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.

JPGN Journal Club reports from the Milan venue of ESPGHAN’s 2024 annual meeting, seizing the opportunity to learn from those rarely in Europe – as today with Prof Binita Kamath, in transit between Toronto and Philadelphia professionally, who along with Dr Jake Mann will tag-team her way down the field shooting for goal with two articles of interest (Winter et al.’s Biomarkers predicting the effect of anti‐TNF treatment in paediatric and adult inflammatory bowel disease, from J Pediatr Gastroenterol Nutr 2024 May 2 doi: 10.1002/jpn3.12221, and Islam et al.’s A novel model to study mechanisms of cholestasis in human cholangiocytes reveals a role for the SIPR2 pathway, from Hepatol Commun 2024 Feb 268[3]:e0389).  

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

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

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

 

O-makase is the word of the day, the phrase that in Japan tells your chef that your meal is both literally and metaphorically in her hands – “Choose for me,” it means. Most fine dining has an equivalent; the French say menu de dégustation, here in Milan / Mailand / Milano it’s called menù degustazione. That is: Non prevede scelte da parte del cliente! You, the diner, have no say. Either eat what’s set on the plate in front of you or stand up and leave the restaurant. O-makase, baby !  

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

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

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

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