ESPGHAN Podcast

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