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: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: 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.
Background: Despite advances in medical technology, the number of children with complex chronic conditions (CCC) is increasing. Pediatric critical care involves high cost and low revenue. To address this issue, the Korean government designated and financially supported Specialized Public Medical Centers for Children (SPMCCs). However, rigorous evidence of their effectiveness remains limited.Purpose: We analyzed 30-day readmission rates to determine whether SPMCC designations contributed to improvements in pediatric critical quality of care and assess the presence of a measurable policy effect on readmission reduction.Methods: We included pediatric patients aged 0–18 years with a principal diagnosis of CCC and received care at SPMCCs between 2015 and 2021 using data from the customized National Health Insurance Service database. We applied an interrupted time series analysis with segmented regression to estimate the immediate level and postintervention slope changes in 30-day readmission rates following SPMCC designation. SPMCCs were classified into first and second designation groups based on the timing of their designation.Results: The 30-day readmission rates increased over time in the first and second designation groups. The first group showed a nonsignificant immediate level change at designation (-2.65 percentage points [pp]) but a significant decline in the postintervention slope of observed rates (-1.72 pp per quarter; P<0.001). Likewise, the adjusted 30-day readmission rates showed a nonsignificant level change (-0.75 pp; P=0.69) and a significant slope decline (-1.84 pp/quarter; P<0.001). The second group showed downward trends in 30-day readmission rates after designation in the observed and adjusted analyses; however, these trends were not statistically significant.Conclusion: The SPMCC designation was associated with a meaningful reduction in the trajectory of 30-day readmissions in the first group, providing evidence of a policy-induced reduction in readmissions. These findings highlight the importance of a sustained government investment in maintaining and expanding improvements and strengthening pediatric critical care services.
Pediatric allergic rhinitis, among the most common chronic allergic diseases in children and adolescents, represents a significant public health burden in Korea and other countries. Allergic rhinitis in childhood is closely associated with asthma and should be considered a unified airway disease requiring integrated management. Recent Allergic Rhinitis and its Impact on Asthma and Korean Academy of Asthma, Allergy and Clinical Immunology guidelines advocate an evidence-based control-oriented stepwise treatment strategy that incorporates a patient-centered approach that is supported by both randomized trial data and real-world evidence. Intranasal corticosteroids (INCS) remain the first-line treatment for moderate to severe pediatric allergic rhinitis, whereas INCS plus intranasal antihistamine (INAH) combination therapy is recommended when symptom control is inadequate with INCS alone. Oral antihistamines (OAH) and INAH are recommended for children with mild disease or when rapid symptom relief is required. However, the addition of OAH to INCS therapy does not confer clinically meaningful additional benefits compared with INCS monotherapy in most patients with allergic rhinitis; therefore, routine combination therapy is not recommended. Leukotriene receptor antagonists are not recommended as first-line therapy for allergic rhinitis and are mainly used as add-on therapy in patients with concomitant asthma. In patients with predictable seasonal allergic rhinitis, INCS may be initiated 1-2 weeks before the anticipated pollen season to optimize symptom control. Pediatric management requires special consideration of age-specific clinical features, treatment adherence, safety, and caregiver education. The early diagnosis and guideline-based treatment of allergic rhinitis in children may improve their quality of life and reduce long-term respiratory morbidity.
Dietary fiber plays a central role in pediatric gastrointestinal health; however, most children worldwide consume amounts well below recommended levels. Current pediatric guidelines from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (2014) and global nutrition guidance from the World Health Organization recommend adequate dietary fiber intake as part of a balanced diet to support digestive health and prevent noncommunicable diseases. These recommendations generally correspond to daily fiber intake levels of approximately 14-31 g/day, or the practical rule of age (years) + 5 g/day for children, yet more than 80%-90% of children fail to meet these targets. This shortfall is clinically significant, as inadequate fiber intake is associated with increased risk of functional constipation, a condition affecting approximately 3%-29% of children globally. Dietary fiber contributes not only to stool bulk but also to the modulation of gut microbiota, gastrointestinal barrier function, and immune and metabolic pathways during critical developmental stages. Among common pediatric gastrointestinal disorders, the strongest evidence supports fiber use in constipation management, where supplementation or increased intake through whole foods has been shown to improve stool frequency and consistency in approximately 50%-60% of affected children. However, clinical trial outcomes remain inconsistent, varying according to fiber type, dosage, duration of intervention, and diagnostic criteria. Evidence for recurrent or functional abdominal pain remains limited and heterogeneous, with small sample sizes, differing endpoints, and high placebo response rates complicating interpretation. In pediatric inflammatory bowel disease, fermentable fibers have been shown to enhance short-chain fatty acid production. Nevertheless, robust pediatric clinical evidence remains insufficient, and findings from adult ulcerative colitis studies cannot be directly extrapolated to children. Dietary fiber represents an important supportive component of pediatric gastrointestinal management, but standardized dosing recommendations and high-quality pediatric clinical trials are still needed to establish evidence-based guidelines for clinical practice.
Background: Abnormal liver function tests (LFTs) are frequently performed in Emergency Departments (EDs); however, the systematic characterization of age-dependent clinical phenotypes and pathogen associations remains limited.Purpose: Here we aimed to identify the distinct clinical presentations and pathogen-specific associations of pediatric and adult ED visits for abnormal LFTs.Methods: This retrospective cohort study analyzed 26,874 ED visits for abnormal LFTs in South Korea's National Emergency Department Information System (2019–2023). Patients were stratified into pediatric (0–18 years) and adult (19–64 years) groups. We characterized the clinical presentations, concurrent diagnoses, temporal correlations with infectious pathogens, and metabolic comorbidity patterns.Results: The ED visits included 3,152 pediatric (11.7%) and 23,722 adult patients (88.3%). Pediatric presentations demonstrated fever-predominant profiles (47.3%), respiratory symptoms (6.4%), and infectious disease diagnoses (39.8%) as well as temporal correlations with respiratory viruses (rhinovirus, r=0.30; adenovirus, r=0.28; P<0.001). Adult presentations revealed previously unreported population-level temporal associations with enteric pathogens, including astrovirus (r=0.35), sapovirus (r=0.32), enteropathogenic Escherichia coli (r=0.38), and enterotoxigenic Escherichia coli (r=0.36, all P<0.001) coupled with infectious gastroenteritis (20.9%) and upper gastrointestinal disorders, including gastritis (18.3%). Adults demonstrated clustering of the following metabolic comorbidities: dyslipidemia (7.9%), hypertension (7.8%), and diabetes (6.0%). During the coronavirus disease 2019 pandemic, pediatric visits remained stable, whereas adult visits increased following the implementation of social distancing measures (rate ratio, 0.82; P=0.004).Conclusion: The ED presentation of abnormal LFTs results demonstrated distinct age-dependent phenotypes with divergent temporal pathogen associations. Pediatric cases reflected acute respiratory viral infections, whereas adult presentations showed novel population-level enteric pathogen associations with upper gastrointestinal disorders and clusters of metabolic comorbidities. These findings provide evidence supporting age-stratified diagnostic approaches for EDs.
Background: The impact of metabolic acidosis on short-term outcomes and mortality in very low birth weight infants (VLBWIs) has not been well studied.Purpose: To investigate the potential association between metabolic acidosis and the clinical outcomes of VLBWIs in South Korea.Methods: Between 2013 and 2019, data were collected from the Korean Neonatal Network, which covers a multicenter birth cohort spanning 75 hospitals. Our study cohort included 14,519 infants with a birth weight of less than 1,500 g who were admitted to the neonatal intensive care unit. Blood gas measurements taken within 1 hour of birth were used to evaluate the clinical outcomes, which were categorized into 5 groups according to base excess (BE) levels. We assessed respiratory outcomes, neurological morbidities, and infection-related and gastrointestinal outcomes along with mortality rates.Results: We analyzed 10,394 VLBWIs based on the inclusion criteria. A BE level below -9 suggested a significantly high risk of various respiratory outcomes, including air leak syndrome (adjusted odds ratio [aOR], 2.071; 95% confidence interval [CI], 1.305–3.285), massive pulmonary hemorrhage (aOR, 2.317; 95% CI, 1.502–3.575), pulmonary hypertension (aOR, 2.296; 95% CI, 1.667–3.161), and neonatal respiratory distress syndrome (aOR, 2.219; 95% CI, 1.778–2.769). These infants also exhibited an elevated risk of neurological (aOR, 2.797; 95% CI, 2.314–3.380), infection-related (aOR, 2.082; 95% CI, 1.653–2.623), gastrointestinal (aOR, 1.979; 95% CI, 1.408–2.783), and mortality (aOR, 2.683; 95% CI, 2.076–3.466) outcomes.Conclusion: Our findings highlight the potential effect of metabolic acidosis at birth on the clinical outcomes of VLBWIs. A strong correlation was observed between metabolic acidosis and neurological morbidity. These findings offer important insights for managing VLBWIs with metabolic acidosis and suggest the need for future research on acid-base balance risk factors.
Background:Neonates born small for gestational age (SGA) are at an increased risk of multiple severe complications, including infections. This suggests that immune cells and other peripheral blood cells may be affected. Purpose:Here we aimed to investigate whether SGA severity affects complete blood count and leukocyte differentiation of preterm neonates with a gestational age (GA) of <35 weeks and identify clinical factors that influence cell counts. Methods:This retrospective cohort study investigated the complete blood count sampled within 72 hours after birth in 1,940 preterm neonates admitted to the neonatal intensive care unit of Leiden University Medical Center. The neonates were divided into extreme SGA (<3rd birth weight percentile), moderate SGA (>3rd to <10th birth weight percentile), and controls (>10th birth weight percentile). Results:After multivariate analysis, extremely SGA neonates showed significantly decreased neutrophil, monocyte, lymphocyte, and thrombocyte counts. Thrombocyte counts were significantly lower in moderately SGA neonates than controls. In contrast, SGA status had no significant effect on erythrocyte count or hemoglobin concentration. Conclusion:Blood cell counts of extremely SGA neonates were decreased, mainly in the white blood cell line. The mechanisms underlying these decreased counts in SGA infants, especially their clinical effects, remain unclear.
