JPGN reports最新文献

Glucagon-like peptide-2 (GLP2) acts on the GLP2 receptor (GLP2R) and plays a role in intestinal growth and adaptation. The endogenous actions of GLP2R do not have an established association with human disease, although mouse-knockout models in a stressed state show enhanced susceptibility to small bowel injury, increased morbidity, mortality, and abnormal host-bacterial interactions. We report an 11-month-old female with multiple intensive care unit admissions for severe metabolic acidosis due to profuse nonbloody diarrhea in the context of various infections. She had normal growth, lab testing, and stooling patterns between illnesses. Trio-whole genome sequencing revealed homozygous nonsense variants resulting in nonfunctional GLP2R. This is the first known human documented with a GLP2R-deficient phenotype, resulting in clinical illness, which correlates with the findings in the GLP2R mouse knockout model and furthers our understanding of GLP2R and the action of teduglutide, a GLP2 analog used for the treatment of short bowel syndrome.

Individuals with intestinal failure are at risk of micronutrient deficiencies, including iodine, an essential trace element critical for thyroid hormone production. In patients entirely dependent on parenteral nutrition, options for replenishing and maintaining iodine levels are severely restricted as oral forms have limited absorption, and intravenous alternatives are unavailable. Ethiodized oil (Lipiodol-TM) is an iodinated contrast agent with an unusually long half-life that can be given orally or injected into a target organ. We report the successful use of intramuscular injection of ethiodized oil in treating goiter in a patient with total entero-colectomy and in sustaining long lasting thyroid function for over 5 years.

Hepatotoxicity is an under-recognized and potentially fatal side effect of high-dose methotrexate (HDMTX) chemotherapy, and this risk is compounded in children with metabolic dysfunction-associated steatotic liver disease and/or metabolic-associated steatohepatitis. We present the case of a 12-year-old obese, Hispanic male with elevated hepatic transaminases of unknown etiology at initiation of high-risk B-cell acute lymphoblastic leukemia chemotherapy. He developed acute kidney injury within 24 hours of receiving intravenous HDMTX which progressed to acute hepatic failure. Liver biopsy confirmed methotrexate toxicity aggravated by undiagnosed metabolic dysfunction-associated steatotic liver disease. Rapid deterioration precluded liver transplantation, and he died 21 days after HDMTX treatment. This case highlights the need for comprehensive hepatic evaluation in patients with known or suspected liver disease when administering HDMTX. Dialysis should be considered if delayed methotrexate clearance occurs due to potential for rapid, irreversible hepatotoxicity.

Objectives: Upadacitinib (UPA), a selective Janus kinase-1 inhibitor, has demonstrated efficacy in inducing and maintaining remission in moderate to severe ulcerative colitis (UC) in adults. Current standard management for acute severe ulcerative colitis (ASUC) involves intravenous corticosteroids (IVCS) followed by infliximab (IFX) salvage therapy. Limited data exist on the utility of UPA in ASUC, particularly in adolescents. This case series reports the use of UPA as salvage therapy in hospitalized adolescents experiencing ASUC refractory to IFX.

Methods: We performed a retrospective chart review of hospitalized patients with ASUC who received UPA as salvage therapy after initiation of IVCS and failure of IFX.

Results: Three adolescents were hospitalized with ASUC for which IFX infusion treatments were unsuccessful. Initiation of UPA enabled patients to improve their Pediatric Ulcerative Colitis Activity Index scores to ≤35 and be discharged home. Hospitalization course, complications, and follow-up information are provided.

Conclusion: UPA is a promising short-term salvage therapy in adolescent ASUC cases resistant to conventional treatments. Prospective studies are warranted to elucidate its long-term efficacy and safety in this specific population. These findings provide a novel therapeutic avenue for managing ASUC in adolescents, offering hope for those encountering treatment challenges.

Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare disorder characterized by chronic cholestasis usually progressing to end-stage liver disease (ESLD) within the first two decades of life. PFIC-3 is caused by pathogenic genetic variants of the ATP-binding cassette 4 (ABCB4) gene with variable inheritance; the most common is autosomal recessive. We present two cases of PFIC-3 with genetic testing confirming a novel genetic variant in ABCB4 with homozygous genotype c.779 T > C, p.L260P. Both individuals are from mainland Southeast Asia and have a clinical picture consistent with cholestasis progressing to ESLD.

Gallbladder volvulus (GV) involves the rotation of the gallbladder along its axis, resulting in torsion. This pathology is rare, more commonly found in elderly females, but can occasionally occur in pediatric patients. Diagnosis is challenging due to often atypical symptoms, with imaging and laboratory findings typically nonspecific. Prompt surgical intervention is necessary when GV is suspected to prevent significant systemic illness. Laparoscopic cholecystectomy has proven to be safe and effective in pediatric cases. In this report, we present a pediatric case of GV, initially misdiagnosed as viral-induced acalculous cholecystitis, which was effectively managed using laparoscopic cholecystectomy.

Inflammatory bowel disease (IBD) is a chronic condition, characterized by recurrent inflammation of the gastrointestinal tract. While the primary focus of IBD management consists in controlling gastrointestinal symptoms, IBD also presents an increased risk of thromboembolic complications. Tumor necrosis factor alpha (TNF-α) inhibitors, namely infliximab, have become increasingly common in the management of multiple chronic inflammatory diseases such as IBD. However, recent studies have shown an association between treatment with infliximab and an increased thrombotic risk. We report an unusual case of retinal vein thrombosis in a patient with ulcerative colitis (UC) that occurred during infliximab infusion. This case highlights the need to remain vigilant when administering infliximab to individuals with IBD, particularly those with additional risk factors for thrombosis.

Extraintestinal manifestations in inflammatory bowel disease (IBD) most frequently involve the joints, skin, and organs such as the liver and pancreas. Inflammation of the aorta is less commonly described in pediatrics, although it has been described in adults. We report a case of an adolescent female with Crohn's disease who presented with worsening diarrhea, vomiting, and weight loss, found to have aortitis on imaging. We review the pathogenesis and clinical features of Takayasu arteritis, as well as some of its similarities to IBD to raise awareness, as early detection of this less-known extraintestinal manifestation has been associated with better outcomes.

Management of choledochoceles (type III choledochal cysts) in children varies. We highlight the potential role of endoscopic management of choledochoceles with cystostomy and biliary sphincterotomy through a series of three successfully treated pediatric patients aged 12-13 at our tertiary center. Patients presented with symptoms including abdominal pain and pancreatitis. Choledochoceles were identified by preprocedure imaging on magnetic resonance imaging, with sizes ranging between 7 and 15 mm in maximal diameter. Histology revealed two choledochoceles lined by biliary epithelium and one by intestinal epithelium. Clinical improvement was sustained at a 2-year follow-up, with radiographic resolution on repeat imaging and normal tumor markers. We conclude that endoscopic management of choledochoceles with cystostomy and biliary sphincterotomy is a therapeutic option in children and can lead to sustained resolution of associated symptoms. While there is some lifetime risk of malignancy with choledochal cysts, malignancy in choledochoceles is rare.

A recent nonsyndromic phenotype, newly linked to mutations in the ZFYVE19 gene, is characterized by the appearance of cholestasis accompanied by an increase in serum gamma-glutamyltranspeptidase (GGT) from infancy or early childhood. Affected individuals generally present with hepatosplenomegaly and may develop portal hypertension. The disease is thought to be the result of cholangiocyte-specific ciliary dysfunction, indicating a ciliopathy that appears to be limited to the liver. Here, we describe the case of an infant born to first-degree consanguineous parents, in whom neonatal cholestasis accompanied by elevated GGT led to the discovery of a ZFYVE19 deficiency. The diagnosis was established following an in-depth analysis of the complete exome sequencing.