JPGN Journal Club May 2024: Genetic Insights in Cystic Fibrosis Liver Disease and Linaclotide for Pediatric Functional Constipation

Here again is JPGN Journal Club. It’s Spring, people!  Asparagus! Strawberries! White wine! All of these can be enjoyed as an ESPGHAN podcast listener, so let’s get at it :  Raise your sauce béarnaise-laden forks, your Sancerre glasses, and your play-volume settings. Dr Jake Mann has chosen for today from Hepatology, by Stonebraker et al., Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis.  Genomes of substantial numbers of CFTR  disease patients, both with and without substantial liver disease (the former collected principally by centres in North Carolina and a centre In Ontario), were sieved for associations with the relatively uncommon but clinically burdensome features of biliary-tract injury and of malperfusional injury.  Indeed some were found, but what do they tell us about “novel mechanisms” ?  Hand-waving ensues.  A proof-of-concept study, then.   Jake also has chosen, from J Pediatr Gastroenterol Nutr, by Di Lorenzo et al., Clinical trial :  Randomized controlled trial of linaclotide in children aged 6−17 years with functional constipation.  “News you can use”, perhaps:  Stooling improved to a respectable extent in those given higher doses of the agent, with the dosage ceiling still high above those employed so far. Response as a new discriminator, a new classifier, to permit dissection and separation of forms of functional constipation?   Well, Jake as advocate will tell us what strengths and flaws he perceives in the two studies. Listen up, and don’t omit to pass the strawberries!