It’s ESPGHAN Journal Club, and—good heavens—it’s already November! Where did 2025 go? Lovely crisp sunny days, duvet-plus-blanket nights with very clingy cats, and foggy mornings with a fire in the woodstove to warm the kitchen and boil the kettle. After a nice cup of tea, let’s go shuffle-kick through the leaf piles with Dr. Jake Mann.

Jake’s choices for today: From J Pediatr Gastroenterol Nutr, by Anouti A. et al., writing from several USA institutions — Pediatric liver transplant outcomes: A comparative analysis of steatotic donor grafts. To follow, by Chu C. et al., from southern California under the palms of Los Angeles, and published in Hepatol Commun — Ultrasound of the rectus femoris as a novel tool to measure sarcopenia in pediatric chronic liver disease.

Be warned, prospective readers: although in neither selection do the authors squeeze cells and look at the juice — no pesky nucleic acids work! — you may want your hip boots: the statistics are scary deep.

Given that donor livers are growing fatter, the proportion of livers in which steatosis precludes use as an allograft may be increasing, Anouti et al. tell us. Adding to this, donor livers have never been abundant. The question posed: are outcomes substantially worse with fatty allografts than with lean allografts?

In the twenty years between 2004 and 2024, according to a USA liver transplantation database, 595 children and adolescents received liver allografts that were considered steatotic. In 62 (10.4%), steatosis affected >30% of parenchyma. Those recipients — in terms of one-year, five-year, and ten-year survival — fared no worse than did the other 533 with steatosis affecting <30% of parenchyma. This differs from what is observed in adults, who tolerate fatty implants poorly. In children, however, other factors conferred adverse prognosis. If those factors are borne in mind, and measures to address them are taken, the authors propose, fatty donor livers may be more widely usable.

Readers are not given several denominators: how many paediatric liver transplants took place overall? How many donor livers seemed dodgy enough to the surgical team that a histopathologist was called to evaluate a biopsy specimen? How many biopsied livers were discarded rather than implanted? And most importantly — what are survival rates in children who receive non-steatotic livers? To be regretted.

Chu and colleagues offer the results of imaging-study work intended to assess muscle bulk and consistency (fibrosis, fatty infiltration) in paediatric patients with chronic liver disease. Growth failure, they tell us, is not always reflected in paediatric end-stage liver disease scores that are used in selecting children for liver transplantation, and children not listed for transplantation but with growth failure not infrequently die while waiting for an organ.

Frailty and sarcopenia — lack of muscle mass — might, as indicators of growth failure, warrant consideration in juggling children up and down the transplantation list. What measurements, though, should one use in assessing muscle qualitatively and quantitatively? Where should measurements be taken?

Chu et al. subjected the rectus femoris, right and left, to ultrasonography, because that muscle is easy to find and easy to scan. They found that their measurements yielded internally and observer-to-observer consistent results, and that these results correlated well with clinical findings and clinical-laboratory biomarker values. Another arrow in the hepatologic quiver, then, and time will tell how often this new arrow is chosen to be nocked and shot — as well as how often, off the bowstring, it hits the intended target.

Two articles, two précis. But what does Jake think of these contributions to our literature? Why does he recommend that we grapple with them? Don’t click away — he’ll tell us.

Literature

Anouti A. et al. Pediatric liver transplant outcomes: A comparative analysis of steatotic donor grafts. J Pediatr Gastroenterol Nutr. 2025 Sep 22. DOI: 10.1002/jpn3.70213. Online ahead of print. PMID: 40977417

Chu C. et al. Ultrasound of the rectus femoris as a novel tool to measure sarcopenia in pediatric chronic liver disease.Hepatol Commun. 2025 Aug; 159(9): e0799. DOI: 10.1097/HC9.0000000000000799. PMID: 40824275. PMCID: PMC12363444

From Petah-Tikva, Israel – no map in your head? A tad east of Tel Aviv – at Schneider Children’s Medical Center, Dr. Anat Guz-Mark came to Helsinki for the ESPGHAN annual meeting, where this interview was recorded.

Her particular interest and expertise lie in intestinal failure and its therapies, with surgical short-bowel syndrome, paediatric intestinal pseudo-obstruction, and a variety of congenital enteropathies among the problems that she, her patients, and her patients’ families face together.

Listeners will learn her answers to five important questions:

1. What are the common causes for chronic intestinal failure in children other than surgical short-bowel syndrome?

2. What makes paediatric intestinal pseudo-obstruction or congenital enteropathies so challenging? Or, how do they differ from short-bowel syndrome?

3. Although life-saving for these patients, long-term parenteral nutrition comes with risks. What complications should clinicians anticipate?

4. What strategies are most effective in improving long-term outcomes?

5. What do we know about long-term outcomes and quality of life for these children?

She recommends the following articles for more comprehensive and detailed information than the interview could present.

Literature

• Duggan CP, Jaksic T. Pediatric intestinal failure. N Engl J Med 2017 Aug 17; 377(7):666–675. doi: 10.1056/NEJMra1602650. PMID: 28813225

• Lezo A et al. Chronic intestinal failure in children: An international multicenter cross-sectional survey. Nutrients2022 Apr 30; 14(9):1889. doi: 10.3390/nu14091889. PMID: 35565856. PMCID: PMC9103944

• 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.

• Demirok A et al. Pediatric chronic intestinal failure: Something moving? Nutrients 2024 Sep 3; 16(17):2966. doi: 10.3390/nu16172966. PMID: 39275281. PMCID: 11397488

Dr. Guz’s favourite song: Yuval Raphael – New Day Will Rise

ESPGHAN favourite Songs can be found on Spotify: Spotify Playlist

Joint work, or collective work, holds out substantial promise for advancing our understanding of how pathophysiology evolves over time and how best to alter the course of disease. ESPGHAN fosters such collaboration – the podcast that this note accompanies is a good example. A recently established registry of children with portal hypertension and its complications illustrates this effort.

In this episode, two physician-scientists who are among the registrars share their insights: Oanez Ackermann, of Le Kremlin–Bicêtre (Paris), and Tassos Grammatikopoulos, of King’s College Hospital (London). They address key questions:

• Why has a registry worthy of the name been so late in arriving?

• What are the registry’s goals?

• How can portal hypertension best be diagnosed non-invasively today, and what progress is expected in this area?

• How can pulmonary hypertension, a severe complication of portal hypertension, be best diagnosed?

Meaty stuff! For further details, you are referred to the articles listed below.

• El Koofy N et al. Prevalence and predictors of pulmonary hypertension in children with portal hypertension: A single center study. Pediatr Gastroenterol Hepatol Nutr. 2025 Mar; 28(2):101-112. Doi: 10.5223/pghn.2025.28.2.101. Epub 2025 Mar 5. PMID: 40109566. PMCID: PMC11919534

• Grammatikopoulos T et al. Considerations in the development of the International Multicenter Pediatric Portal Hypertension Registry. J Pediatr Gastroenterol Nutr. 2025 Jan; 80(1):197-202. Doi: 10.1002/jpn3.12415. Epub 2024 Nov 18. PMID: 39552494

• Rockey DC et al. Noninvasive liver disease assessment to identify portal hypertension: Systematic and narrative reviews supporting the AASLD Practice Guideline. Hepatology. 2025 Mar 1; 81(3):1086-1104. Doi: 10.1097/HEP.0000000000000841. Epub 2024 Mar 15. PMID: 38489516

Dr. Grammatikopoulos & Dr. Ackermann´s favourite song: Nina Simone – Feeling Good

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

It’s ESPGHAN Journal Club, in your thoughts and in your ears!

Thanks for tuning in to learn what Dr. Jake Mann thinks are the raisins in the loaf for this month.

Jake’s choices for today:

• Hoskins BJ et al. (Indianapolis, Indiana, USA), J Pediatr Gastroenterol Nutr – Pediatric endoscopic mucosal resection: A 10‐year single‐center experience.

• Kulecka M et al. (Cork and Galway, Ireland; Málaga, Spain; London; Utrecht), Nat Commun – Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis.

In what USAnians call “flyover country,” a ten-year review at a tertiary-care paediatric referral hospital included twenty mucosal or submucosal lesions treated by submucosal resection using cold- or hot-snare, banding, and underwater techniques. (Supplemental materials include videos of these resections.)

One lesion with fibrosis required surgical resection after endoscopic attempts. Otherwise, procedures were technically successful and well tolerated.

The authors have argued separately in J Pediatr Gastroenterol Nutr (link) for a discipline-wide reassessment of paediatric guidelines for endoscopic polypectomy. In their current report, they urge colleagues not to shy away from submucosal resection in children.

But questions remain: How should training be organized? How can enough cases be centralized so competence is maintained? Or, who will bell the cat? Problems for another day.

The authors frame their hypothesis clearly: not all children with ulcerative colitis (UC) respond to standard therapies. Could combined analysis of the mucosal microbiome, transcriptome, and epigenetic modifications predict which patients are at risk of relapse—allowing earlier use of second-line treatments?

Findings:

• Lower microbial diversity and depletion of butyrate-producing and mucin-degrading bacteria correlated with higher relapse risk.

• Colonisation of the distal bowel by oral flora—especially Veillonella dispar—marked a tendency for relapse. Similarly, V. parvula was overrepresented in relapsing patients.

• Functional studies in culture and mice showed pro-inflammatory effects not suppressed by standard UC therapies.

• Transcriptomic and epigenetic differences correlated with both microbiome composition and clinical course.

Conclusion: The authors propose that such analyses could identify children at higher risk of poor outcomes, emphasizing the novel predictive value of their approach. (Note: critical reading requires strong backgrounds in both statistics and microbiology—this is not light work!)

What do they signify for clinical practice and future research? Jake will tell us.

Departing from the bakeshop metaphor with which this commentary began, and paraphrasing from The Who’s rock opera Tommy:“With Jake as our leader, Jake as our guide / On the amazing journey together we’ll ride!”

Or, as Bette Davis (as Margo Channing in All About Eve) put it:“Fasten your seat belts – it’s going to be a bumpy night.”

Literature

• Hoskins BJ et al. Pediatric endoscopic mucosal resection: A 10‐year single‐center experience. J Pediatr Gastroenterol Nutr. 2025 Aug 12. Online ahead of print. doi:10.1002/jpn3.70194. PMID: 40798915

• Kulecka M et al. Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis. Nat Commun. 2025 Aug 4;16(1):7157. doi:10.1038/s41467-025-62533-z. PMID: 40759968. PMCID: PMC12322004

Prof. Dr. Nedim Hadžić – Dino attended the ESPGHAN annual meeting in Helsinki. Of course, your enterprising podcast team, lurking there to glean the thoughts and insights of the best and the brightest, snapped him up for an interview!

His training and early professional work were in Sarajevo, Bosnia-Herzegovina, but when he obtained a research fellowship in London, his supervisors soon recognised that he was too good to be allowed to return home.(For those who follow Croatian football: the centre-forward for Team Orijent in Sušak / Rijeka is a different Nedim Hadžić.)

Dino is now among the consultant hepatologists at King’s College Hospital, where he has cultivated an interest in alpha-1-antitrypsin storage disorder and circulating alpha-1-antitrypsin deficiency.(No, they’re not the same thing. We’ll blur the lines and henceforward refer to alpha-1-antitrypsin disease.)

He asks listeners today to think about:

• how alpha-1-antitrypsin disease may cause liver disease,

• how it may cause lung disease,

• why not all persons who harbour variants in SERPINA1 (which encodes alpha-1-antitrypsin) manifest clinical disease,

• and what can be done to treat severe liver disease associated with SERPINA1 variants.

He has provided a few references for us all, set out below.

Literature

• Francavilla R et al. Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. J Hepatol. 2000 Jun; 32(6):986-992. doi:10.1016/s0168-8278(00)80103-8. PMID: 10898319

• Hinds R et al. Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease. J Pediatr Gastroenterol Nutr. 2006 Jul; 43(1):136-138. doi:10.1097/01.mpg.0000226370.09085.39. PMID: 16819392

• Strnad P et al. Alpha1-antitrypsin deficiency. N Engl J Med. 2020 Apr 9; 382(15):1443-1455. doi:10.1056/NEJMra1910234. PMID: 32268028

• Clark VC et al. Fazirsiran for adults with alpha-1 antitrypsin deficiency liver disease: A phase 2 placebo-controlled trial (SEQUOIA). Gastroenterology. 2024 Oct; 167(5):1008-1018.e5. doi:10.1053/j.gastro.2024.06.028. Epub 2024 Jul 2. PMID: 38964420

  Dr. Hadzic´s favourite song: Indexi - Zute dunje

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

Inflammatory bowel disease: Important to assess, to treat, and to follow correctly, as Dr Anne-Marie Griffiths of Toronto confirmed in an interview recorded in Helsinki at the ESPGHAN annual meeting. She poses for us three questions:

1. What are some of the consequences for the patient when caregivers mislabel the type of inflammatory bowel disease?

2. What purpose is served by thorough diagnostic evaluation at presentation, with upper endoscopy, ileocolonoscopy, and small-bowel imaging?

3. What are the goals to be achieved by using the Paris classification or any of its future modifications?

This discussion addresses those questions, adducing the work in the references below and taking listeners through the evolution of categories of inflammatory bowel disease and their clinical associations.

LiteratureLevine A et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: The Paris classification. Inflamm Bowel Dis 2011 Jun; 17(6):1314-1321. Doi: 10.1002/ibd.21493. Epub 2010 Nov 8. PMID: 21560194

Levine A et al. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014 Jun; 58(6):795-806. Doi: 10.1097/MPG.0000000000000239. PMID: 24231644

Dhaliwal J et al. Phenotypic variation in paediatric inflammatory bowel disease by age: A multicentre prospective inception cohort study of the Canadian Children IBD Network. J Crohns Colitis 2020 May 21; 14(4):445-454. Doi: 10.1093/ecco-jcc/jjz106. PMID: 31136648. PMCID: PMC7242003

Ledder O et al. Appraisal of the PIBD-classes criteria: A multicentre validation. J Crohns Colitis 2020 Dec 2; 14(12):1672-1679. Doi: 10.1093/ecco-jcc/jjaa103. PMID: 32453831

Dr. Griffith´s favourite song: Allanis Morisette - Hand in my pocket

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

Welcome back to ESPGHAN Journal Club!

Give us your full attention, please – even if that means pulling into a lay-by or, even more demanding, setting down your drink. The thoughts and insights of Dr. Jake Mann are deffo worth the trouble.

Jake’s choices for today:

• From J Pediatr Gastroenterol Nutr, by Tai CS et al., with authors from Taiwan, Thailand, and Korea: “A prediction model for genetic cholestatic disease in infancy using the machine learning approach.”

• From JCI Insight, by Arnson B et al., with authors from the United States and the United Kingdom: “Efficacious genome editing in infant mice with glycogen storage disease type Ia.”

Machine learning, gene therapy… Journal Club is, as always, out in front – where Jake keeps dragging us.

The contribution from Tai et al. postulates that genetic analysis in neonatal cholestasis without mechanical obstruction is expensive and, in many sites, difficult to access. It advocates screening for genetic analysis and reports the retrospective sifting of 47 parameters per patient with intrahepatic neonatal cholestasis (1008 patients in total!), 63 of whom were ultimately diagnosed with “genetic cholestasis” (GC).

Among the 47 parameters assessed at presentation and again one month later, 20 – not including sonographic findings – proved useful in tracking GC. The predictive utility of this combination was checked in 36 patients with GC and 62 without, from two other institutions. Overall, about 70% of patients were identified as unlikely to have GC and might have been spared genetic analysis. The authors propose the algorithm, devised via machine learning, as a cost-saving measure.

What does Jake think of all this? Listen and find out.

Clinical caregivers and biomedical researchers at Duke University, North Carolina (USA), have made something of a hobby of glycogen storage disorders (GSDs) – their causes and cures – including glucose-6-phosphatase (G6P) deficiency (GSD1a). Adeno-associated virus has been used as a vector in mice, dogs, and humans to deliver functional G6PC copies (“transgenes”) into hepatocytes and renal tubular epithelium. These encode the catalytic subunit of G6P, variants of which cause GSD1a.

Unfortunately, G6PC transgenes introduced into hepatocytes are episomal, and episomal G6PC is rapidly lost in model mice and dogs – particularly in infant mice. Repeated or increased transfection does not adequately compensate for this loss.

The Duke Blue Devils (not “Dookies,” please – only Tar Heels use that term!) have now used CRISPR/Cas9-based techniques in 12-day-old G6pc-/- mice to achieve “long-term” genomic integration of G6PC, with euglycaemia sustained at least to age 12 weeks. (One supposes that counts as “long-term” in a mouse.)

The crucial question: will this prevent development of hepatocellular adenomas and carcinomas that occur in untreated humans and in episomally treated, but euglycaemic, mice and dogs?

As the ESPGHAN Journal Club mantra rises from the musical background: More studies are required. More FUNDING is required.

At any rate, this is an intriguing glimpse into the prospects for gene therapy in liver disease – upon which we can count Jake to enlarge. So listen up!

Literature

• Arnson B et al. Efficacious genome editing in infant mice with glycogen storage disease type Ia. JCI Insight. 2025 Jul 31:e181760. doi:10.1172/jci.insight.181760. Online ahead of print. PMID: 40762955

• Tai CS et al. A prediction model for genetic cholestatic disease in infancy using the machine learning approach. J Pediatr Gastroenterol Nutr. 2025 Jul 30. doi:10.1002/jpn3.70166. Online ahead of print. PMID: 40735913

Welcome to the world of oesophageal atresia and its treatment, where Prof Gottrand is eminent. (A quick hat-tip: His devotion to patient care was distinguished by the Premier prix mondial de l’atrésie de l’oesophage, awarded in June, 2019, at the World Congress on Oesophageal Atresia.) Surgical repair of oesophageal malformations yields palliation rather than cure, with a bewildering mix of dysmotility, dysphagia, malnutrition, reflux, inflammation, malignancy, and pulmonary and otolaryngologic disease all as sequelae; how are these patients, whether with a remodelled native oesophagus or a substituted organ, to be assessed and followed? Monstrously complicated! And improvement in survival means that year by year more and more patients with these problems must be attended and their problems addressed.

Dr Gottrand asks us to take on board that oesophageal atresia no longer is a disorder of infants only; presents us with the spectrum of evolution of oesophageal atresia in later childhood, adolescence, and adulthood, with its many and varied complications; and offers us recommendations for organisation of lifelong follow-up, with transition from paediatric to adult care. Two articles of relevance are cited below.

LiteratureKrishnan U et al. The International Network on Oesophageal Atresia (INoEA) consensus guidelines on the transition of patients with oesophageal atresia-tracheoesophageal fistula. Nat Rev Gastroenterol Hepatol 2023 Nov; 20(11):735-755. Doi: 10.1038/s41575-023-00789-w. Epub 2023 Jun 7. PMID: 37286639

Leroy M et al. Time to consider oesophageal atresia as a life-long disease. Int J Surg 2024 May 1; 110(5):2506-2507. Doi: 10.1097/JS9.0000000000001167. PMID: 38376869. PMCID: PMC11093440

Prof. Gottrand´s favourite song: Zaho de Sagazan - la symphonie des éclairs

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

La professoressa Annamaria Staiano è una figlia di Napoli, is a daughter of Naples, and to the city of her birth, medical education, and present professorial chair in paediatrics at the Università degli Studi di Napoli Federico II she has ever been loyal – aside from several years in St. Louis, Missouri, where she undertook subspecialty training in paediatric gastroenterology.

She today is the guest of ESPGHAN at the hundredth podcast that your society has organised and sponsored. Think of it – one hundred podcasts! And that today she joins us is doubly a distinction, because her presidency of ESPGHAN was recently inaugurated in Helsinki: We here have the opportunity to meet her and to learn from her not only what ambitions and hopes she has for ESPGHAN but also how she has ascended the cursus honorum. In that ascent she has not simply balanced clinical care-giving with academic research; she has, by taking part in service to ESPGHAN and its members, helped to guide and to advance the society and its aims, which of course are listeners’ aims as well.

Listeners will not be surprised to learn that Prof Staiano is well-published, with contributions to many fields within paediatric gastroenterology, hepatology, and nutrition. At my request, she has named two works that are, in her opinion, of particular significance to her discipline... but also that are of particular significance to her. To review those works, and to hear her reflections on what they meant to her at the time of their accomplishment and in the years since, can illustrate the evolution of what has been a career of signal achievement, a career from which aspiring members, younger members, of ESPGHAN can surely learn.

Literature:

- Hyams JS et al. Childhood functional gastrointestinal disorders: Child / adolescent. Gastroenterology 2006 Apr;130(5):1527-1537. Doi: 10.1053/j.gastro.2005.08.063. PMID: 16678566. PMCID: PMC7104693Levine A et al. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastroenterol Nutr 2014 Jun;58(6):795-806. Doi: 10.1097/MPG.0000000000000239. PMID: 24231644

Prof. Staiano´s favourite song: Torna a surriento” by Enrico Caruso

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

Summer! So hot... and everywhere is parched.

The hosepipes are trickling in the twilight, both at dawn and at dusk – but is it true that watering one’s garden in the heat of the day injures the plants? Wherever you are, dear reader and listener, let’s hope it’s somewhere shady, and that on the table next to where you’ve chosen to lounge and listen is a tall glass of something with ice cubes and gin. Lots of gin.

A tip of the hat to you who, under such adverse circumstances, have chosen to log in for the JPGN Journal Club! Our Teuton friends speak of Wissensdurstigkeit—thirst for knowledge. Today, let’s combine that with Gindurstigkeit—thirst for, well, you can read on.

Grab your highball and listen up, it’s Dr Jake Mann!

Jake’s choices for today:

First, from J Pediatr Gastroenterol Nutr, by Roilidis I et al., authors from a wide range of institutions:“Variability in the management of portal hypertension across European countries: A survey-study by the ESPGHAN Portal Hypertension Special Interest Group.”

Second, from Clin Gastroenterol Hepatol, a case report as a letter from Amsterdam, by de Boer ECW et al.:“A pedigree with complement hyperactivation, angiopathic thrombosis, and severe protein-losing enteropathy (CHAPLE) disease: Variable penetrance and treatment with pozelimab.”

The contribution from Roilidis et al. certainly underscores an unhappy truth: no one really knows the best way to manage patients with portal hypertension. Protocols that clearly demonstrate advantages in handling portal hypertension and its complications have yet to be defined, resulting in widely varying approaches. Pharmacotherapy with non-selective beta-blockers? Endoscopy with prophylactic intervention when varices are found? Meso-rex bypass construction? Transjugular intrahepatic portosystemic shunt placement? Treatment of hypotension-related sequelae during variceal hemorrhage? Roilidis et al. do not explain why different institutions choose different approaches. Perhaps the Special Interest Group will provide analysis, rather than description only, in follow-up work.

De Boer and colleagues evaluated a family from the Maghreb in which three siblings had digestive tract complaints. One brother was diagnosed with irritable bowel syndrome, and two sisters born eighteen years apart were diagnosed with Crohn disease, but not without some head-scratching. The older sister was initially diagnosed with anorexia nervosa before a more “organic” diagnosis was made. Whatever their condition, it did not respond to therapy that would usually control Crohn disease. Given the apparent familial incidence, genomic sequencing was undertaken. All three siblings were homozygous for a known disease-associated variant in CD55, which encodes a modulator of complement activation. Without such modulation, inflammation and thrombosis surge forward. Administration of an antibody targeting complement component C5 led to substantial clinical improvement in the two young women; the young man chose not to be treated.

A cautionary tale: don’t be Dr. Procrustes. When the patient doesn’t fit the diagnosis, when the guest doesn’t fit the furniture, step back and think again. Perhaps the guest would be better rested in a different bed, or the patient better treated in a different paradigm.

As a corollary question: should any patient labeled with treatment-refractory inflammatory bowel disease have their genome sequenced—before the appearance of similarly affected siblings, as in this family— as part of re-evaluation and second-line work-up?

Answers on a postcard, please, to the usual address.

Literaturede Boer ECW et al. A pedigree with complement hyperactivation, angiopathic thrombosis, and severe protein-losing enteropathy (CHAPLE) disease: Variable penetrance and treatment with pozelimab. Clin Gastroenterol Hepatol 2025 Jun; 23(7):1264-1267.e3. doi: 10.1016/j.cgh.2024.11.015. Epub 2024 Dec 15. PMID: 39689772

Roilidis I et al. Variability in the management of portal hypertension across European countries: A survey-study by ESPGHAN Portal Hypertension Special Interest Group. J Pediatr Gastroenterol Nutr 2025 Jun 12. doi: 10.1002/jpn3.70115. Online ahead of print. PMID: 40501451

Today’s guest is Dr Luca Scarallo, one of the rising stars in the constellation of experts in inflammatory bowel disease.

Dr Scarallo – I’m tempted to call him simply “Luca,” as he was born in 1993, which makes him impossibly young – comes from Benevento, lying east and south of Naples. That city, his birthplace, has a history as impossibly long as Luca is impossibly young. It flourished under the Roman Republic and Empire, was the southern capital of the German Longbeards, the Longobardi, who ruled much of Italy fifteen hundred years ago, and belonged to the papacy for almost a millennium, till the creation of the Italian state in 1860.

Unimaginable for me, whose family and native country have practically no history at all…

At any rate, in flight from the weight of this enormous past, he went from the frying pan into two successive history-laden fires:

• To Milan for medical education, and

• To Florence for specialty training.

There, he now attends children with gastrointestinal disease, having spent a year away from Florence at the Hospital for Sick Children in Toronto—a refreshingly history-poor city—as an investigator.

Whilst his research interests centre on diet in inflammatory bowel disease, his chosen emphasis for this podcast interview is the use of sonography to assess the inflamed bowel – references to work in this area are supplied below.

As you listen, ask yourselves these questions, please:

• How do you use intestinal ultrasound in your daily practice?

• Has the introduction of intestinal ultrasound in investigation and diagnosis changed your practice?

• Can you imagine using intestinal ultrasound more extensively in the care of patients with inflammatory bowel diseases?

Literature

• Scarallo L et al. Bowel ultrasound scan predicts corticosteroid failure in children with acute severe colitis.J Pediatr Gastroenterol Nutr 2020 Jul; 71(1):46-51.Doi: 10.1097/MPG.0000000000002677. PMID: 32102087

• Kellar A et al. Intestinal ultrasound for the pediatric gastroenterologist: A guide for inflammatory bowel disease monitoring in children.Expert consensus on behalf of the International Bowel Ultrasound Group (IBUS) pediatric committee.J Pediatr Gastroenterol Nutr 2023 Feb 1; 76(2):142-148.Doi: 10.1097/MPG.0000000000003649. PMID: 36306530. PMCID: PMC9848217

• Chavannes M et al. Bedside intestinal ultrasound predicts disease severity and the disease distribution of pediatric patients with inflammatory bowel disease: A pilot cross-sectional study.Inflamm Bowel Dis 2024 Mar 1; 30(3):402-409.Doi: 10.1093/ibd/izad083. PMID: 37229656. PMCID: PMC10906360

  Dr. Scarallo´s favourite song: Caruso - Lucio Dalla

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

Dr Eytan Wine was graduated from the School of Medicine at Tel Aviv University in 1998, with training in paediatrics at Wolfson Medical Center in Holon, Israel, followed by specialty training in gastroenterology, hepatology, and nutrition at the Hospital for Sick Children in Toronto, where he also earned a PhD degree for studies in bacterially induced intestinal inflammation.

His first position as an attending physician began in 2009 at the Stollery Children’s Hospital in Edmonton, Alberta, where in 2021 he was appointed to a professorship of paediatrics at the University of Alberta – which he has just left to work again in Toronto at the Hospital for Sick Children.

His academic interests have centred on the interplay among diet, enteral microbiome, and intestinal inflammation.

When interviewed in Helsinki, at the 2025 annual meeting of ESPGHAN, he chose, however, rather than to concentrate on his contributions in this area, instead to address the important clinical question of:

• How to select initial therapy and

• How to progress to longer-term therapy in patients with inflammatory bowel disease, given the sometimes bewildering array of options in both testing and treatment.

He asks:

• What are the best treatments for paediatric inflammatory bowel disease in 2025, and how do we define "best"?

• How do we navigate a world with so many therapy options and choose the ‘best’ one for an individual patient?

• Finally, does the order matter in which we deploy the weapons in our armamentarium?

• Do we start with our most effective therapy or keep it for refractory cases only?

All this, with the ground beneath us continually quaking and shifting...

To specialise in the care of patients with inflammatory bowel disease requires substantial effort.With a guide like Dr Wine, however, one can be more confident that one is choosing well – as the references below demonstrate.

Literature

• Bressler B. Is there an optimal sequence of biologic therapies for inflammatory bowel disease? Therap Adv Gastroenterol 2023 Apr 5; 16:17562848231159452.Doi: 10.1177/17562848231159452. eCollection 2023. PMID: 37057077. PMCID: PMC10087655

• Spencer EA. Choosing the right therapy at the right time for pediatric inflammatory bowel disease: Does sequence matter. Gastroenterol Clin North Am 2023 Sep; 52(3):517-534.Doi: 10.1016/j.gtc.2023.05.006. PMID: 37543397

• Noor NM et al. Review article: Novel therapies in inflammatory bowel disease - An update for clinicians. Aliment Pharmacol Ther 2024 Nov; 60(9):1244-1260.Doi: 10.1111/apt.18294. PMID: 39403052

  Dr. Wine´s favourite song: Michael Jakson - We are the world

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

You’ll never guess who’s across the table from me today – well, across the miles, since we’re encountering one another via ZOOM, but either way, you’ll never guess.

It’s JPGN Journal Club again with... wait for it... have you marked your score sheet, folded it in quarters, and dropped it into the sealed box? No? Too late now – because it’s Dr Jake Mann!

How many of you guessed right?

1. From J Pediatr Gastroenterol NutrStock et al. from Kassel, Germany – yes, the city of Documenta, Brothers Grimm, and once the capital of the Kingdom of Westphalia under Jérôme Bonaparte (who, by the way, emancipated the Jews and brought in the metric system – good job, Jerry!). This study comes from the Children’s Hospital there:

“Hydrostatic low-volume enemas in infants with birth weight ≤ 1000 g or gestational age ≤ 28 weeks: A controlled interventional study.”

What’s it all about? In short, they tested whether standardizing enemas in extremely premature infants could help improve outcomes like reducing NEC, intestinal perforation, or meconium plug syndrome. The answer: Yes, standardization helped – but didn’t change the need for parenteral feeding.The bigger question lingers though – does clearing meconium early really help overall? Probably not, say the authors. The gut’s still immature, no matter what you do. Or in Starfleet speak: Primum non nocere.

2. From Clin Gastroenterol HepatolBaccarella et al., at The Children’s Hospital of Philadelphia (CHOP – and side note, I grew up 50 km away, so Philly was once my Bright Lights, Big City).

“Outcomes of allogeneic hematopoietic stem cell transplant in monogenic inflammatory bowel disease.”

What they found will lift your spirits: In 25 kids (23 of whom had very early-onset IBD), stem cell transplants worked beautifully. No deaths. 23 are in remission and med-free up to 10 years later. Some bumps – infections, GVHD, veno-occlusive disease – but all manageable.Interesting detail: patients with certain genetic mutations (affecting both leukocytes and epithelial cells) didn’t respond as well as those with mutations limited to immune cells.

🎉 What good news! Brava la dottoressa Baccarella, bravi tutti i dottori di Filadelfia!

• Baccarella A et al. Outcomes of allogeneic hematopoietic stem cell transplant in monogenic inflammatory bowel disease. Clin Gastroenterol Hepatol. 2025 May 14:S1542-3565(25)00404-5.Doi: 10.1016/j.cgh.2025.03.018PMID: 40378986

• Stock T et al. Hydrostatic low-volume enemas in infants with birth weight ≤ 1000 g or gestational age ≤ 28 weeks: A controlled interventional study. J Pediatr Gastroenterol Nutr. 2025 May 8.Doi: 10.1002/jpn3.70055PMID: 40344423

Today’s podcast is a change of pace.It showcases not only Prof Dr Amit Assa, offering his expertise in approaches to treatment of paediatric ulcerative colitis, but also Dr Vangelis Giamouris, a member of Young ESPGHAN who sits on the Education Committee.

Dr Giamouris has put his head over the parapet: not your usual interviewer, but instead Vangelis will shoot questions at Prof Assa; Prof Assa will shoot answers back; and the listeners can enjoy the firefight.

Vangelis, may the odds be ever in your favour!

Dr Giamouris was granted his medical degree at the University of Thessaly, trained in paediatrics in Athens at the Agia Sofia Children’s Hospital, and at present works at King’s College Hospital (London). He presents three clinical scenarios that involve aspects of paediatric ulcerative colitis to Prof Assa for his perspective on diagnosis and treatment.

Prof Assa is from Israel, where he trained. After a post-graduate fellowship in Toronto at the Hospital for Sick Children, he returned to Israel, where he chairs the Institute for Pediatric Gastroenterology at Kaplan Medical Center in Rehovot. He is also a full professor of pediatrics at Hebrew University in Jerusalem.

In his comments on Dr Giamouris’ clinical vignettes, he illustrates the principles set out in the recently updated ESPGHAN / NASPGHAN guidelines for physicians addressing paediatric ulcerative colitis — guidelines which are cited below.

Now let the games begin!

Literature – pending publicationManagement of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care — An Updated Evidence-based Consensus Guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organization

Management of Paediatric Ulcerative Colitis, Part 2: Acute Severe Colitis — An Updated Evidence-based Consensus Guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organization

Prof. Assa´s favourite song: James Taylor - Fire and Rain

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

A short hop from Stockholm to Helsinki, site of the 2025 ESPGHAN annual meeting, where this interview with Prof Ola Olén was recorded – in Finland, or East Sweden, as it was known until 1809, when the Treaty of Fredrikshamn / Hamina ceded both Finland and parts of both North and West Bothnia to Russia… Only in 1917 was the Grand Duchy of Finland pried away from the fragmenting Russian empire, and, mind you, the Russians, wearing their Soviet hat, stole Karelia back in 1940. Thinking of the state of the world today, we forget history at our peril; it’s never been easy to be a Finn.

Sweden, though, is where Prof Olén is based, and where he mines clinical registries of children with inflammatory bowel disease to identify risks and risk factors for susceptibilities and complications. His particular interest is the question of whether or not the risk of cancer is increased in pediatric inflammatory bowel disease, and if so – what cancers, why, and to what extent, absolute and relative? Of course this raises an important corollary question: What are physicians and families to do with the estimates of risk that his work produces?

An introduction to that work is provided in the references below.

LiteratureOlén O et al. Childhood onset inflammatory bowel disease and risk of cancer: A Swedish nationwide cohort study 1964–2014. BMJ 2017 Sep 20; 358:j3951. Doi: 10.1136/bmj.j3951. PMID: 28931512. PMCID: PMC5605779

Everhov Å et al. Colorectal cancer in childhood-onset inflammatory bowel disease: A Scandinavian register-based cohort study, 1969–2017. J Pediatr Gastroenterol Nutr 2022 Oct 1; 75(4):480–484. Doi: 10.1097/MPG.0000000000003574. Epub 2022 Aug 18. PMID: 36125530

Olén O et al. Increasing risk of lymphoma over time in Crohn’s disease but not in ulcerative colitis: A Scandinavian cohort study. Clin Gastroenterol Hepatol 2023 Nov; 21(12):3132–3142. Doi: 10.1016/j.cgh.2023.04.001. Epub 2023 Apr 13. PMID: 37061104

Everhov Å et al. Cancer incidence in patients with ulcerative colitis naïve to or treated with thiopurine and targeted therapies – a cohort study 2007 to 2022 with comparison to the general population. J Crohns Colitis 2025 Jun 2:jjaf091. Doi: 10.1093/ecco-jcc/jjaf091. Online ahead of print. PMID: 40455688

Dr. Olen´s favourite song: Bara bada bastu” with KAJ.

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

Greetings from Helsinki, capital of yet another nation in which you have to watch your sushi! Boreal circumpolar dining for pescatarians… ring up another aetiology of Vitamin B12 deficiency, and check your erythrocytes’ mean corpuscular volume when you get home.

At JPGN Journal Club, with Dr. Jake Mann, reaching you today from ESPGHAN’s annual meeting, we uniformly are alert against diphyllobothriasis, Scourge of the North. Herring is on the menu this week—wish us luck.

Jake’s choices for today:

From J Pediatr Gastroenterol Nutr, by Kellar et al., writing from a number of North American institutions:“Defining normal bowel wall thickness in children with inflammatory bowel disease in deep remission: A multicenter study on behalf of the pediatric committee of the International Bowel Ultrasound Group (IBUS)”

From Hepatology, by Schwimmer et al., with investigators principally based in San Diego, CA:“Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study”

The JPGN article complements one recently discussed here at Journal Club. That article posed the question: Of what additional value is sonography in assessing extent of small-bowel involvement by inflammatory bowel disease at presentation?

The conclusion: not good enough to displace/replace other techniques, but it does pick up some disease that enteroscopy with biopsy and magnetic resonance imaging studies miss; particularly useful, perhaps, in patients who do not tolerate other techniques well.

The work by Kellar et al. is not the other half of a diptych; that is, it does not pose the question: Of what additional value is sonography in assessing extent of small-bowel involvement by inflammatory disease after clinically successful treatment? That work remains to be done.

A necessary lead-up to that work, however, is to determine by sonography how thick the wall of the bowel is—large and small—after inflammation has receded, with comparisons between regions assessed before as involved and regions assessed before as non-involved. The present study offers standard values likely to be useful in clinical practice.

Of course, aspects of study design permit quibbling—Jake holds both MD and MQ degrees, medicinae ac quibbolae doctissimus!—but overall, truly a pleasure to read and to think through.

Grappling with non-alcoholic fatty liver disease in children—or, more recently, metabolic dysfunction–associated steatotic liver disease (MASLD)—has never been easy. A child with abnormal clinical-laboratory test results that suggest hepatobiliary injury, obtained for no particular reason other than vigilance (as with required determinations of fitness to take part in sports), is referred for specialty evaluation.

Or—more often in the last several years—a fat child is defined prospectively as ill, is “medicalised”, and is referred for specialty evaluation. Colleagues in imaging-study departments say the liver is likely fatty. Oh. Well. Now what?

The natural history of MASLD seems to be largely undefined. So long as that is the case, to act is random—one needs a prognosis, the more detailed the better, to know what to watch out for, to understand how outcomes arise, and to consider intervention.

The authors write:

“The primary objectives of the study were to quantify the mortality rate and identify the causes of death in individuals with pediatric-onset MASLD. Secondary aims were to evaluate the incidence of cirrhosis and the development of extrahepatic outcomes including type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea.”

The authors followed for a mean of 8.5 years, 1,096 children aged 2–18 years who were diagnosed with MASLD between 2000 and 2017. Their findings demonstrate considerable hepatic morbidity and extrahepatic co-morbidity, with an increased death rate.

Whilst the population that they studied was 80% “Hispanic”, which precludes facile extrapolation of their conclusions to other ethnic groups—Mexican-American boys notoriously are butterballs, victims of the cultural conviction FOOD = LOVE—the authors’ findings will be, and perhaps should be, used to warrant screening and intervention (diet, exercise, GLP-1 receptor agonists), and thus are worth attention.

LiteratureKellar A et al. Defining normal bowel wall thickness in children with inflammatory bowel disease in deep remission: A multicenter study on behalf of the pediatric committee of the International Bowel Ultrasound Group (IBUS). J Pediatr Gastroenterol Nutr. 2025 Apr 29. doi: 10.1002/jpn3.70049. Online ahead of print. PMID: 40296563

Schwimmer JB et al. Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study. Hepatology. 2025 Apr 22. doi: 10.1097/HEP.0000000000001357. Online ahead of print. PMID: 40262118

Greetings from Helsinki, where your ESPGHAN podcast team has taken the opportunity to buttonhole as many learned, skilled, and experienced paediatric gastroenterologists and hepatologists as possible for interviews!

This note accompanies a conversation recorded there with Dr. Roberto Canani, an expert in paediatric food allergy. In this podcast, however, he steps away from what might be considered the principal theme of his expertise—namely, immunologic dysregulation at the enteric mucosa and beyond.

Instead, he addresses three key questions:

1. What are ultraprocessed foods?

2. What evidence indicates that such foods facilitate the occurrence of paediatric gastrointestinal disorders?

3. What are the mechanisms of action by which such foods might contribute to paediatric gastrointestinal disease?

He refers to three relevant articles that help frame and answer these questions:

• Srour B et al. Ultra-processed foods and human health: From epidemiological evidence to mechanistic insights. Lancet Gastroenterol Hepatol. 2022 Dec; 7(12):1128–1140. doi: 10.1016/S2468-1253(22)00169-8. Epub 2022 Aug 8. PMID: 35952706

• Lane MM et al. Ultra-processed food exposure and adverse health outcomes: Umbrella review of epidemiological meta-analyses. BMJ. 2024 Feb 28; 384:e077310. doi: 10.1136/bmj-2023-077310. PMID: 38418082; PMCID: PMC10899807

• Canani RB et al. Ultra-processed foods, allergy outcomes and underlying mechanisms in children: An EAACI task force report. Pediatr Allergy Immunol. 2024 Sep; 35(9):e14231. doi: 10.1111/pai.14231. PMID: 39254357

Concern is growing about the effects of ultraprocessed foods on us all. Today, Dr. Canani helps us understand what is currently known and how to integrate that knowledge into clinical care.

Hot off the press – fresh from Helsinki – your ESPGHAN podcast team has interviewed Dr. Elena Cernat, a paediatric gastroenterologist originally from Romania, via Spain, and now working in Leeds.

Dr. Cernat has handpicked six interesting abstracts from this year’s ESPGHAN annual meeting to discuss with us (she found many more, of course, but podcast time constraints – you’ll understand). She explains why she chose these particular abstracts… though it’s entirely possible your assessments may differ. Judge for yourselves!

Abstracts (in order of discussion):

1. A cfCHIP-SEQ Liquid Biopsy for the Diagnosis of Autoimmune Hepatitis in Children

Publication: H-OP024 | Topic: AS02. Hepatology

This study explores the use of cfChIP-seq, a liquid biopsy technique, to diagnose autoimmune hepatitis (AIH) in children, offering a non-invasive alternative to liver biopsy. Researchers found distinct immune-related transcriptional activity in AIH patients, identifying a gene expression signature (“AIH score”) that distinguishes AIH from other liver diseases with 90% accuracy.

2. Gut Microbiota Response to Ileal Bile Acid Inhibitor Therapy in Children with Progressive Familial Intrahepatic Cholestasis

Publication: H-OP012 | Topic: AS02. Hepatology

Researchers evaluated how IBAT inhibitors and liver transplantation (LT) impact gut microbiota in PFIC patients. While LT restored microbiota function closer to normal, IBAT inhibitors did not significantly improve bile acid metabolism or microbiota composition—although changes were associated with clinical response in some cases.

3. A Set of Serum Proteomic Biomarkers Differentiates Celiac Children from Age and HLA-Matched Controls

Publication: G-OP010 | Topic: AS01. Gastroenterology

This study identified a panel of eight inflammation-related serum proteins that can differentiate children with celiac disease from HLA-matched healthy controls with over 90% accuracy. This holds promise for reducing the need for intestinal biopsy in diagnosis.

4. Long-Term Maintenance Treatment with Vedolizumab in Pediatric IBD: A Three-Year Follow-Up of the Prospective Multicenter VEDOKIDS Study

Publication: G-OP070 | Topic: AS01. Gastroenterology

A three-year prospective study found that vedolizumab is a safe and effective long-term maintenance therapy, particularly in pediatric UC (ulcerative colitis) patients. Early clinical remission (by week 6) was the best predictor of sustained remission over three years.

5. Mechanisms of Fetal Regulatory B Cell Induction by 2’-Fucosyllactose Supplementation During Pregnancy for Allergy Prevention

Publication: N-OP013 | Topic: AS03. Nutrition

This experimental study in mice suggests that prenatal supplementation with 2'-fucosyllactose (2’FL) enhances fetal immune tolerance by increasing B10 regulatory cells via maternal microchimerism. These findings may shed light on allergy prevention mechanisms starting in utero.

6. D-Lactate in Pediatric Patients on Enteral and Long-Term Parenteral Nutrition

Publication: N-OP033 | Topic: AS03. Nutrition

D-lactate levels were compared across pediatric patients receiving long-term parenteral nutrition, those post-intestinal adaptation, and healthy controls. Elevated D-lactate was linked to specific clinical settings like SBS, and genetic analysis was used to investigate possible metabolic contributors.

Elena´s song she brought from Finnland : Loituma - Ievan Polkka https://open.spotify.com/track/7aJMmhcw04NrO6whqwL23G?si=cc082143da8546bc

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

Dr Rosan Meyer, reared and educated in South Africa and for some years active in London as a paediatric dietitian, is the guest of ESPGHAN today.  Her particular interest lies in the Protean gastrointestinal manifestations of food allergy and how to intervene to reduce or to eliminate them.  Today she asks us to consider :  

-- Are feeding difficulties adequately recognised and treated in children with food allergy ?

-- What is the context of the immune-supportive diet in addressing food allergy ?

-- What advances have been made around food allergy and tolerance induction ?

She offers us four articles to assist us in coming to grips with these issues.  A difficult field, and, one hopes, an interesting discussion.

Literature

Vlieg-Boerstra B et al.  The immune-supportive diet in allergy management :  A narrative review and proposal.  Allergy 2023 Jun 78(6):1441-1458.  DOI :  10.1111/all.15687.  Epub 2023 Apr 4.  PMID:  36802268

Meyer R et al.  World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update – VII – Milk elimination and reintroduction in the diagnostic process of cow’s milk allergy.  World Allergy Organ J 2023 Jul 2416(7):100785.  DOI :  10.1016/j.waojou.2023.100785.  PMID :  37546235.  PMCID :  PMC10401347

Meyer R et al.  Diagnosis and management of food allergy-induced constipation in young children — an EAACI position paper.  Pediatr Allergy Immunol 2024 Jun35(6):e14163.  DOI :  10.1111/pai.14163. PMID :  38825829 

Chebar-Lozinsky A et al.  Assessing feeding difficulties in children presenting with non-IgE-mediated gastrointestinal food allergies—a commonly reported problem.  Nutrients 2024 May 2216(11):1563.  PMID :  38892497.  PMCID :  PMC11173616.    DOI :  10.3390/nu16111563 

Hello! The JPGN Journal Club, led by Dr. Jake Mann, is back — in your speakers, your earbuds, or maybe even over the airport tannoy… well, probably not the last one. Anyway, it's good to be back in touch.

Please visit https://www.espghan.org/knowledge-center to explore current offerings, and don't forget ESPGHAN’s annual meeting, taking place May 14–17 in Helsinki.

1.From Journal of Pediatric Gastroenterology and Nutrition (JPGN):Ritchie et al. (Aberdeen, UK, and Christchurch, NZ) –"Role of Noncontrast-Enhanced Abdominal Ultrasound in the Diagnostic Assessment of Pediatric Inflammatory Bowel Disease"

• A retrospective review of 47 children in New Zealand with inflammatory bowel disease (IBD).

• Examined the contributions of endoscopy, biopsy, magnetic resonance enterography (MRE), and noncontrast sonography (NCS) in diagnosing small-bowel involvement.

• Findings:

  • 14 children had no small-bowel disease.

  • Of the 33 with small-bowel involvement:

    • 19 had findings on NCS.

      • In 7 cases, NCS detected disease that endoscopy, biopsy, and MRE missed.

      • In 12 cases, NCS confirmed disease found by other modalities and found additional sites of involvement.

    • In 14 cases, NCS failed to detect small-bowel disease that other methods identified.

• Conclusion:NCS alone missed about two-fifths of cases but expanded diagnosis in about one-fifth.

2. From Nature:Rosenberger et al. (Czechia, Denmark, Germany) –"Deep Visual Proteomics Maps Proteotoxicity in a Genetic Liver Disease"

• Focused on alpha-1-antitrypsin storage disorder (A1ASD), where mutations in SERPINA1 cause alpha-1-antitrypsin (A1A) to accumulate in liver cells.

• Mechanisms of injury ("proteotoxicity") were unclear.

• The study used staining, microdissection, and mass spectrometry to analyze individual hepatocytes.

• Key findings:

  • Upregulation of the unfolded protein response.

  • Downregulation of hepatocellular synthesis and secretion processes.

  • Strong activation of peroxisomes in samples from individuals with less fibrosis; this activation declined in cases with more fibrosis.

• Implication:The authors speculate that peroxisome activators might help modulate disease progression.

• Limitations:The study focused on adult samples (ages 40–80), leaving unanswered how A1ASD leads to cholestasis in some infants but not others.

• Ritchie K, et al. Role of Noncontrast-Enhanced Abdominal Ultrasound in the Diagnostic Assessment of Pediatric Inflammatory Bowel Disease. JPGN, 2025 Apr 9.PMID: 40201985 | DOI: 10.1002/jpn3.70044

• Rosenberger FA, et al. Deep Visual Proteomics Maps Proteotoxicity in a Genetic Liver Disease. Nature, 2025 Apr 16.PMID: 40240610 | DOI: 10.1038/s41586-025-08885-4