ESPGHAN Podcast

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.