586-025-08885-4

• What is the prevalence of graft fibrosis in protocol biopsies in patients transplanted in childhood? How does fibrosis affect graft and patient survival?

• Should immunosuppressive therapy protocols be altered in liver-transplanted children?

• Are there alternative immunomodulatory concepts for children receiving a transplanted liver?

He offers three articles to assist us in coming to grips with these issues. Will his perspective resonate with yours?

Hartleif S et al. Outcomes of pediatric identical living-donor liver and hematopoietic stem cell transplantation. Pediatr Transplant 2016 Nov; 20(7):888-897. DOI: 10.1111/petr.12725. Epub 2016 May 30. PMID: 27241476

Hartleif S et al. Safety and tolerance of donor-derived mesenchymal stem cells in pediatric living-donor liver transplantation: The MYSTEP1 study. Stem Cells Int 2017; 2017:2352954. DOI: 10.1155/2017/2352954. Epub 2017 Jun 27. PMID: 28740511. PMCID: PMC5504958

Hartleif S et al. Long-term outcome of asymptomatic patients with graft fibrosis in protocol biopsies after pediatric liver transplantation. Transplantation 2023 Nov 1; 107(11):2394-2405. DOI: 10.1097/TP.0000000000004603. Epub 2023 Oct 21. PMID: 37143195

Dr. Hartleif favourite song: Komet -  Apache 207 and Udo Lindenberg https://open.spotify.com/track/7oQepKHmXDaPC3rgeLRvQu?si=48b00537429940bb

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Dr. Dragutinovic´s favourite song: Od kada tebe volim - Divana

ESPGHAN favourite Songs can be found on: https://open.spotify.com/track/13o1LAzN52dgTuemTFX6cE?si=d797b60e721a4032

The snowdrops are in their glory, the crocuses are a gaudy carpet, at least as this note is being compiled.

Little darling, it’s been a long, cold, lonely winter, but here comes – no, not the Sun, instead, JPGN Journal Club, led by Dr Jake Mann.

Please visit https://www.espghan.org/knowledge-center to examine the offerings, and don’t forget the Helsinki annual meeting, May 14-17, of ESPGHAN.

Your podcast team will be there. Stop by, please, with your thanks, congratulations, suggestions, and love-offerings centred on chocolate; meet us in person, say hello!

From J Pediatr Gastroenterol Nutr, by Iramain et al., writing from Hospital de Clínicas, Faculty of Medical Sciences, National University of Asunción, San Lorenzo, Paraguay:

“Lactobacillus reuteri Protectis DSM 17938 at high doses versus placebo in children with acute gastroenteritis in a Pediatric Emergency Department”

From Science, by Gracner et al., with co-authors at institutions in Canada, the USA, and Mexico – should I write “North USA, USA, and Mexico”? Or “North USA, USA, and South USA”? Or, which I’d prefer, “Canada, South Canada, and Mexico”? Everything is so fluid these days –

“Exposure to sugar rationing in the first 1000 days of life protected against chronic disease.”

The JPGN article reports a study of a commercial probiotic, BioGaia’s Protectis DSM 17938, which contains a patented strain of L. reuteri, in children aged less than 5 years who required emergent care for acute gastroenteritis and who were either mildly or moderately dehydrated. (The text hints that some children were admitted to hospital for care and that some were sent home, but provides no details.)

Two demographically similar cohorts were assembled, one given placebo (n=70) and one given Protectis (n=62). Over 5 days, numbers of stools daily fell more quickly among children given Protectis, whose disorder also resolved more quickly overall, than among children given placebo. The differences in favour of probiotic use reached statistical significance. The authors conclude that the BioGaia product can be useful in clinical settings.

The authors introduce their work with the claim:

“There are many adjuvants therapeutic strategies for treatment, including probiotics, however, their efficacy is still debated” (sic),

which might for some readers raise an eyebrow. L. reuteri has been studied forward and backward for more than thirty years, with documentation of efficacy and safety. Indeed, the BioGaia website (https://www.biogaiagroup.com/science/clinical-studies) states:

“To date, more than 260 clinical studies using BioGaia’s human strains of L. reuteri have been performed on approximately 22,000 individuals of all ages. Results have been published in more than 250 articles in scientific journals (Dec 2023).”

Might one wonder which deficiency in knowledge of L. reuteri this study has plugged?

In September 1953, sugar rationing ended in Britain. The article from Science describes differences in development of type 2 diabetes mellitus (T2DM) and hypertension between those who in utero were exposed to levels of sugar now recommended, that is, those born before rationing ended, and those born thereafter – when consumption of sugar nationwide doubled. (The authors took care to account for, and to exclude, contributions from shifts in dietary content of fat and of protein.)

To quote:

“The sample included 60,183 participants born between October 1951 and March 1956, aged 51 to 66 when surveyed. Adults conceived in the 1000 days before September 1953 were classified as “rationed” (born October 1951 to June 1954, n=38,155), and adults conceived after were classified as “never rationed” (born July 1954 to March 1956, n=22,028).”

And further:

“We found that early-life exposure to sugar rationing led to a reduction in T2DM and hypertension risk by about 35 and 20% and delayed the onset of these diseases by about 4 and 2 years, respectively.”

The longer the postnatal experience of sugar rationing, the more slowly these disorders developed. Sugar consumption variability did not seem to affect incidence of other disorders, helping to exclude non-specific effects.

Whilst data in UK Biobank, on which this study drew for subject recruitment, are generally derived from a relatively affluent tranche of Britishers, the authors claim that study design obviated concerns regarding applicability of any conclusions to broader segments of society.

Perhaps the principal audience for this work consists in obstetricians and perinatologists rather than in specialists in paediatric nutrition, in that in utero exposure to low-sugar diets was more protective than was postnatal exposure. However, since maternal consumption of sugar affects the exposure to sugar of the nursing infant, the work seems likely to be of interest to paediatricians in general.

Iramain R et al. Lactobacillus reuteri Protectis DSM 17938 at high doses versus placebo in children with acute gastroenteritis in a Pediatric Emergency Department. J Pediatr Gastroenterol Nutr 2025 Mar 3. PMID: 40026275 DOI: 10.1002/jpn3.70026 Online ahead of print

Gracner T et al. Exposure to sugar rationing in the first 1000 days of life protected against chronic disease. Science 2024 Nov 29;386(6725):1043-1048. PMID: 39480913 DOI: 10.1126/science.adn5421 Epub 2024 Oct 31

Literature :

Gutiérrez-Junquera C et al.  Proton pump inhibitor therapy in pediatric eosinophilic esophagitis:  Predictive factors and long-term step-down efficacy.  J Pediatr Gastroenterol Nutr 2023 Feb 1; 76(2):191-198.  doi: 10.1097/MPG.0000000000003660.  Epub 2022 Nov 23.  PMID:  36416845.  

Franciosi JP et al.  Medical treatment of eosinophilic esophagitis.  Cochrane Database Syst Rev 2023 Jul 20; 7(7):CD004065.  doi:  10.1002/14651858.CD004065.pub4.  PMID:  37470293.  PMCID:  PMC10358040.

Papadopoulou A et al.  Joint ESPGHAN / NASPGHAN guidelines on childhood eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis.  J Pediatr Gastroenterol Nutr 2024 Jan 78(1):122-152.  doi: 10.1097/MPG.0000000000003877.  Epub 2023 Jul 4.  PMID:  38291684.

Dr. Guiterrez favourite song: Hoy puede ser un gran día - Joan Manuel Serrat https://open.spotify.com/track/5YxgSArh0FDP0CEDuZcYnC?si=d70a2941550b48c9 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Ms Sigall-Boneh has contributed substantially to randomised clinical trials studying the effects of exclusionary diets, with partial enteral alimentation, in ameliorating clinical IBD.  Such diets can achieve patient-reported favourable results within three weeks of inception, matched by drops in faecal calprotectin values . . .  but they’re hard to adhere to.  Refining these diets has been her goal, that is, making adhesion practical.  The diets differ over time, with phases of inception, stabilisation, and retention, which in the last – she hopes – will be a boon conferred on the patient for life, as a result of training in how to eat better.  This approach has a rôle to play in combination with biologic / pharmacologic therapies, restoring a response to medication in treatment failure with anti-tumour necrosis factors (reduced inflammation, improved nutritional status with resolution of hypoalbuminaemia) and improving the degree of response in partial responders.  This can be tracked by microbiome status – microbiome composition shifts using the Crohn’s-disease diet, and shifts back again with re-introduction of “free diet” eating.  In short, a powerful set of arguments for closely involving dietary management in caring for IBD patients. 

Literature :

Levine A et al.  Crohn's disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial.  Gastroenterology 2019 Aug 157(2):440-450.e8.  doi: 10.1053/j.gastro.2019.04.021.  Epub 2019 Jun 4.  PMID :  31170412

Sigall Boneh R et al.  Clin Gastroenterol Hepatol 2021 Apr 19(4):752-759.  Dietary therapies induce rapid response and remission in pediatric patients with active Crohn's disease.  doi: 10.1016/j.cgh.2020.04.006.  Epub 2020 Apr 14.  PMID : 32302709  

Sigall Boneh R et al.  The Crohn's disease exclusion diet:  A comprehensive review of evidence, implementation strategies, practical guidance, and future directions.  Inflamm Bowel Dis 2023 Nov 18:izad255.  doi: 10.1093/ibd/izad255.  PMID : 37978895 

Dr. Sigall-Boneh´s favourite song: Hurricane - Eden Golan: https://open.spotify.com/track/2Ozw7k5CLtM5W9SomrOyjw?si=452d561a36e54f60

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Well, take heart: In the wonderland of JPGN Journal Club, led by Dr. Jake Mann, as the accompanying podcast is recorded, we’re deep into February. Listeners, keep on keeping on! Spring WILL arrive – just not soon enough.

Despite this horrid winter, ESPGHAN continues to work tirelessly for you. Visit https://www.espghan.org/knowledge-center – on III.05 there’s the GI Immunology Master Class: From pathogenesis to clinical management of EGID, coeliac disease, and IBD; on IV.02–04, there’s the Nutritional Assessment in Artificially Fed Children with Chronic Intestinal Disorders meeting; and, of course, the Helsinki annual meeting, V.14–17, is coming up. The calendar contains a clutch of further opportunities, beginning in early September. Not listed through ESPGHAN, but surely of interest to some in this podcast’s audience, will be the Congress on Pediatric Neurogastroenterology and Motility (Amsterdam, IX.11–13; www.pnm2025.nl).

Jake’s choices for discussion today: From J Pediatr Gastroenterol Nutr, by Mallhi et al., writing from five USA institutions, “The change of alanine aminotransferase distributions among US youths, NHANES 1988–2020”, and from Nat Commun, by Portlock et al., with co-authors at institutions that circle the globe, “Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition-related cognition.”

The JPGN article prompts two queries: What is NHANES? And why should one care about serum alanine aminotransferase (ALT) activity values (15,000 determinations) over 30 years in USA adolescents?

Easy answer first: NHANES is the National Health and Nutrition Examination Survey, which in USA residents collects demographic, socio-economic, dietary, and health-related data together with findings on physical examination and results of clinical-laboratory studies.

Tougher answer now: ALT values have been posited to track metabolic-dysfunction-associated steatotic liver disease (MASLD). Might population-wide ALT-value shifts allow assessment of effects of public-health interventions (reduction in consumption of ethanol/high-fructose sweeteners among adolescents)? Might they indicate sub-populations in whom further interventions are needed if MASLD incidence is to be reduced?

Using NHANES cohorts defined by age and by body-weight status (obese, overweight, normal, underweight), the authors identified across-the-board rises in ALT values when obesity increased among teenagers – and across-the-board falls in ALT values after access to ethanol and high-fructose sweeteners was restricted. Whilst ALT values fell overall, however, the incidence of MASLD did not. As always, then, more work is to be done if the burden of MASLD is to be reduced.

Malnutrition in childhood is, in survivors, associated with subnormal intelligence. What are the links between these two phenomena? The article from Nat Commun describes attempts to identify correlations among the enterobiome, stool composition, plasma lipid profiles, and evidence for impaired brain growth, development, and function, as assessed in two cohorts of Bangladeshi infants aged 11–13 months: 75 well-nourished (WN) and 159 with moderate acute malnutrition (MAM).

The enterobiome of infants with MAM was less diverse than that of WN infants, with an increased proportion of oral flora (although stool composition did not differ significantly between the cohorts). Among 792 plasma lipids assessed, differences between the cohorts were seen in 40 – some higher in MAM infants, some lower. Circulating odd-chain fatty acids and ceramides, in particular, were depleted in MAM.

Resting electroencephalography found decreased temporofrontal beta (12–30 Hz) and gamma (30–45 Hz) band activity, associated with concentration and alertness, in infants with MAM, who also, on behavioural assessment, lagged behind WN infants.

Network analyses found that Bacteroides fragilis abundance, in particular, was decreased in MAM. B. fragilis synthesizes several lipids important in nervous-system growth and development, and these lipids were depleted in MAM infants.

A mechanistic link remains to be tested in animal models, but the association is suggestive. Whether early intervention to prevent MAM – by provision of sufficient calories, perhaps – could generate changes in the enterobiome and, possibly in consequence, restoration of normal plasma lipid profiles, increases in electroencephalographic band activity, and regaining of age-appropriate neurodevelopmental milestones remains to be seen.

Literature

Mallhi AK et al. The change of alanine aminotransferase distributions among US youths, NHANES 1988–2020. J Pediatr Gastroenterol Nutr. 2025 Jan 13. PMID: 39803838 DOI: 10.1002/jpn3.12460

Portlock T et al. Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition-related cognition. Nat Commun. 2025 Jan; 816(1):473. PMID: 39773949 PMCID: PMC11707170 DOI: 10.1038/s41467-024-55798-3

1.   Which patients should be considered for endoscopic balloon dilatation of a Crohn's-disease stricture ?

2.   Who should perform the procedure ?

3.   Can dilatation of a stricture change the dynamics of regional inflammation ?

The last consideration is particularly interesting, I think . . .  but you, dear listeners, must be the judges of that.

Literature : 

Ledden O et al.  Approach to endoscopic balloon dilatation in pediatric stricturing Crohn disease:  A position paper of the endoscopy special interest group of ESPGHAN.  J Pediatr Gastroenterol Nutr 2023 Jun 1 76(6):799-806.  doi: 10.1097/MPG.0000000000003752.  Epub 2023 Mar 2.PMID: 36867853.

Dr. Ledders´s favourite song: 

https://open.spotify.com/track/7vmLO9qosfXIL9y4FTm588?si=775decc5a2d64fee

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

Kelly D et al.  Late graft hepatitis and fibrosis in pediatric liver allograft recipients:  Current concepts and future developments.    Liver Transpl 2016 Nov 22(11):1593-1602.  Doi:  10.1002/lt.24616.  PMID:  27543906.

Ruth N et al.  What is the long-term outlook for young people following liver transplant?  A single-centre retrospective analysis of physical and psychosocial outcomes.  Pediatr Transplant 2020 Nov 24(7):e13782.  Doi:  10.1111/petr.13782.  Epub 2020 Jul 17.  PMID:  32678500.

Wang HL.  Asymptomatic allograft fibrosis in pediatric liver transplantation:  Potential clinical implications.  Transplantation 2023 Nov 1 107(11):2314-2315.  Doi:  10.1097/TP.0000000000004604.  Epub:  2023 May 5.  PMID:   37143196.

Dr. Kelly´s favourite song: Danny Boy - Eva Cassidy https://open.spotify.com/track/0ZMdTY4ZBMyagiv9GBd06j?si=f8b52ee663b643f0 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

“Hark! It’s midnight, children dear. / Duck – here comes another year!”

In paraphrase, then, duck – here comes another instalment of JPGN Journal Club, led by Dr. Jake Mann! Before we move along to the articles to which Jake wants us to pay attention, have a glance at what ESPGHAN is doing for you at https://www.espghan.org/knowledge-center:

• 2025.I.30: Monothematic Conference on Steatotic Liver Disease in Children.
• III.05: GI Immunology Master Class: From Pathogenesis to Clinical Management of EGID, Coeliac Disease, and IBD.
• IV.02-04: A meeting on Nutritional Assessment in Artificially Fed Children with Chronic Intestinal Disorders.
• V.14-17: Don’t forget the Helsinki annual meeting!

Yes, the calendar is empty after that until early September, but then things get crowded. Sign up briskly, people, before the autumn’s offerings all are booked.

1. From J Pediatr Gastroenterol Nutr, by Anderson et al., writing from Helsinki and Stockholm:

   “Serum bile acids early after portoenterostomy are predictive for native liver survival and portal hypertension in biliary atresia.”

   The JPGN article provides evidence that, after hepatic portoenterostomy, monitoring serum bile-acid concentrations can supply prognostic information earlier and more sensitively regarding survival with the native liver or development of portal hypertension than monitoring serum bilirubin concentrations.

   As physicians, we take trouble with diagnosis to improve our performance with prognosis – our priestcraft in foretelling the future has earned our profession the high regard in which it is intermittently held. If this new-ish approach to prognostication can be confirmed as effective, we’ll all be using it, for our patients’ and their families’ sakes and for our own sakes as well.

2. From J Exp Med, by Ghasempour et al., writing from Paris, Rotterdam, and Toronto inter alia:

   “Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.”

   The article describing colitis associated with variants in the gene encoding integrin alpha-five (ITGAV) is almost as straightforward, once mystifying terminology is cleared away. Toward that end, a summing-up:

   • Integrins are heterodimer transmembrane proteins that mediate cell interactions with the extracellular matrix and with other cells.
   • Two integrins that include ITGAV, alpha-5-beta-6 and alpha-5-beta-8, activate transforming growth factor beta (TGF-β), which regulates aspects of chemotaxis and of cell proliferation, differentiation, and activation that modulate immune responses.

   The results of Ghasempour et al. seem to have started with genomic searches in several children with immunodeficiency, complex congenital malformations, and colitis, with one child requiring colectomy. The searches uncovered variants in ITGAV. Expression of ITGAV in cell lines from the children was substantially but not entirely ablated, leading to reduced nuclear accumulation of the promoter-region DNA-binding transcriptional regulator S-mothers against decapentaplegic homologue 3 – yes, this is the protein’s actual name! – that TGF-β activates.

   The cascade from upstream ITGAV expression to downstream disorders of the TGF-β pathway thus was documented. As it happens, variants in TGFB1, which encodes TGF-β, are found in children with faulty brain development and inflammatory bowel disease.

   As the cherry on top of this sundae, when the zebrafish orthologue of ITGAV was ablated, nervous-system defects and gut inflammation resulted.

   In short, then, another demonstration that TGFB1 and its targets are loci minoris resistentiae in at least some patients with inflammatory bowel disease. How long, then, before we shall clinically utilise TGF-β therapy in inflammatory bowel disease patients?

• Anderson L et al. Serum bile acids early after portoenterostomy are predictive for native liver survival and portal hypertension in biliary atresia. J Pediatr Gastroenterol Nutr 2024 Dec 31. DOI: 10.1002/jpn3.12451.
• Ghasempour S et al. Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis. J Exp Med 2024 Dec 2;221(12):e20240546. DOI: 10.1084/jem.20240546. Epub 2024 Nov 11. PMID: 39526957. PMCID: PMC11554753.

Literature :

J Pediatr Gastroenterol Nutr 2021 Sep 1 73(3):415-426.  doi: 10.1097/MPG.0000000000003207.  Homan M et al.  Percutaneous endoscopic gastrostomy in children:  An update to the ESPGHAN position paper.  PMID:  34155150.  

Tazi K et al.  Complications of percutaneous and surgical gastrostomy placements in children:  A single-centre series.  JPGN Rep 2023 May 9 4(2):e316.  doi: 10.1097/PG9.0000000000000316.  eCollection 2023 May.  PMID:  37200716.  PMCID:  PMC10187850.      

Dr. Bontem´s favourite song: To win the world - Peggy https://open.spotify.com/track/4B8x7E6BRMdXIw94w8PKwq?si=9a53caba74654bd3

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

Hyer W et al.  Management of familial adenomatous polyposis in children and adolescents:  Position paper from the ESPGHAN polyposis working group.  J Pediatr Gastroenterol Nutr 2019 Mar 68(3):428-441.  Doi:  10.1097/MPG.0000000000002247.  PMID:  30585891.

Latchford A et al.  Management of Peutz-Jeghers syndrome in children and adolescents:  A position paper from the ESPGHAN polyposis working group.  J Pediatr Gastroenterol Nutr 2019 Mar 68(3):442-452.  Doi:  10.1097/MPG.0000000000002248.  PMID:  30585892.  

Cohen S et al.  Management of juvenile polyposis syndrome in children and adolescents:  A position paper from the ESPGHAN polyposis working group.  J Pediatr Gastroenterol Nutr 2019 Mar 68(3):453-462.  Doi: 10.1097/MPG.0000000000002246.  PMID:  30585890.    

Dr. Hyer´s & Miss Cargill-Marin´s favourite song: Dancing Queen - ABBA https://open.spotify.com/track/0GjEhVFGZW8afUYGChu3Rr?si=bd491ca09a85451e

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Jake’s choices for discussion today: From J Pediatr Gastroenterol Nutr, by Fioretti et al., writing from Edinburgh, “A decade of real‐world clinical experience with 8‐week azithromycin–metronidazole combined therapy in paediatric Crohn's disease”, and from Pediatr Transpl, by Channaoui et al., writing from Brussels, “Failure to rescue pediatric recipients of living donor liver transplantation :  A single-center study of technical complications in 500 primary grafts”. The JPGN article addresses one of several options for initial remission induction in mild to moderately active Crohn’s disease. One choice is total parenteral alimentation ; another is corticosteroids ; and a third, that studied by Fioretti et al., is combined antibiotic treatment with azithromycin and metronidazole, which reportedly has been assessed in only twice before.  Among 44 children thus treated at Edinburgh, after 8 weeks 28 entered remission – 64%.  Among the 38 children who completed the treatment course (6 could not tolerate the treatment), again 28 entered remission – 74%.  The authors conclude that the combined therapy studied is an acceptable approach in at least some children with Crohn’s disease.  They do not, however, assess their experience with the other two approaches mentioned or cite the results of others’ work: How effective is total parental alimentation, how effective is corticosteroid treatment?  Without those data this article can not be optimally used in choosing among therapeutic options.

“Failure to rescue” is a recently introduced concept in assessment of quality of care. The Brussels group use it to mean “death of a complication of surgery”.  In severe liver disease, without liver transplantation all patients suffer from “failure to rescue”, and die ; liver transplantation is per se an attempt at rescue, and when a complication of that attempt supervenes, a complication that is not successfully treated and that ends in death, a “failure to rescue” has occurred.  Channaoui et al. examined rates of death and of graft loss at 1 and 5 years after living-donor liver transplantation in 500 children through the “failure-to-rescue” lens, tallying instances of arterial, venous, and biliary-tract complications and further tallying death and graft loss that could be ascribed to such complications.  Biliary-tract complications were most numerous, but arterial complications led to the most deaths and graft losses. A great deal of information is supplied on aetiologies of liver disease, age at liver transplantation, and surgical technique, but remarkably little is made of what the reader has ploughed through (or skimmed over) :  The authors do not speculate on how these factors contribute to “failure to rescue”.  Instead, they in conclusion offer rather general suggestions for avoiding arterial and venous complications, but not biliary-tract complications, and comment that “failure-to-rescue” analyses may hold promise for better clinical care.  Perhaps they may, but they may also simply be old wine in new bottles, mortality-and-morbidity reviews with a fashionable name.  

Literature

Fioretti MT et al.  A decade of real‐world clinical experience with 8‐week azithromycin–metronidazole combined therapy in paediatric Crohn's disease.  J Pediatr Gastroenterol Nutr 2024 Dec 9.  DOI :  10.1002/jpn3.12430.  PMID :  39648957

Channaoui A et al.  Failure to rescue pediatric recipients of living donor liver transplantation :  A single-center study of technical complications in 500 primary grafts.  Pediatr Transpl 2024 Nov; 28(7):e14861.

DOI :  10.1111/petr.14861.  PMID :  39320008  

Literature :

Moltu SJ et al.  Nutritional management of the critically ill neonate:  A position paper of the ESPGHAN committee on nutrition.  J Pediatr Gastroenterol Nutr 2021 Aug 1 73(2):274-289.  doi:  10.1097/MPG.0000000000003076.  PMID:  33605663

Dr. Moltu´s favourite song: Alle Snakker Sant - Siri Nilsen https://open.spotify.com/track/34gxnmqg4Nbzziv265qul7?si=4b3a424451c34844

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

Hansen BE et al.  Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.  Hepatology 2024 Jun 1 79(6):1279-1292.  doi:  10.1097/HEP.0000000000000727.  Epub 2023 Dec 25.  PMID:  38146932.  PMCID:  PMC11095900.

Dr. Kamath´s favourite song: At Last - Etta James https://open.spotify.com/track/4Hhv2vrOTy89HFRcjU3QOx?si=6f29d0369a3745c6 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Jake’s choices for discussion today :  From J Pediatr Gastroenterol Nutr, by Tessler et al., “The association of human milk intake and outcomes in biliary atresia”, and from Cell, by Jena et al., “Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair”.  We learn from the JPGN article that whilst high-energy formula feeding may be recommended in patients with extrahepatic biliary atresia, a diet that includes some human milk helps infants grow better than does one of formula alone, albeit without significant impact on a variety of other parameters.  From the Cell article we learn that in both radiation enteritis and inflammatory bowel disease, gut damage and repair alter DNA configuration to yield Z-nucleic acids, which in combination with Z-DNA binding protein (Z-DBP) activate caspase-8.  This then cleaves gasdermin C, which triggers inflammatory cell death, or pyroptosis (distinct from apoptosis, non-inflammatory cell death).  Type III interferon induces the up-regulation of Z-DBP, promoting pyroptosis.  Agents that modulate type III interferon expression or activity thus may lessen injury in inflammatory bowel disease.  

Literature

Tessler MEM et al.  The association of human milk intake and outcomes in biliary atresia.  J Pediatr Gastroenterol Nutr 2024 Nov 11.  DOI :  10.1002/jpn3.12403.  PMID :  39526563  

Jena KK et al.  Type III interferons induce pyroptosis in gut epithelial cells and impair mucosal repair.  Cell 2024 Oct 30 S0092-8674(24)01158-9.  DOI :  10.1016/j.cell.2024.10.010.  PMID :  39500322 

Literature :

Martino J et al.  Maternal body weight and gestational diabetes differentially influence placental and pregnancy outcomes.  J Clin Endocrinol Metab 2016 Jan 101(1):59-68.  doi:  10.1210/jc.2015-2590.  Epub 2015 Oct 29.  PMID:  26513002.  

Wahab RJ et al.  Associations of maternal early-pregnancy dietary glycemic index with childhood general abdominal and ectopic fat accumulation.  Clin Nutr 2021 Apr 40(4):1628-1636.  doi:  10.1016/j.clnu.2021.02.046.  Epub 2021 Mar 6.  PMID:  33752151.  PMCID:  PMC7613756.

Hull HR et al.  Growth and adiposity in newborns study (GAINS):  The influence of prenatal DHA supplementation protocol.  Contemp Clin Trials 2023 Sep 132:107279.  doi:  10.1016/j.cct.2023.107279.  Epub 2023 Jul 3.  PMID:  37406769.  PMCID:  PMC10852997.

Dr. Campoy´s favourite song: Taco's Rojas - Sebastian Yatra https://open.spotify.com/track/0Be7sopyKMv8Y8npsUkax2?si=981260cc5f6343cf

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

Zong W et al.  Blenderized enteral nutrition in pediatric short gut syndrome:  Tolerance and clinical outcomes.  Nutr Clin Pract 2022 Aug 37(4):913-920.  doi:  10.1002/ncp.10866.  Epub 2022 May 31.  PMID:  35638571.  PMCID:  PMC928327

Puoti MG, Köglmeier J.  Nutritional management of intestinal failure due to short bowel syndrome in children.  Nutrients 2022 Dec 23 15(1):62.  doi:  10.3390/nu15010062.  PMID:  36615720. PMCID:  PMC9823779.  

Dr. Dinning´s favourite song: Mull of Kintyre - Wings https://open.spotify.com/track/24RwOcKkC0hdiN1j3zjN1E?si=325b64a90d374745

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Jake’s choices for discussion today: From J Pediatr Gastroenterol Nutr, by Bouhuys et al., “Lateral flow test versus enzyme-linked immunosorbent assay to measure infliximab trough concentrations:  A head-to-head comparison” and from Nat Med, by Huang et al., “Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity”.  We learn from the JPGN article that lateral-flow testing results closely match those of the present standard of measurement – and are much more quickly obtained, perhaps permitting earlier intervention in an inflammatory-disease flare.  From the Nat Medarticle we learn that in obese children the lipidome is enriched in species associated with increased disease risk, an enrichment that can be reversed with non-pharmacologic intervention.  Such profiling may be useful in identifying risk and in tracking the efficacy of therapy.  

Literature

Bouhuys M et al.  Lateral flow test versus enzyme-linked immunosorbent assay to measure infliximab trough concentrations :  A head-to-head comparison.  J Pediatr Gastroenterol Nutr 2024 Oct 10.  DOI :  10.1002/jpn3.12372.  PMID :  39390697  

Huang Y et al.  Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity.  Nat Med 2024 Sep 20.  DOI : 10.1038/s41591-024-03279-x.  PMID : 39304782  

1) What is artificial intelligence and how can it be applied to paediatric gastroenterology, hepatology, and nutrition (PGHN) ?

2) What are disadvantages and risks associated with developing AI in medicine in general and in PGHN in particular ?

3) What do patients and families need to know about data security and AI ?

Dr de Laffolie presents a brief précis of how AI developed, pari passu with increased computational power, moving from “expert systems” with direct interrogation of a database through multilayered systems, in which filtration occurs in a database between question and answer in processes masked from the questioner, and onward to “deep learning” that integrates more than one database into the filtration.  AI already is used, he says, in surveillance endoscopy, improving (in adults) adenoma detection by a factor of 33%.  It also is of value in infectious-disease management, adult and paediatric alike, permitting those attending an infected patient to choose a treatment regimen on the basis of others’ concrete experience rather than that of theories.  But it must be used with care :  In hoping to profit by AI, patients or their parents confer on, confide in !, various databases information that might prove, somewhere down the road, even years later, disadvantageous to the propositus.  This possibility must be explained, with its long “lead time”, to the releasers of information to allow, to the extent that this is possible, informed consent.  Within these bounds AI can be, he believes, not a bad master that is held up for us to fear but instead a good servant.

Literature :

Schneider N et al.  Machine learning classification of inflammatory bowel disease in children based on a large real-world pediatric cohort CEDATA-GPGE^® Registry.  Front Med (Lausanne) 2021 May 24:8:666190.  doi: 10.3389/fmed.2021.666190.  eCollection 2021.  PMID: 34109197

Brooks-Warburton J et al.  Frontline Gastroenterol 2021 Dec 1013(4):325-331.  Artificial intelligence and inflammatory bowel disease:  Practicalities and future prospects.  doi: 10.1136/flgastro-2021-102003.  eCollection 2022.  PMID : 35722596

Stidham RW, Takenaka K.  Artificial intelligence for disease assessment in inflammatory bowel disease:  How will it change our practice?  Gastroenterology 2022 Apr 162(5):1493-1506.  doi: 10.1053/j.gastro.2021.12.238.  Epub 2022 Jan 4.  PMID :  34995537

Dr. DeLaffolie´s favourite song: Die perfekte Welle - Julie https://open.spotify.com/track/2LV5joNDrsyuXEh4FBARVK?si=d12211db83c74180 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

Marinschek S et al.  Long-term outcomes of an interdisciplinary tube weaning program:  A quantitative study.  J Pediatr Gastroenterol Nutr 2019 Apr 68(4):591-594.  Doi:  10.1097/MPG.0000000000002264.  PMID:  30633107.

Dr. Dunitz-Scheer´s favourite song: Ode an die Freude - Ludwig van Beethoven https://open.spotify.com/track/1aBkkvLvWRawhIj6qG93t0?si=070fb315a27045a4

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

For today’s discussion Jake has chosen a review of a small series of patients – from J Pediatr Gastroenterol Nutr, by D’Arienzo et al., “Characteristics and outcomes of home parenteral nutrition among children with severe neurological impairment” – and from Hepatology, by Xiao et al., a molecular-biologic analysis of cells that take part in the inflammatory, fibrotic, and proliferative processes of extrahepatic biliary atresia, “Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia”.  We learn from the JPGN article that severe neurological impairment confers neither benefit nor risk upon treatment with home parenteral nutrition, possibly a comforting conclusion.  From the Hepatology article we learn that blockade or knock-out of tumor necrosis factor receptor superfamily member 12A, or TNFRSF12A, ablates the usual changes in portal tracts of a mouse model of biliary atresia, suggesting an approach to therapy.  The techniques used in this study are complex – we’re lucky to have Jake as our guide to understanding it all.

Literature

D’Arienzo D et al.  Characteristics and outcomes of home parenteral nutrition among children with severe neurological impairment.  J Pediatr Gastroenterol Nutr 2024 Sep 10.  DOI :  10.1002/jpn3.12369.  PMID :  39252541 

Xiao MH et al.  Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia.  Hepatology 2024 Aug 23.  DOI :  10.1097/HEP.0000000000001064. PMID :  39178365 

Literature :

Waisbourd-Zinman O et al.  The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17. Hepatology 2016 Sep 64(3):880-893.  doi:  10.1002/hep.28599.  Epub 2016 May 20.  PMID:  27081925.  PMCID:  PMC4992464

Fried S et al.  Extrahepatic cholangiocyte obstruction is mediated by decreased glutathione Wnt and Notch signaling pathways in a toxic model of biliary atresia.  Sci Rep 2020 May 5 10(1):7599.  doi:  10.1038/s41598-020-645035.  PMID: 32371929.  PMCID:  PMC7200694.

Fried S et al.  Wnt and Hippo signaling pathways and microtubules:  Insights into biliary atresia mechanisms using a toxic model of the disease.  Pediatr Res, in press; 2024. 

 Dr Waisbourd-Zinman´s favourite song: Don't let the sun go down on me - Elton John https://open.spotify.com/track/11FcfHd3SOmmrWJPGe7Y30?si=96ee50d24ce243f3

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Literature :

van den Brink G et al.  Health care transition outcomes in inflammatory bowel disease:  A multinational Delphi study.  J Crohns Colitis 2019 Sep 19 13(9):1163-1172.  doi:  10.1093/ecco-jcc/jjz044.  PMID:  30766997.  PMCID:  PMC7142327.  

van Gaalen MAC et al.  Rotterdam transition test:  A valid tool for monitoring disease knowledge in adolescents with inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 2022 Jan 1 74(1):60-67.  doi:  10.1097/MPG.0000000000003278.  PMID:  34371508.

van Gaalen MAC et al.  Validation and reference scores of the transition readiness assessment questionnaire in adolescent and young adult IBD patients.  J Pediatr Gastroenterol Nutr 2023 Sep 1 77(3):381-388.  doi:  10.1097/MPG.0000000000003868.  Epub 2023 Jun 22.  PMID:  37347146.

Dr. Escher´s favourite song: Zeg maar niets meer - Andre Hazes https://open.spotify.com/track/2x7VFpoHN8eutpliLKFfuh?si=df044410412548dd

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

For today’s discussion Jake has chosen a case-review series of inflammatory bowel disease manifest after non-haematologic transplantation – from J Pediatr Gastroenterol Nutr, by Wenzel et al. – and from JHEP Reports, by Skarby et al., a long-term follow- up of children with autoimmune sclerosing cholangitis (AISC ; primary sclerosing cholangitis). The JPGN article describes eight children who several years after transplantation with various organs developed principally large-bowel inflammation with a lesser small-bowel component – neither ulcerative colitis nor Crohn disease, then – and speculates that tacrolimus in toddlers and small children may skew T-cell regulatory behaviour. On balance, the article is a “We saw this”, an exercise in bird- watching, and valuable as a guide to what are certainly rare birds.

Skarby et al. offer a similar stroll through the aviary, collecting 124 children and adolescents with AISC or with both autoimmune hepatitis and AISC – a very respectable number of instances of a disorder occurring in two per million – and following them for up to 21 years (median 13 [5.7–21.6] years). Long-term morbidity was low, which surprised the authors (91% transplant-free survival at 10 years). Even after discounting for shifts in care regimens over the study period, the data are a vade mecum for families affected by AISC and for their caregivers. How AISC differs from its adult counterpart remains to be investigated, and work like this sets parameters for the enquiries that must be undertaken.

Literature

Wenzel AA et al. Posttransplant inflammatory bowel disease after successful solid organ transplantation : Not out of the woods yet. J Pediatr Gastroenterol Nutr 2024 Aug 9. Doi : 10.1002/jpn3.12347. Online ahead of print. PMID : 39118496

Skarby AJ et al. Good long-term outcomes of primary sclerosing cholangitis in childhood. JHEP Rep 2024 May 25; 6(8):101123. Doi : 10.1016/j.jhepr.2024.101123. eCollection 2024 Aug. PMID : 39139456

Literature :

Lanigan JA et al.  Systematic review concerning the age of introduction of complementary foods to the healthy full-term infant.  Eur J Clin Nutr 2001 May 55(5):309-320.  doi:  10.1038/sj.ejcn.1601168.  PMID:  11378803.

Fewtrell M et al.  Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition.  J Pediatr Gastroenterol Nutr 2017 Jan 64(1):119-132.  doi:  10.1097/MPG.0000000000001454.  PMID:  28027215.

World Health Organisation.  WHO Guideline for complementary feeding of infants and young children 6-23 months of age.  Geneva:  World Health Organization 2023.  PMID:  37871145.

Dr. Laningan´s favourite song:  Teach Your Children - Crosby, Stills, Nash &  Young https://open.spotify.com/track/29HaKOpeLSYvqdFyEQSRdj?si=6815f57be2ce4bc0

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Literature :

Lambe C et al.  Long-term treatment with teduglutide:  A 48-week open-label single-center clinical trial in children with short bowel syndrome.  Am J Clin Nutr 2023 Jun 117(6):1152-1163.  doi: 10.1016/j.ajcnut.2023.02.019.  Epub 2023 May 3.  PMID:  37270289.

Norsa L et al.  Nutrition and intestinal rehabilitation of children with short bowel syndrome:  A position paper of the ESPGHAN committee on nutrition.  Part 1:  From intestinal resection to home discharge.  J Pediatr Gastroenterol Nutr 2023 Aug 177(2):281-297.  doi:  10.1097/MPG.0000000000003849.  Epub 2023 May 31.  PMID:  37256827.

Norsa L et al.  Nutrition and intestinal rehabilitation of children with short bowel syndrome:  A position paper of the ESPGHAN committee on nutrition.  Part 2:  Long-term follow-up on home parenteral nutrition.  J Pediatr Gastroenterol Nutr 2023 Aug 177(2):298-314.  doi:  10.1097/MPG.0000000000003850.  Epub 2023 May 31.  PMID:  37256821.

Germán-Díaz M et al.  Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate:  A multicenter study.  Eur J Pediatr 2024 Apr 26.  doi:  10.1007/s00431-024-05577-5.  Online ahead of print. PMID:   38664251.

Dr. Norsa´s favourite song: Piccolo Stella senza cielo - Ligabue https://open.spotify.com/track/0HpKuz1HfXxRzNnUqfwzgF?si=5de78bc63c994e5c

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Jake Mann has chosen for today’s discussion from J Pediatr Gastroenterol Nutr, by Granot et al., a case review of instances of autoimmune gastritis and from Hepatology, by Lefere et al., description and derivation of a proposed “scoring system” to predict fibrosis in non-referral-centre populations of fat children with abnormal serum transaminase activities, sonographic evidence of liver steatosis, and abnormal findings on elastography. The first raises the alarm for pernicious anaemia and gastric-mucosal malignant change in children with iron deficiency. The second hopes to streamline referral patterns for obese pediatric patients seen in the community. So, to quote Sondheim, slightly skewed : “What happens next ? That’s what’s in play / And you wouldn’t want us to give it away.” Have a listen !

Literature

Granot M et al. Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis. J Pediatr Gastroenterol Nutr 2024 Jul 16. Online ahead of print. Doi : 10.1002/jpn3.12318. PMID: 39010761.

Lefere S et al. Development and validation of pFIB scores for exclusion of significant liver fibrosis in pediatric MASLD. Hepatology 2024 Jul 19. Online ahead of print. Doi : 10.1097/HEP.0000000000001016. PMID : 39028885.

So, Dr Marra – an interventional radiologist, and like everyone across from whom I sit in these sessions, amazingly young to have accomplished so much.  He is an expert in how to deal with a not infrequent complication of premature birth – thrombosis of the external portal vein, a sequela of caregivers’ need for vascular access, via the umbilical vein, across the vena porta through the ductus venosus Arantii and into the vena cava.  With thrombosis comes portal hypertension, of course.  How to address portal hypertension of this aetiology – shunting, yes, but at what sites and how? – has for years been a concern of the liver team at Bergamo, Italy, where Dr Marra now works.  He believes that interventional-radiology approaches, rather than surgical ones, may be well-suited to certain patients.  

The Bergamo team argue for portal-vein recanalisation rather than transjugular intrahepatic portosystemic shunt (TIPS) placement, adducing these considerations: TIPS is poorly suited to the small and to the young, with substantial potential for injury during the procedure. A portosystemic shunt has its own adverse outcomes (nodular regenerative hyperplasia, even malignancy) -- why open a new shunt when we prefer to close them? TIPS placement can serve as a temporising measure until liver transplantation is feasible, but is not best for the long term.  The team also argue for percutaneous portal-vein recanalization when meso-Rex shunting is precluded; early results suggest that in half of such patients, patency can be restored, with good clinical outcomes. Longer-term follow-up is required, however, to assess prognosis and to permit proper counselling.

Literature :

Alberti D et al.  Results of a stepwise approach to extrahepatic portal vein obstruction in children.  2013 Nov 57(5):619-626.  doi:  10.1097/MPG.0b013e31829fad46.  PMID :  23783024  

Marra P et al.  The role of imaging in portal vein thrombosis:  From the diagnosis to the interventional radiological management.  Diagnostics (Basel) 2022 Oct 30 12(11):2628.  doi: 10.3390/diagnostics12112628.  PMID :  36359472, PMCID :  PMC9689990 

Deniz S et al.  Outcome of children with transjugular intrahepatic portosystemic shunt:  A meta-analysis of individual patient data.  Cardiovasc Intervent Radiol 2023 Sep 46(9):1203-1213.  doi: 10.1007/s00270-023-03520-z.  Epub 2023 Aug 2.  PMID : 37532945, PMCID :  PMC10471675

Dr. Marra´s favourite song: Con Le Mani - Zuccero https://open.spotify.com/track/6YyvSHhRZFaoE04mwkw5cY?si=13d7898e636442cc 

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo 

Literature :

Papadopoulou A et al.  Joint ESPGHAN / NASPGHAN guidelines on childhood eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis.  J Pediatr Gastroenterol Nutr 2024 Jan 78(1):122-152. doi:  10.1097/MPG.0000000000003877.  Epub 2023 Jul 4.  PMID: 38291684  

Low EE, Dellon ES.  Emerging insights into the epidemiology, pathophysiology, and diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases.  Aliment Pharmacol Ther 2024 Feb 59(3):322-340.  doi: 10.1111/apt.17845.  Epub 2023 Dec 22.  PMID:  38135920

Papadopoulou A, Zevit N.  Clinical presentation of patients with eosinophilic gastrointestinal diseases beyond eosinophilic esophagitis. Immunol Allergy Clin North Am  2024 May 44(2):349-355.  doi:  10.1016/j.iac.2024.01.006.  Epub 2024 Feb 13.  PMID: 38575228 

Dr. Papadopoulou´s favourite song: Gioconda´s Smile - Man's Hadjidakis https://open.spotify.com/track/1Y5Jr6NOKLLKLnxpJ0xi6a?si=c5bd157c5dc44ad7

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Dr Jake Mann has chosen for today’s discussion two heavy-hitting publications.  The first, from J Pediatr Gastroenterol Nutr, by Cohen et al., addresses the value of intestinal-rehabilitation treatment in congenital diarrhoea; the second, from J Hepatol, by Chichelnitskiy, Goldschmidt, et al., demonstrates that as the twig (of the biliary tree) is bent, so the hepatic forest is inclined:  That is, a seven-centre study found that prognosis for transplanted livers can be assessed by biomarker profiling in recipient plasma during the allograft’s first year.  

Both studies point the way toward the possibility of better clinical care.  A certain biomarker profile signalled longer-term success; can modulation of immunotherapy, or even choice of donor, shift a patient with a less advantageous profile toward an improved outcome, and can the shift be tracked using biomarker-value determinations?  Investigators worldwide are even now rummaging through their freezers, one imagines, for the banked samples to be used in confirming and extending these exciting results.  

Toronto, Cincinnati, and Haifa joined forces to assemble the cohorts of children whose longer-term courses they report.  Children with congenital diarrhoea, fifteen in all, did worse overall than did the “control” short-bowel syndrome (SBS) patients (1 : 3) with whom they were compared (59% vs. 87% and 39% vs. 80%, respectively, for 5- and 10-year survival rates).  However, they fared better than did historical congenital-diarrhoea controls, and in some respects they did as well as SBS patients.  Yes, we are making progress, it seems, regardless of how ward rounds leave us feeling from time to time.

Literature

Cohen IS et al.  Improved long-term outcome of children with congenital diarrhea followed by an intestinal rehabilitation program.  J Pediatr Gastroenterol Nutr 2024 Jun 3.  Online ahead of print.  Doi: 10.1002/jpn3.12275.  PMID:  38828718.

Chichelnitskiy E / Goldschmidt I et al.  Plasma immune signatures can predict rejection-free survival in the first year after pediatric liver transplantation.  J Hepatol 2024 May 29.  Online ahead of print.  Doi: 10.1016/j.jhep.2024.05.032.  PMID:  38821361.

Some patients, he says, respond to corticosteroids or to 5-acetylsalicylic acid alone; some with Crohn's disease must be advanced to tumour necrosis factor inhibitors such as infliximab or adalimumab, which are in efficacy much of a muchness ; some with ulcerative colitis respond better to infliximab than to adalimumab, meaning that to cover all bases in severe, undifferentiated disease, infliximab is the agent of choice.  Serum levels of drug and detection of anti-drug antibodies are important in titrating trough concentrations of small molecules, and in assessing “pharmacologic failure”, when initial measures are unsuccessful in stabilising and reducing disease.  Induction should be accompanied by therapeutic-drug monitoring, allowing modulation of treatment to reduce morbidity as early as possible. 

Additional agents, such as anti-integrin or anti-interferon antibodies are not approved for use in children, but they have their place in treatment failure.  The palette of those available is broad, and the names are complex and barbarous – listen with pencil and paper at hand, to take notes of what does what, and accept that your orthography will be approximate at best.  Re-assessment on endoscopy is often in order, with adjustment of therapy as additional (and more precise) data become available :  Switching based on histological activity alone is often partnered by a clinical setback, so be cautious in choosing criteria.  

Multiple-agent therapy and “extreme measures” ?  What does the gastroenterologist choose when his of her patient (and he or she) have their backs against the wall ?  Some situations, such as a stenosing and intractably inflamed bowel segment, require surgery initially.  Others call for drug combinations, watching out for excessive immunosuppression ; extraintestinal manifestations (perianal disease, cutaneous disease, cholangiopathy) must be borne in mind.  Surgery, however, can be a necessary fallback.  

Literature :

Conrad MA, Kelsen JR.  The treatment of pediatric inflammatory bowel disease with biologic therapies.  Curr Gastroenterol Rep 2020 Jun 15; 22(8):36.  doi:  10.1007/s11894-020-00773-3.  PMID:  32542562.   

Baumgart DC, Le Berre C.  Newer biologic and small-molecule therapies for inflammatory bowel disease.  N Engl J Med 2021 Sep 30; 385(14):1302-1315.  doi:  10.1056/NEJMra1907607.  PMID:  34587387

Grossberg LB et al.  Review article:  Emerging drug therapies in inflammatory bowel disease.  Aliment Pharmacol Ther 2022 Apr; 55(7):789-804.  doi:  10.1111/apt.16785.  Epub 2022 Feb 15.  PMID:  35166398 

Dr. Assa´s favourite song: מחכה - Idan Rafael Haviv https://open.spotify.com/track/3cmplhlwMZyQbuTHThyGe7?si=22085d464bb748d3

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

In speaking with Dr Bart Koot, of Amsterdam’s Emma Children’s Hospital and the University of Amsterdam Medical Centre, one might think “The diseases don’t change, just the names” – an adage once shared with me as I tried to make sense of some very muddy-seeming older publications.  “Non-alcoholic” and “fatty” are felt to be stigmatising nowadays, requiring a name-change or three ; instead of “fatty”, “steatotic liver disease” and “steatohepatitis” have been proposed, adopted, and recommended for use by persons prominent in hepatologic and hepatopathologic work.  What about “non-alcoholic” ?  Try “metabolic dysfunction-associated steatotic liver disease” (MASLD), subspeciated into instances with at least 1 of 5 cardiometabolic risk factors ; those with no disordered metabolic parameters and no known cause of steatosis now have “cryptogenic steatotic liver disease”.  And for those who don’t have pure metabolic dysfunction-associated steatotic liver disease, but instead take a drop now and again :  “MASLD alcohol-related / -associated liver disease overlap” (MetALD) is the term to use.  (“A drop”, 140–350g EtOH/wk and 210–420g EtOH/wk for females and males, respectively). 

This approach to usage will permit more precise understandings of what we talk about when we talk, or write, about steatotic liver disease, and that is salutary.  (How long these terms will not themselves be considered stigmatising is an open question.)  Whilst the terms have met with general acceptance in the northern hemisphere, of interest is that gastroenterologists in sub-Saharan Africa and in South America are not so enthusiastic – to be fat where most persons are chronically hungry is perhaps favourable, as a characteristic, rather than deprecatory.  Will the terms come eventually to be used worldwide ?  Time will tell.  

Specific aspects relevant to paediatricians are highlighted in the multisociety statement on paediatric steatotic liver disease, cited below.  Recommended ! 

Literature :

Younossi ZM et al.  Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.  J Hepatol 2024 Mar 80(3):419-430.  doi:  10.1016/j.jhep.2023.11.004.  Epub 2023 Nov 18.  PMID:  37984709

Rinella ME et al.  A multisociety Delphi consensus statement on new fatty liver disease nomenclature.  NAFLD Nomenclature consensus group.  Ann Hepatol 2024 Jan-Feb 29(1):101133.  doi:  10.1016/j.aohep.2023.101133.  Epub 2023 Jun 24.  PMID:  37364816

Baumann U et al.  Paediatric steatotic liver disease has unique characteristics:  A multisociety statement endorsing the new nomenclature.  J Pediatr Gastroenterol Nutr 2024 May 78(5):1190-1196.  doi:  10.1002/jpn3.12156.  Epub 2024 Mar 26.  PMID:  38529849

Dr. Koots favourite song: Kleine Jongen - Andre Hazes: https://open.spotify.com/track/0NMvLLGLKKJmSMqQSR38Sx?si=fe4165ebf12f4b84

ESPGHAN favourite Songs can be found on Spotify.

In the study from Rotterdam (Prof J Escher, team leader), proteomics screening identified several species more abundant in material from persons who had developed resistance to anti-tumour necrosis factor inhibition than in persons without such resistance.  The numbers of subjects in these two cohorts ?  Small.  The p value of the increases in abundance seen ?  Slight.  Larger numbers called for, perhaps with different statistical handling – but a promising start and an interesting attack on the question of “What leads to treatment failure ? “

Prof Kamath stepped forward to explicate the work by Islam et al. – quite properly, since it is her team’s work.  Extrahepatic bile-duct cholangiocytes, grown as organoids, were challenged with taurocholic acid and other agents, and the cholangiocytes’ responses, categorised by pathways of involved molecules, were charted and analysed.  Of interest was that a hitherto little-studied molecule, sphingosine-1-phosphate receptor 2, was implicated as participating strongly :  New routes for investigation !    

The information, viewpoints, and recommendations shared in this podcast are solely those of the hosts and guests, and may evolve over time as the field advances.

We hope you don’t leave, that is, switch off this podcast, although equally to please all 5300-plus delegate-guests at the ESPGHAN Annual Meeting Restaurant this year would be a miracle.  That’s 104 different countries-cuisines !  With courses in interventional ultrasound and in inflammatory bowel disease, also on offer are working-group and special-interest group meetings, an endoscopy learning zone, and an allied health professional course, together with 1433 accepted abstracts, uhm, menu items.  Now what about working a miracle? You ask.

Well, there’s riches there, something for everybody – has our chef assembled from among this a tasting menu for everybody ?  We think so.  She’s reviewed the entire bill of fare and has selected a double armful of dishes to set before you ; meaty, piquant, provocative, and in every instance driving forward the intellectual, clinically relevant, and tasty art of paediatric gastroenterology, hepatology, and nutrition.  Here’s your table! Loosen your clothing unobtrusively, say to Dr Elena Cernat of Leeds, chef extraordinaire – now what was that phrase ? Right! O-makase! – and get ready to feast.  

Elena Cernat´s favourite Italian song: Lasciate mi cantare https://open.spotify.com/track/5pzNrUTk5nhOOlUJQZGukp?si=e48dc20cde2743d3

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Dr. Vandenplas favourite song: Last Ons Ein Bloom https://open.spotify.com/track/2zcjUcLW0JaMCLEzkSWxke?si=d8340e40db4f4a9b

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Dr Jake Mann has chosen for today from Hepatology, by Stonebraker et al., Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis.  Genomes of substantial numbers of CFTR  disease patients, both with and without substantial liver disease (the former collected principally by centres in North Carolina and a centre In Ontario), were sieved for associations with the relatively uncommon but clinically burdensome features of biliary-tract injury and of malperfusional injury.  Indeed some were found, but what do they tell us about “novel mechanisms” ?  Hand-waving ensues.  A proof-of-concept study, then.  

Jake also has chosen, from J Pediatr Gastroenterol Nutr, by Di Lorenzo et al., Clinical trial :  Randomized controlled trial of linaclotide in children aged 6−17 years with functional constipation.  “News you can use”, perhaps:  Stooling improved to a respectable extent in those given higher doses of the agent, with the dosage ceiling still high above those employed so far. Response as a new discriminator, a new classifier, to permit dissection and separation of forms of functional constipation?  

Well, Jake as advocate will tell us what strengths and flaws he perceives in the two studies. Listen up, and don’t omit to pass the strawberries!

Dr. Vogel´s favourite song: Sgt. Peppers Lonely Heart Club https://open.spotify.com/track/4fUKE8EULjQdHF4zb0M8FO?si=df38f8c6709742df

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

As always, we’re glad to be back and we hope that you’re glad to have us back. Dr Jake Mann has chosen for today from Aliment Pharmacol Ther, by Ricciuto et al., Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD) :  A matched analysis from the Paediatric PSC Consortium.  And the consortium? Centres, 54 ; PSC patients, 1,362 ; PSC-IBD patients, 1061 ; PSC patients studied, 113. In matched cohorts, vancomycin recipients’ endoscopic and clinical-biochemistry indices of IBD improved substantially over control; no mention of how “liver numbers” responded. Fewer bacteria, less inflammation: Seems reasonable enough.  

Closer to ESPGHAN home is Jake’s next selection – from J Pediatr Gastroenterol Nutr – Lacaille et al., Awareness, referral and age at Kasai surgery for biliary atresia in Europe :  A survey of the Quality‐of‐Care Task Force of ESPGHAN.  Between 2015 and 2019, what referral patterns did 26 European hepatology centres see for 785 children with extrahepatic biliary atresia (EHBA)? Detection of jaundice by age 2wk to 3wk, with referral, is the goal – the reality, 55d (8wk ! ), hepatic portoenterostomy at age 61d, just past the 60d end of the period during which one can reasonably hope for good results.  Education campaigns thus far seem ineffective.  How to improve them? Also surveyed, 392 French paediatricians, a 20% response rate: Has introduction of stool-colour cards changed your handling of infantile cholestasis? Do you use the cards, do you feel that you understand cholestasis in infants? The faintly bilious answers, perhaps tinged with Gallic scepticism: Possibly ; Yes ; and . . . Frankly, no.  Too early to say if referral in France, and portoenterostomy results, will improve – card distribution, était-il battre l’eau avec un baton?

Prof. Scheer´s favourite song: Papaoutai - Stromae https://open.spotify.com/track/34dx8DACTJsc3rsJdaEIQw?si=5d88d0fe16a9437e

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Closer to ESPGHAN home is Jake’s next selection – from J Pediatr Gastroenterol Nutr – Raghu et al., Impact of early immunosuppression on pediatric liver transplant outcomes within 1 year. This collaborative effort among a double handful of North American centres permits a rather sad compare-and-contrast exercise with states of care in Scandinavia and in the USA (yes, one Canadian participant).  Medical provision on a scattershot, pick-and-mix basis is almost by whim in North America, it seems, whilst the Nordic lands offer co-ordinated, well-reasoned, and well-assessed interventions that enable supranational fine-tuning. One wonders what a similar look-back in Europe would discover, nation by nation and centre by centre, and what the discoveries would permit setting right.  Not that our bedside tables aren’t already stacked with enough to read, mind you, but at the top of that teetering pile should be the most recent number of JPGN.  Please grab it and read the Raghu et al. article. It’s a call to action.  May European hepatologists soon answer that call!

Dr. Thomassen favourite song: Har Du Fyr - Hekla Stalstrenga https://open.spotify.com/track/3Ks0fW1UMhfyiZJbweP4rW?si=01cdf4801c914b9c

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

A tip of the school cap to Molesworth, N., here – and as any paediatric hepatopathologist would predict, the Berlin- based consortium found that clinical parameters and values for various biomarkers, assessed in differing combinations, did not identify or correctly stratify liver fibrosis, and that the proper set of tests to use in non-invasive diagnosis of liver fibrosis still awaits definition in paediatric fatty liver disease. To be regretted – in this histopathologist’s opinion – is that the extent of fibrosis was not verified by a review team ; that is, the co-authors contributed not glass slides bearing tissue sections but copies of reports. Not the firmest of foundations, then . . . Well, however they got there, the conclusion of the study was prima facie correct : Keep those biopsy specimens coming !

The Coloradans and their co-workers report from Immunology World, in which evaluation of two brothers, born to first-cousin parents, for features of immunodeficiency found that they harboured a novel variant in LCK, encoding lymphocyte-specific protein tyrosine kinase (LCK). The effects of the variant included chronic diarrhoea ; histopathologic assessment of bowel mucosa is not reported. In knock-in mice with the same variant in Lck, however, chronic intestinal mucosal inflammation was present – not a feature in Lck knock-out mice. Immunophenotyping in the siblings and in the mice found selective deficiency in numbers of regulatory T-cells. The lads were successfully treated with bone-marrow transplantation. The mice could be successfully treated by topping up regulatory T-cells or by depleting CD4-expressing T-cells. Aside from the effects that the variant had on orderly development of T-cell subsets, the report interested Jake (and our listeners, we hope!) because of parallels that can be drawn with genetic contributions to chronic inflammatory intestinal disease. Patients like these have a lot to teach us, Jake maintains, as – like every British boy’s hero, “Biggles” – he returns safely to his home airfield, mission accomplished and Alex foiled.

As always, happy listening – and happy reading !

Dr. Kolho´s favourite song: Lintu - Suvi Teräsniska https://open.spotify.com/track/3Ks0fW1UMhfyiZJbweP4rW?si=1c2b39c5a1e44fc1

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

At the 2023 ESPGHAN annual meeting in Vienna he presented his experience with the forms of intrahepatic cholestasis encountered in patients with tight junction protein 2 disease, a disorder unfamiliar to many but of great interest in hepatic pathophysiology. He shares that experience with us now.

Dr. Sami´s favourite song: Helo - Adele https://open.spotify.com/track/1Yk0cQdMLx5RzzFTYwmuld?si=b4701baf63664ed8

ESPGHAN favourite Songs can be found on Spotify https://open.spotify.com/playlist/0YIHKjxITLEm9XNyHyypTo

Dr Özer Bekmez and her team compared the courses of pre-term infants who received magnesium sulfate (MgSO4) for neuroprotective purposes and pre-term infants who did not receive MgSO4. Findings included “a significant difference in intrauterine growth retardation (IUGR), preterm premature rupture of membranes, and the usage of antenatal steroids between the groups” – those receiving MgSO4 had worse IUGR, were more likely to have suffered from rupture of membranes, and were more likely to have been exposed to steroids ; they also went on to have more bronchopulmonary dysplasia and to require longer mechanical ventilation, with greater incidences of necrotising enterocolitis, feeding intolerance, and delay in enteral feeding. The authors posit these adverse outcomes as consequent on MgSO4 exposure. Were the dice loaded, though, given the more troubled antenatal course of those receiving MgSO4 ? Might MgSO4 administration have made no difference to outcome ?

The study design with Dr Bonilla and team was less questionable, perhaps. Although few patients were studied, when stool yielded enough microbial DNA for evaluation, results of next-generation sequencing correlated well with those of antibiotic sensitivity

testing in cultured gastric-biopsy material. Regrettable, though, that the authors made so little of potential benefits of speed – if DNA test results were in hand substantially before results of standard culture, selective antibiotic therapy might begin more quickly than possible at present, a boon to all.

Now for the letter pair, with Ms A Aloysius and colleagues writing in regard to the recent ESPGHAN Preterm Enteral Nutrition Position Paper (2022)—Issues of Oral Feeding on CPAP and Dr N Embleton offering a response on behalf of the position-paper authorial team. The initial letter says, in effect, “We as speech and language therapists believe that this position paper does not adequately address transition to oral feeding ! ” – the response says, “Erm, we rather think that we did, and here are the parts of our text in which we did, but whatever – yes, this is an important aspect of care, and one best approached in a multidisciplinary manner.” Fewer fireworks than in the best correspondential wars, and one must read the position paper to see if the speech and language therapists’ discipline truly was shortchanged.

As always, happy listening – and happy reading !

Prevalence and Risk Factors for Post-Discharge Feeding Problems in Children Born Extremely Preterm

Alm, Stina MSc^*; Stoltz Sjöström, Elisabeth PhD, RD^†; Domellöf, Magnus MD, PhD^*

LINK: https://journals.lww.com/jpgn/Fulltext/2023/04000/Prevalence_and_Risk_Factors_for_Post_Discharge.21.aspx 

The Yield of Routine Tissue Sampling in Pediatric Gastrointestinal Endoscopy

Anafy, Adi MD ^*,† ; Amir, Achiya Z.MD ^*,† ; Brazowski, Eli MD ^‡ ; Weintraub, Yael MD ^†,§ ; Yerushalmy Feler, Anat MD ^*,† ; Moran-Lev, Hadar MD ^*,† ; Dali Levy, Margalit RN ^* ; Ziv-Baran, Tomer PhD ^† ; Cohen, Shlomi MD ^*,† ; Ben-Tov, Amir MD ^*,†

LINK:  https://journals.lww.com/jpgn/Abstract/2023/04000/The_Yield_of_Routine_Tissue_Sampling_in_Pediatric.19.aspx

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Dr. Marco Gasparetto

ESPGHAN Podcast Host: Dr. Alex Knisely

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Dr. Lorenzo D´Antiga

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Dr Marianne Samyn

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Prof. Andreas Jenke

ESPGHAN Podcast Host: Dr. Alex Knisely

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Recording: Manuel Schuster