The incidence of pediatric inflammatory bowel disease (PIBD) has risen worldwide, creating significant challenges for healthcare professionals. Compared with adult-onset inflammatory bowel disease, PIBD often presents with more extensive intestinal involvement, a more aggressive course, and complications affecting growth and puberty, making timely disease control critical for PIBD. However, treatment selection remains largely empirical, and many patients fail to respond to initial therapy. Additionally, conventional experimental models, including 2-dimensional cell culture and animal systems, often fail to reproduce the complexities of human intestinal tissues. These limitations highlight the need for human-relevant experimental platforms capable of capturing patient-specific disease biology and supporting precise therapeutic decision-making in PIBD. In this context, patient-derived intestinal organoids have emerged as valuable tools for studying disease mechanisms and evaluating therapeutic responsiveness in patients with PIBD. Organoid-based systems enable direct investigations of epithelial barrier dysfunction, inflammatory signaling, metabolic alterations, and genotype-associated molecular features that provide insight into tissue-level disease heterogeneity. Emerging data suggest that ex vivo drug responses observed in patient-derived intestinal organoids may parallel clinical treatment outcomes, indicating their potential to support more informed therapy selection in PIBD. Despite these advances, current organoid models have important limitations including the absence of immune, stromal, and vascular components as well as challenges related to standardization, scalability, and cost-effectiveness. To overcome these limitations, next-generation platforms incorporating immune cell coculture systems, microbiota, and microfluidic technologies are being developed to better replicate the complexity of the host intestinal microenvironment. As these integrated systems evolve, intestinalorganoids are expected to become increasingly powerful tools for disease modeling, biomarker discovery, and therapeutic response prediction, ultimately supporting the development of personalized and effective treatment strategies for PIBD.
Stress ulcer prophylaxis (SUP) is widely used in critically ill children; however, evidence for benefit is limited and previous reviews reached conflicting conclusions, particularly regarding mortality. Here we aimed to reassess the benefits and harms of SUP in critically ill children and reconcile the conflicting conclusions of previous reviews. We searched the PubMed/MEDLINE, CENTRAL, Scopus, Web of Science, and Igaku Chuo Zasshi databases from inception to May 20, 2026, for randomized and nonrandomized studies comparing SUP with placebo or no treatment in critically ill children. Risk of bias was assessed with outcome-specific risk of bias 2 and Risk Of Bias In Non-randomized Studies of Interventions, version 2 (ROBINS-I V2) and certainty with Grading of Recommendations Assessment, Development, and Evaluation; random-effects models pooled outcomes reported in ≥2 studies. The protocol was registered (PROSPERO CRD420251074125), and reporting followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) 2020 guidelines. Eighteen studies were included (7 randomized, 11 nonrandomized); all nonrandomized studies had a critical risk of bias (confounding by indication) and were excluded from synthesis. The evidence was very uncertain for all outcomes. For the primary outcome, upper gastrointestinal bleeding, no reduction was found (5 trials, n=713; risk ratio [RR], 1.06; 95% confidence interval [CI], 0.76-1.47; I²=0%), with similarly inconclusive estimates for clinically significant gastrointestinal bleeding (RR, 0.81; 95% CI, 0.20-3.26), mortality (RR, 1.12; 95% CI, 0.73-1.71), and ventilator-associated pneumonia (RR, 1.13; 95% CI, 0.78-1.63); the previously reported mortality signal was not reproduced. An exploratory analysis suggested an increased incidence of central line-associated bloodstream infection (CLABSI; 2 trials, n=212; RR, 2.47; 95% CI, 1.24-4.90). By formally appraising every non-randomized study with ROBINS-I V2 rather than excluding them by design, this review reconciles earlier conflicting syntheses: across the largest randomized evidence base to date, prophylaxis conferred no demonstrable benefit, and the earlier mortality signal was not reproduced. With very low overall certainty, the evidence neither showed a benefit nor excluded an exploratory signal of an increased incidence of CLABSI. Accordingly, the current evidence is insufficient to support the routine use of SUP.
Background Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious hyperinflammatory condition that can follow a sudden acute respiratory syndrome coronavirus 2 infection. Although several inflammatory markers are used to guide its clinical management, biomarkers that reflect immunomodulatory therapy responses remain limited. Purpose Evaluate intrapatient changes in serum soluble membrane attack complex/C5b-9 levels before and after immunomodulatory therapy in children with MIS-C. Methods In this longitudinal observational study, paired serum samples from 100 children diagnosed with MIS-C across 3 tertiary care centers in India were analyzed for soluble C5b-9 (sC5b-9) concentrations before the initiation of immunomodulatory therapy and at clinical recovery. Intrapatient changes were evaluated using paired nonparametric statistical methods. Clinical phenotypes at presentation were documented and explored in relation to baseline sC5b-9 levels. Results Serum sC5b-9 concentrations significantly declined following immunomodulatory therapy across the cohort (P<0.0001). Elevated pretherapy sC5b-9 levels were observed in patients presenting with shock, multiorgan dysfunction, or cardiac involvement. Although most patients exhibited reduced sC5b-9 levels following therapy, the magnitude of the change varied among individuals, with a subset showing persistently elevated levels at discharge. Conclusion Serum sC5b-9 levels decreased after immunomodulatory therapy in children with MIS-C, suggesting its potential utility as a longitudinal marker of treatment response. The interpretation of absolute concentrations is limited by the serum-based sampling methodology; however, consistent intrapatient trends support further investigations using optimized complement sampling protocols.
Background:Nationwide data on the incidence of central precocious puberty (CPP) and premature thelarche (PT), a benign variant of pubertal development, are limited. Purpose:To evaluate trends in CPP and PT incidence among Thai children before, during, and after the COVID-19 pandemic. Methods:This cross-sectional population-based study used National Health Security Office (NHSO) claims data from 2018 to 2024. CPP and PT were identified using ICD-10-TM (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification) codes. Annual incidence rates (AIRs) were calculated for each NHSO-insured population, while incidence rate ratios (IRRs) were estimated using quasi-Poisson regression. Results:A total of 6,782 girls and 189 boys with CPP, and 1,594 girls with PT, were included. Among girls, the CPP AIR increased from 15.0 per 100,000 person-years in 2018 to 51.7 in 2021 and remained elevated during 2022-2024 (44.1-47.7). The IRR was 2.27 (95% confidence interval [CI], 1.82-2.83) for pandemic versus prepandemic, and 1.06 (95% CI, 0.89-1.26) for postpandemic versus pandemic period. An age-stratified analysis showed the greatest increase among girls aged 8 to <9 years. Among boys, the CPP AIR remained low and stable (0.6-1.0 per 100,000 person-years). The female-to-male IRR was 43.0 (95% CI, 33.5-55.3). The incidence of PT in girls increased from 7.2 in 2018 to 14.6 per 100,000 person-years in 2024, with the largest increase observed among those aged 7 to <8 years. Conclusion:The incidence of CPP among Thai girls increased during the COVID-19 pandemic and remained elevated thereafter, whereas the incidence of PT increased gradually. Both trends were most pronounced in peripubertal age groups. Further studies are required to determine whether these patterns reflect pandemic-related factors or an earlier onset of puberty.
Background:The gut microbiota plays an important role in childhood growth and metabolic regulation and may interact with the growth hormone (GH)-insulin-like growth factor-1 axis. However, the gut microbiota characteristics in children with GH deficiency (GHD) are poorly understood. Purpose:This study aimed to compare the gut microbiota composition and predict the functional profiles of Korean children with GHD and those growing normally. Methods:In this pilot case-control study, fecal samples were collected from children with biochemically confirmed GHD and age- and sex-matched healthy controls. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Microbial alpha and beta diversities, taxonomic compositions, and differentially abundant taxa were evaluated. Functional profiles of the gut microbiome were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States based on the Kyoto Encyclopedia of Genes and Genomes database. Results:A total of 34 children (11 with GHD, 23 healthy controls) were included in the study. Alpha diversity indices did not differ significantly between groups, whereas beta diversity indices demonstrated a significant intergroup difference (permutational multivariate analysis of variance, P=0.003). At the phylum level, the GHD group showed a higher relative abundance of Proteobacteria and lower abundance of Bacteroidetes. At lower taxonomic levels, taxa including Enterobacteriaceae, Enterobacter, and Citrobacter, which are often associated with dysbiosis, were enriched in the GHD group, whereas beneficial taxa such as Bacteroides and Ruminococcaceae family members were reduced. A functional prediction analysis revealed enrichment of pathways related to adenosine triphosphate-binding cassette transporters, phosphotransferase systems, quorum sensing, and bacterial motility in children with GHD. Conclusion:Children with GHD showed altered gut microbiota composition and predicted microbial functional pathways despite similar overall microbial diversity. These findings suggest a potential association between gut microbiota alterations and GHD and warrant further investigation in larger well-designed studies.
Background:Neutrophil extracellular traps (NETs) contribute to cancer progression; however, their value as systemic biomarkers and therapeutic targets in pediatric cancers remains unclear. Purpose:To evaluate circulating NET markers as minimally invasive diagnostic and prognostic biomarkers in pediatric cancer and explore the restoration of NET degradation as a therapeutic strategy using recombinant human deoxyribonuclease I (DNaseI). Methods:In this prospective cohort study, plasma samples from 182 pediatric patients with diverse tumor types and 10 age-matched healthy controls were analyzed. Circulating NET markers, including cell-free DNA, calprotectin, neutrophil elastase, citrullinated histone H3-DNA complexes, and DNaseI activity, were quantified. NETs were assessed in tumor tissue samples using immunofluorescence. The diagnostic performance and prognostic value were evaluated using receiver operating characteristic and survival analyses, respectively. The ability of patient plasma to degrade NETs and the effects of recombinant human DNaseI supplementation were examined in vitro. Results:Plasma cell-free DNA and calprotectin levels were significantly higher in pediatric patients with cancer than in controls, particularly in high-risk patients. Cell-free DNA showed high diagnostic accuracy, whereas calprotectin and DNaseI activity discriminated between high- and low-risk patients and were associated with adverse outcomes. NETs were detected in tumor tissues with heterogeneous distribution and no consistent association with prognosis. Plasma from high-risk patients exhibited impaired NET degradation, which was restored in vitro using recombinant human DNaseI. Conclusion:Circulating NETs, especially cell-free DNA and calprotectin, show promise as noninvasive diagnostic and prognostic biomarkers for pediatric cancers. Reduced DNaseI activity identified a potentially targetable mechanism, supporting further investigation of DNaseI-based therapeutic strategies for high-risk pediatric tumors.
Background:Biliary atresia (BA) is a common cause of cirrhosis in children, and serious bacterial infections may worsen clinical outcomes. Purpose:To study the characteristics, associated factors, and outcomes of infections in children with cirrhosis secondary to BA. Methods:A retrospective cohort study was conducted in children aged <18 years with cirrhosis due to BA between 2014 and 2023. Patients were categorized as having proven/suspected bacterial infection, presumed viral infection, or no documented infection. The clinical characteristics, associated risk factors, predictive models, and native liver survival outcomes, including liver transplantation (LT) and death, were analyzed. Results:Among 150 children, 94 (62.7%) had 222 infection episodes and 249 had infection-related diagnosis. Of the 222 episodes, 143 (64.4%) were classified as proven/suspected bacterial infections; cholangitis was the most common bacterial diagnosis (39.7%). Univariate analysis showed that proven/suspected bacterial infection was associated with higher pediatric end-stage liver disease scores at the first visit and during fever episodes and with higher total and direct bilirubin levels during fever episodes. C-reactive protein (CRP) cutoff of 31 mg/L yielded 75.4% sensitivity, 68.2% specificity, and an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI], 0.69-0.90) for distinguishing proven/suspected bacterial from presumed viral infections. Overall, 54% of patients underwent LT, 24% survived with their native liver, 8% died, and 14% were lost to follow-up. After adjustment for disease severity and infection history before referral, proven/suspected bacterial infection was associated with lower native liver survival (adjusted hazard ratio, 1.88; 95% CI, 1.51-2.33). Conclusion:Infections are common in children with cirrhosis due to BA. Serum CRP may help distinguish proven/suspected bacterial from other infections. Bacterial infections were associated with lower native liver survival; therefore, appropriate management and prevention may improve native liver survival.
Background: Genotype-phenotype correlations in Wilson disease (WD) have so far been inconclusive.Purpose: ATP7B variants with loss of function (LOF) may have a different trajectory. Since genotypes in Asia differ from the West, we aimed to correlate LOF variants of ATP7B with the severity and outcome of hepatic WD.Methods: Patients with a confirmed diagnosis of WD (Leipzig criteria ≥4) were prospectively enrolled. Genetic sequencing of ATP7Bmutations was assessed by Whole-exome sequencing. For patients with variants of uncertain significance, Sanger sequencing was additionally performed on their parents to identify the inherited variants. In silico analyses were used to predict the pathogenicity of variants. Mutations that resulted in at least one truncation (nonsense, frameshift, splice site, deletions) and nontruncation (missense, synonymous) protein were defined as LOF and no LOF (NLF) respectively. Phenotypes, biochemical parameters, and outcomes were analyzed.Results: One hundred sixteen hepatic WD children (84 boys, median age at diagnosis 8.9±3.3 years) with biallelic ATP7B mutations (62 different variants) were enrolled. The most common LOF (n=79) and NLF (n=37) variants were c.813C>A and c.3809A>G. Advanced liver disease (76% vs. 4%, P=0.004), portal hypertension (44% vs. 24%, P=0.03), neurological (39% vs. 16%, P=0.01) and renal involvement (44% vs. 13%, P=0.01) were significantly higher in LOF than in NLF. c.813C>A had higher serum exchangeable copper (6.8±4.4 μmol/L vs. 1.4±3.5 μmol/L, P=0.04) and lower disappearance of the Kayser-Fleischer ring (4% vs. 49%, P= 0.01) than c.3809A>G variants. Over a follow-up of 6.1±4.7 years, a single LOF variant did not show a poorer liver or overall outcomes in comparison to ≥2 LOF variants.Conclusion: A single ATP7B LOF variant, especially c.813C>A was associated with advanced liver disease, portal hypertension, and extrahepatic involvement. LOF variants did not affect liver or overall outcomes.
Background:Intravenous immunoglobulin (IVIG) formulations used to treat Kawasaki disease differ markedly in sodium content; however, the clinical significance of this factor remains unclear. Purpose:Here we investigated whether sodium content influences electrolyte changes and short-term clinical outcomes of Kawasaki disease. Methods:This single-center retrospective cohort study included 744 children with first-episode Kawasaki disease treated with 2-kg IVIG in 2010-2020. The patients were categorized into high-sodium (Glovenin-I or Venilon-I) and low-sodium (Venoglobulin IH) groups. Serum electrolytes, total protein, and immunoglobulin G levels were measured before and after IVIG administration. Outcomes included additional IVIG administration and the presence of coronary artery lesions. Results:Compared to the low-sodium group, the high-sodium group had significantly increased serum sodium (2.9±3.2 mEq/L vs. 1.7±2.7 mEq/L) but significantly decreased serum potassium (-0.13±0.50 mEq/L vs. -0.03±0.49 mEq/L) levels after IVIG therapy. After its administration, hyponatremia occurred more often in the low-sodium group (4.4% vs. 0.3%), whereas hypokalemia occurred more frequently in the high-sodium group (9.9% vs. 5.5%). Total protein, immunoglobulin G, and albumin levels were higher in the low-sodium group. The rates of additional IVIG use and coronary artery lesions did not differ significantly between groups. Conclusion:Our findings demonstrate that the sodium content of IVIG contributes to distinct changes in electrolyte and protein concentrations during the acute phase of Kawasaki disease. However, these biochemical differences were not associated with short-term clinical outcomes. Awareness of formulation-specific profiles may help clinicians interpret laboratory findings appropriately during IVIG therapy.
Background Home phototherapy (HPT) is an alternative to inpatient phototherapy (IPT) for the treatment of neonatal jaundice; however, comparative data remain limited on the effectiveness of phototherapy (PT) devices across care settings. Purpose To compare the efficacy and safety of HPT using a fiberoptic light-emitting diode (LED) PT blanket with those of IPT using overhead LED PT in neonates with jaundice. Methods This retrospective cohort study included neonates born at ≥35 weeks' gestation who were prescribed treatment for jaundice at a tertiary academic medical center in Thailand between August 1, 2023, and December 31, 2025. Infants who underwent either HPT or IPT were included. The bilirubin reduction, treatment success, and adverse event rates were compared between groups. Results A total of 100 PT sessions (89 neonates) were analyzed, including 55 HPT sessions (50 infants) and 45 IPT sessions (43 infants). Some infants received both treatment modalities during separate sessions, and each session was analyzed according to the administered PT modality. The mean bilirubin reduction rate was significantly lower in the HPT versus IPT group (0.18±0.10 mg/dL/hr vs. 0.29±0.08 mg/dL/hr, P<0.001). This finding remained consistent in uni- and multivariate multilevel mixed-effects linear regression analyses, accounting for repeated PT sessions, intergroup crossover, and potential confounders (coefficient, -0.116; 95% confidence interval, -0.146 to -0.086; P<0.001). Treatment success was achieved in all infants except for one in the HPT group who experienced an increase in total serum bilirubin following treatment that subsequently resolved after conversion to IPT. No serious PT-related complications were observed in either group. Conclusion In routine clinical practice, fiberoptic home PT was safe but less effective than hospital-based LED PT at reducing bilirubin levels, supporting its use in carefully selected neonates with appropriate monitoring and follow-up.
