Three for two today ; one interviewer and two guests, Dr Warren Hyer and Ms Fiona Cargill-Marin in this ESPGHAN podcast, with its theme the management of polyposis syndromes in paediatric patients :  Not so much the from-what-age and the what-to-look-for as the origin of the guidelines first put forward by ESPGHAN going on five years ago and spearheaded by Dr Hyer, who is among the leaders of a well-coördinated effort to systematise relevant care, bringing it away from adult endoscopy services and into a paediatric model – family care rather than simply patient care, modulation through adolescence into adulthood, and the like.  Ms Cargill-Marin, as a paediatric nurse-practitioner in the clinic at St Mark’s Hospital (London) where Dr Hyer is active, offers her perspective on how such a multimodal clinic can function well.  

 

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

Happy holidays, everyone! 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 2025.I.15 the GI Winter School, on I.30 the Monothematic Conference on Steatotic Liver Disease in Children, and on III.05 the GI Immunology Master Class:  From pathogenesis to clinical management of EGID, coeliac disease, and IBD.

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  

 

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