ESPGHAN Podcast

The ESPGHAN podcast series today hopes to make you familiar with some of the work of Dr Sissel Moltu, a polyglot and polymath – she’s of Norwegian and USAnian heritage, was reared in Norway, took her medical degree in Freiburg, worked in England – who combined neonatology with gastroenterology when in Oslo University Hospital frustration at parenteral-alimentation – associated liver disease in short-bowel syndrome led her to make a career of investigating how best to feed the critically ill infant whilst sparing from injury the many growing systems, especially those of neurodevelopment (fatty-acid supplementation!).  She poses these questions for us: How does critical illness affect energy needs and the metabolic utilization of carbohydrates, protein, and fat? What is to be recommended in nutritional management of critically ill neonates (preterm and term infants)? Evidence for definitive recommendations in particular classes of newborns is still lacking. At any rate: If you can’t attend an ESPGHAN nutrition school, this podcast, and the “position paper” cited below, may at least give you a taste of what you’re missing. 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

Prof Dr Binita Kamath of first the United Kingdom (London’s King’s College Hospital), then the United States (Children’s Hospital of Philadelphia), then Toronto’s Hospital for Sick Children – and now, wait for it, the Children’s Hospital of Philadelphia again ! – speaks with us today in the ESPGHAN podcast series.  She has seen diagnosis of Alagille syndrome (AGS) move from clinicomorphologic assessment into two-pronged genetic sorting (first JAG1, then NOTCH2) and its treatment move from surgery (liver transplantation, biliary diversion) to pharmacology, with drug-based faecal wasting of bile salts via administration of the intestinal bile-salt uptake inhibitor maralixibat – those are her topics today, both the insights into maralixibat use gained from the Global Alagille Alliance group, or GALA, and the question :  “How did you achieve such a rocket of a career, and how would you advise young, ambitious paediatric hepatologists to make the most of their opportunities ? ”  She also touches on features of NOTCH2 disease, on the natural history of liver disease in AGS, and on evidence for thyroid dysfunction in AGS, together with forecasts for the evolution of therapy.  In passing, this note :  The report on maralixibat treatment cited below involves ninety-four co-authors – perhaps a record, at least in paediatric cholestatic liver disease !   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

December’s almost here, can you believe it ?  Here’s JPGN Journal Club, led by Dr Jake Mann !  Don’t forget ESPGHAN’s other educational offerings :  https://www.espghan.org/knowledge-center – on XII.27 the MOOC Enteral Nutrition in Preterm Infants conference, on 2025.I.01 the Young ESPGHAN Mentorship Programme, on I.15 the GI Winter School, and on I.30 the Monothematic Conference on Steatotic Liver Disease in Children.    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

The ESPGHAN podcast series today addresses three points that have defined the recent career of Dr Cristina Campoy Folgoso, professor and chair of paediatrics at the Medical University of Granada, Spain.  These ar : How maternal nutritional status can determine the offspring's growth and body composition during childhood ; which interventions during pregnancy may effectively prevent childhood obesity ; and which nutrients are most associated with the risk of childhood obesity.  Prof Campoy touches on timing of nutritional events during pregnancy, with the early observation that mothers starved in the last trimester have small babies excessively avid for nutriment, babies who over-produce adipocytes and develop metabolic disorders, an observation duplicated in animals.  Similarly over-avid babies are born overweight to obese or diabetic mothers, with similar predispositions to multi-organ dysfunction.  The placenta can compensate only so far for hyperalimentation owing to maternal overnutrition, it seems.  However, folic-acid and fatty-acid supplementation of the maternal diet may assist in dampening adipocytogenesis.  In addition, the newborn infant during its first year can reverse some of the changes induced by placental transfer of too many nutrients, although the reversal may take some time to become clinically evident.  Concerns that have arisen include transmission of the dysfunctional enterobiome from obese mother to the infant gut, with abnormal imprinting . . .  the effects go on and on, the echoes in systems seemingly remote from bowel and fatty tissue are becoming audible only now, and much exciting investigation is opening up. 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

Today’s ESPGHAN podcast series guest, Mrs Alison Dinning, is an academic dietitian at the Children’s Hospital of Bristol in the west of England.  Her interests centre on the care of children with short-bowel syndrome (SBS), with particular pleasure taken in successful shifts from parenteral to enteral alimentation – hard work, but if the family can be brought on board, then with use of breast milk, attention to what portions of the bowel are lacking, the use of blended (higher-density than simple liquid) feeds, and oral contact with food these children can be moved forward into enteral autonomy.  This in hospital ; but for discharge to home to succeed, the parents must be convinced by demonstration that they can and will succeed, and this requires in some instances instruction in how to prepare food, what to present to the child, to minimise food aversion and to allow family members and children alike to feel that they are taking part in the social event of eating.  Important strategies to support babies with SBS on the neonatal unit, then, and important strategies to improve enteral intake in children on home parenteral nutrition with SBS. 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

November:  Knocking on the door, or already inside and making itself at home ?  Whatever. It’s JPGN Journal Club, led by Dr Jake Mann! Don’t forget ESPGHAN’s other educational offerings:  https://www.espghan.org/knowledge-center – in particular on XI.11 the Winter School on Basic Science and Translational Research; on XI.15 a Masterclass on Transition from Paediatric to Adult Healthcare in Patients with GI or Liver Disease; and on XI.21 the 9th IBD Masterclass.   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

Today’s ESPGHAN podcast interviews Dr Jan de Laffolie, at present in Giessen (Germany), who has a strong interest in both inflammatory bowel disease and in “artificial intelligence”, or AI – that is, the sifting of data for correlations, not only those that are apparent to humans unassisted, call it to the naked eye / the naked mind, but also those that elude us mortals when we are on our own.  Working within a tripartite framework of :   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

Turmoil after Hitler’s war brought together the parents of today’s guest, Dr Marguerite Dunitz-Scheer ; she was born in the United States, reared in Switzerland, and with a marriage became Austrian.  She might have become a musician by profession – that was in her family’s blood, and she attended a conservatory as a teenager – but instead, true to the principle of everything, everywhere, and all at once that has informed so many of her life’s trajectories, she trained in medicine.  There, as a young mother herself, she was appalled to see how cruelly abused in the interests of “weight gain” small infants were, and how abnormally those infants responded to what should be a source of comfort, pleasure, delight :  Feeding, food, love.  Her analyses of video recordings of the gravely distorted interactions that she observed led her to develop programmes to restore more usual responses, allowing children’s innate drive toward learning and exploration to investigate food as fun, this whilst reducing the inhuman stress under which mothers suffered whose children had mis-learnt that to be fed was to be tortured :  “You must make sure that your baby eats” only turned the mothers into the torturers.  She has spent her career, then, in the behavioural paediatrics of feeding, based at the Medical University of Graz, in Austria, and today we are treated to an overview of that career -- her interest in the topic of tube feeding, the need for professionals to be involved in tube management and tube placement, and the many ways in which tube feeding affects child development, parents, and various social systems 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

October JPGN Journal Club, led by Dr Jake Mann !  As always, keep in mind ESPGHAN’s other educational offerings :  https://www.espghan.org/knowledge-center – in particular on X.25 a Monothematic Conference on Paediatric Gastric Disease ; on XI.11 the Winter School on Basic Science and Translational Research ; and on XI.15 a Masterclass on Transition from Paediatric to Adult Healthcare in Patients with GI or Liver Disease.  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

Interviewed today in the ESPGHAN podcast series is Dr Orit Waisbourd-Zinman, of Israel, who as a fellow in hepatology at the Children’s Hospital of Philadelphia was offered the chance to take part in studies of how “biliatresone”, a compound isolated from Australian plants (Dysphania sp.), might disrupt formation of extrahepatic biliary structures, as was postulated when sheep during drought ate unusual fodder, including Dysphania, and bore lambs that had biliary atresia.  Extrahepatic cholangiocytes of mice and zebrafish given biliatresone had abnormal primary cilia (a glance of interest toward “syndromic” biliary atresia, with abnormalities of situs generally associated with ciliopathy, is in order here) ; the biliary-atresia phenotype could be ameliorated by administration of glutathione.  Dr Waisbourd-Zinman has now returned to Israel, at the Schneider Children’s Medical Center, where she continues to investigate what the goddess Serendipity so generously cast into her lap.  She addresses for us her working hypotheses regarding biliary-atresia pathogenesis and aetiology, tells us what her laboratory studies concern (what models, what techniques), and forecasts for us what paths biliary-atresia research may take.   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

Dr Johanna (“Henkje”) Escher speaks with me for ESPGHAN’s podcast series today.  She works in learning how best to pass along the care of paediatric patients when, rather arbitrarily, they are declared to be adults.  All very well, no adolescent wants to be a child forever, but . . . well, paediatric disorders, that is, those that manifest themselves in early life, cover a far wider spectrum than do those that are unmasked only in adulthood, and to have been ill (and designated thus) for sixteen, eighteen, twenty-one years is, for a patient, baggage that “adult gastroenterologists” may not readily help carry.  I should not be surprised to learn that some “adult gastroenterologists” are afraid of, or at least nervous about, becoming primary caregivers for once-paediatric patients (and their parents) !  At any rate, Dr Escher shares with us today from Erasmus Medical Center / Sophia Children’s Hospital, Rotterdam, her insights and views on the complicated issue of transition in hepatogastroenterologic care, particularly in patients with inflammatory bowel disease, and with full involvement of the patients themselves (are they ready for agency ? ) :  What are the goals of transition ?  How is success to be defined ? What is the best way to conduct transitional care ?  Her experience is well worth taking on board for your practice.   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

JPGN Journal Club, led by Dr Jake Mann, is here again for August. As always, keep in mind ESPGHAN’s other educational offerings : https://www.espghan.org/knowledge-center – in particular on IX.12, AHP Summer School ; IX.21, the Young Investigator Forum ; IX.25, the 5th Liver Transplant School ; and X.25, a Monothematic Conference on Paediatric Gastric Disease. 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

Interviewed today in the ESPGHAN podcast series is Dr Julie Lanigan of University College London, working at several hospitals in London and lecturing in Plymouth, a dietitian whose interest is in complementary feeding (once called “weaning”, or the introduction of foods other than milk to an infant’s diet).  Not just foods, but feeding, taking part in the activities that define the family – gaining a seat at the breakfast, lunch, and dinner table – goes into complementary feeding :  Starting with new tastes, moving into new textures, and expanding beyond the sweet into the bitter or complex as the infant is socialised into a child.  Practices in the introduction of feeding differ among cultural groups, and public-health measures and tactics must take those differences into account.  Also to be considered are development of sensitivities and hypersensitivities, including life-threatening allergic reactions.  And all these concerns are thrown into relief when dealing with the infant in whom pre-term birth, long stays in hospital, and other problems interrupt the usual patterns of feeding and of its complementation.  Why, then, Dr Lanigan asks us, is complementary feeding a matter of concern and study ?  At what age should complementary feeding begin ?  What are the nutritional risks associated with inappropriate complementary feeding?  An interesting excursus through situations with which we may not involve ourselves so often as we should.  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

Bergamascheria ancora!  Yes, the Bergamo team have made available for a podcast yet another member, Dr Lorenzo Norsa, a professor of paediatrics there. Dr Norsa has been a fellow in paediatric gastroenterology in Israel and in France.  In Paris he became well-versed in treatment of short bowel syndrome, working with the prominent Necker team . . . perhaps their publications form a suite Bergamasque. (Apologies, M Debussy.) He speaks today on the use of teduglutide, an agent that mimicks the effects of the small-bowel enterocyte mitotic stimulant and anti-apoptotic life-prolonger glucagon-like peptide 2. Teduglutide increases the number of functional enterocytes, lengthening villi and deepening crypts, but does not go deeper, so to speak ; hyperplasia of the muscular coats and their elements is not induced, and the effects of teduglutide recede when the drug is withdrawn.  Perhaps this will not matter after puberty and its growth spurts are over, with less energy demand, but that remains to be seen.  A registry of patients is being compiled to permit better prognostication and more efficient dosage with what is a very expensive drug :  That early deployment of teduglutide improves overall results is known, but when to withdraw or how to modulate teduglutide administration are still open questions.   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

It’s JPGN Journal Club, led by Dr Jake Mann, in your electronic- device speakers, with the July podcast offering. Don’t forget to check out what ESPGHAN has available from July onward, here at https://www.espghan.org/knowledge-center -- in particular on IX.12, AHP Summer School, IX.21, the Young Investigator Forum, and on IX.25, the 5th Liver Transplant School. 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.

The ESPGHAN podcast guest today is Dr Paolo Marra – the interviewer, as our producer, Selma Ertl already has told you, is same old same old me – to round out the team, a hat-tip to Manuel Schuster, engineer. Let’s get starty with the party! 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

Interviewed today in the ESPGHAN podcast series is Hon. Prof. Dr. med. Alexandra Papadopoulou from Greece, Chair of the ESPGHAN Working Group and Special Interest Group on Eosinophilic Gastrointestinal Disorders for the last six years, Head of the Division of Gastroenterology, Hepatology and Nutrition of the First Department of Pediatrics of the National and Kapodistrian University of Athens and Head of the Department of Gastroenterology at the Athens Children's Hospital "Agia Sofia”. Among her interests is the entire spectrum of esophageal and extraesophageal diseases of the gastrointestinal tract characterized by eosinophilic leukocyte infiltration, tissue damage and dysfunction. Together with Professor Glenn Furuta from the University of Colorado, she coordinated the European and North American Societies of Pediatric Gastroenterology, Hepatology and Nutrition to issue a joint statement on eosinophilic disorders of the gastrointestinal tract beyond the esophagus – when to suspect them, how to diagnose them and what to do about them – and our chat today takes on this multifaceted topic. 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

JPGN Journal Club reporting for duty, sah! And mem! Here’s the spoken word about the written word . . . in a glorious June, with Heaven and Earth well and true in tune, as the poem goes.  Don’t forget to check out what ESPGHAN has on offer from July onward, available at https://www.espghan.org/knowledge-center ! 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.

ESPGHAN presents today an encounter with Prof Amit Assa, who like so many of those who have agreed to take part in these podcasts has filled all the posts of the medical-school and medical-administrative cursus honorum, steadily leaping upward from institution to institution.  As of now he is at the Institute of Paediatric Gastroenterology, Shaare Zedek Medical Centre, in Jerusalem, Israel (affiliated with Hebrew University) ; his interests are concentrated on inflammatory bowel disease.  Today he speaks about the modulation of small-molecule therapy, both increasing and decreasing, as disease is stabilized and wanes. 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

Today’s ESPGHAN podcast offers the opportunity to become acquainted with the effects of a revision in nomenclature.  Decades ago, stout – in both senses – Mormon matrons were vastly offended to learn that the form of steatohepatitis from which they suffered was histopathologically superimposeable upon that owing to ingestion of ethanol to excess ; the Word of Wisdom, a revelation vouchsafed in 1833 to Prophet Joseph Smith, expressly forbids ethanol to members of the Church of Jesus Christ of Latter-Day Saints, and the matrons swore up and down that they had forever been teetotal.  The term “non-alcoholic fatty liver disease” thus was born.   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.