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Example of statements in published articles: https://actr.amegroups.org/article/view/8875; https://med.amegroups.org/article/view/8358/html. Contact with Editorial Office Mira Wu, Corresponding Editor, Translational Pediatrics Email: editor@thetp.org Publisher Information TP is published by AME Publishing Company. Address: Hong Kong branch office: Flat/RM C 16F, Kings Wing Plaza 1, NO. 3 on Kwan Street, Shatin, NT, Hong Kong, China. Updated on July 10, 2026
Navepegritide in children with achondroplasia
The persistent challenge of perioperative transfusions and the hidden threat of overtransfusion in pediatric surgery
Development and validation of a SEER-based auxiliary nomogram for clinical features associated with pulmonary metastasis status in pediatric osteosarcoma
Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Pulmonary metastasis is a severe metastatic manifestation of pediatric osteosarcoma and is strongly associated with poor prognosis. Identifying clinical features associated with pulmonary metastasis may help improve risk stratification and individualized clinical management. This study aimed to identify clinical features associated with pulmonary metastasis status at initial diagnosis in pediatric osteosarcoma and to develop and internally validate an auxiliary nomogram using data from the Surveillance, Epidemiology, and End Results (SEER) database for clinical risk stratification. Methods: Clinicopathological and treatment-related data of pediatric osteosarcoma patients diagnosed from 2004 to 2018 were extracted from the SEER database. Pulmonary metastasis status recorded at initial diagnosis was used as the outcome. Patients were randomly divided into training and validation cohorts. Variables associated with pulmonary metastasis were identified using univariate and multivariate logistic regression analyses, and a SEER-based auxiliary risk-stratification nomogram was constructed. Surgery and radiotherapy were interpreted as treatment-pattern variables rather than causal or pre-diagnostic predictors. Model performance was evaluated using calibration curves, the concordance index (C-index), receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: There were 1,362 pediatric patients randomly divided into the training cohort (n=965) and validation cohort (n=397). In the training cohort, multivariate logistic regression analysis identified four variables independently associated with pulmonary metastasis status, including T stage, N stage, surgery, and radiotherapy. A SEER-based auxiliary nomogram was constructed to identify clinical features associated with pulmonary metastasis status and to support risk stratification in pediatric osteosarcoma. The C-index values were 0.699 and 0.736 in the training and validation cohorts, respectively. The area under the ROC curve (AUC) values of the training and validation cohorts indicated acceptable discriminatory ability. Conclusions: This study developed a SEER-based auxiliary nomogram for identifying clinical features associated with pulmonary metastasis in pediatric osteosarcoma. Surgery and radiotherapy should be interpreted as treatment-pattern variables rather than causal or pre-diagnostic predictors. Further prospective studies incorporating imaging, pathological, molecular, and treatment-timing data are needed to validate and refine this model.
Global, regional, and national burden and changing trends of hepatoblastoma and retinoblastoma from 1990 to 2021, and projections until 2050: findings from the Global Burden of Disease Study 2021
Background: Hepatoblastoma and retinoblastoma, two common extracranial embryonal tumors, are the most prevalent primary cancer of liver and eye in childhood, respectively. Despite high survival in high-income regions, outcomes remain extremely poor in low-income regions, underscoring global health inequities and the need for evidence-based resource allocation. To address this gap, we explored the global, regional, and national burden of the two diseases from 1990 to 2021 and projected trends until 2050. Methods: We extracted data on incidence, prevalence, deaths, and disability-adjusted life-years (DALYs) of hepatoblastoma and retinoblastoma by age, sex, region, and country from the Global Burden of Disease (GBD) 2021 database. Age-standardised rates (ASRs) with 95% uncertainty intervals (UIs) and estimated annual percentage changes (EAPCs) were calculated to measure disease burden and trends. Spearman correlation analysis was applied to evaluate the association between the socio-demographic index (SDI) and disease burden. The Bayesian age-period-cohort (BAPC) model was utilized for projections. Results: From 1990 to 2021, ASRs of incidence, prevalence, deaths, and DALYs of hepatoblastoma decreased significantly (EAPCs: −2.03, −1.84, −2.54, −2.53, respectively). For retinoblastoma, the ASRs of incidence and prevalence first increased until 2019 and then decreased, yet exhibited overall upward trends (EAPCs: 1.35 for incidence, 1.36 for prevalence). However, the deaths and DALYs of retinoblastoma went downward. The combined burden of both cancers also declined from 1990 to 2021. Disease burden peaked at age 0–6 days for hepatoblastoma, and at 0–6 days and 2–4 years for retinoblastoma. In low SDI regions, ASRs of deaths and DALYs of retinoblastoma were higher than those of hepatoblastoma. V-shaped associations were seen between SDI and both ASRs of incidence and prevalence of hepatoblastoma (incidence: r=−0.241, prevalence: r=−0.159) and retinoblastoma (incidence: r=0.221, prevalence: r=0.224) from 1990 to 2021. The deaths and DALYs of both cancers declined with increasing SDI. Positive correlation was found between SDI and EAPCs of ASRs of hepatoblastoma and retinoblastoma from 1990 to 2021 (all r>0), except for those of retinoblastoma deaths and DALYs which were negatively correlated with SDI (deaths: r=−0.282, DALYs: r=−0.192). Projections suggested hepatoblastoma burden would decline globally but rise in America, while retinoblastoma incidence and prevalence would increase globally. Conclusions: Despite decreased global burden of hepatoblastoma, retinoblastoma incidence and prevalence increased. Besides, substantial age-related, regional and socioeconomic disparities existed. Predictions showed decreasing hepatoblastoma burden, but rising retinoblastoma cases. Targeted strategies are needed, especially in low SDI regions, including antenatal examination, early screening, genetic counseling, environmental and nutritional improvements, and international collaboration to strengthen healthcare training, referral networks, and multidisciplinary consultation to reduce disparities and promote children health.
Effects of leuprorelin acetate microspheres on sex hormones, secondary sexual characteristics, and predicted adult height in early and fast puberty girls: a real-world, single-arm, retrospective cohort study
Background: Gonadotropin releasing hormone analogs (GnRHa) are recommended for both central precocious puberty (CPP) and early and fast puberty, but their benefit on final adult height in later onset cases remains controversial. Boennuokang® leuprorelin acetate microspheres, the first domestic generic formulation, have been approved for CPP, but evidence in early and fast puberty girls is still limited. Considering the complexity of clinical management in early and fast puberty, more real-world studies are needed. Therefore, this study aimed to explore the effect of Boennuokang® leuprorelin acetate microspheres on hypothalamic-pituitary-gonadal (HPG) axis and predicted adult height (PAH) in early and fast puberty girls. Methods: This real-world, single-arm, retrospective cohort study consecutively enrolled 198 early and fast puberty girls treated with Boennuokang® leuprorelin acetate microspheres at The First Bethune Hospital of Jilin University between January 2022 and November 2023. Early and fast puberty was defined as pubertal onset after the diagnostic age cutoff for CPP, accompanied by progression to the next Tanner stage within 6 months and bone age (BA) advancement exceeding chronological age (CA) progression. Baseline variables were collected from the electronic medical record. Tanner stage was assessed by pediatric endocrinologists, sex hormones were measured using standardized biochemical assays, uterine length was evaluated by pelvic ultrasonography, BA was assessed using the Greulich Pyle method, and PAH was calculated using the Bayley-Pinneau method. Follow-up assessments were performed at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3), and 18 (T4) months. Longitudinal changes were analyzed using repeated measures analysis of variance (ANOVA) or Friedman tests. Results: The mean CA and BA of girls were 9.73±0.99 and 12.08±0.82 years, respectively. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol decreased after 18 months of treatment (all P<0.001). Specifically, the median [quartile 1 (Q1)–quartile 3 (Q3)] LH decreased from 2.7 (2.23–3.51) mIU/mL at T0 to 0.66 (0.48–1.22) mIU/mL at T4; the median (Q1–Q3) FSH decreased from 5.27 (4.82–6.10) mIU/mL at T0 to 2.00 (1.56–2.42) mIU/mL at T4; the median estradiol decreased from 163.50 (129.00–195.00) pmol/L at T0 to 36.70 (36.70–36.70) pmol/L at T4. Of note, the proportions of girls in the Tanner stage B5 exhibited a decreasing trend over time. The length of uterus decreased after 18 months of treatment (P<0.001). BA/CA ratio (P<0.001) and growth velocity (P=0.002) decreased over time. PAH increased, and loss in growth potential [genetic target height (GTH) minus PAH] decreased over time (both P<0.001). Body mass index initially increased after 3 months of treatment, then showed a reducing trend until month 18 (P=0.005). Conclusions: Boennuokang® leuprorelin acetate microspheres are associated with suppression of the HPG axis and increased PAH in early and fast puberty girls.
Global trends, projections, and inequalities in neonatal sudden infant death syndrome mortality attributable to risk factors from 1990 to 2021
Background: Sudden infant death syndrome (SIDS) remains a leading cause of infant mortality. The neonatal period, as a distinct stage within infancy, has been a focus due to its associated mortality burden. We evaluated the global mortality burden and temporal trends of neonatal SIDS attributable to each risk factor from 1990 to 2021, assessed socioeconomic inequalities across these risk factors, and projected these trends through 2035. Methods: Data on neonatal SIDS deaths and the proportions attributable to risk factors were obtained from the Global Burden of Disease (GBD) 2021 study. Temporal trends in mortality rates were assessed using the average annual percent change (AAPC), socioeconomic inequalities were evaluated using the slope index of inequality (SII) and the concentration index, and future mortality burden through 2035 was projected using autoregressive integrated moving average (ARIMA) models. Results: Behavioral risks, child and maternal malnutrition, and low birth weight and short gestation were the leading contributors to neonatal SIDS mortality, with the burden concentrated in lower sociodemographic index (SDI) regions. Between 1990 and 2021, mortality attributable to these risk factors declined globally but remained unevenly distributed across socioeconomic groups. Inequality analyses indicated a persistent concentration of deaths in disadvantaged settings. Projections to 2035 suggest continued declines for most risk factors, although environmental risks may decrease more slowly. Conclusions: SIDS in the neonatal period remains a major global health challenge, particularly in low-SDI regions. Interventions targeting behavioral risks, child and maternal malnutrition, and low birth weight and short gestation are urgently needed.
Correlation of body mass index and serum 25-hydroxyvitamin D levels with advanced bone age in children from northwest China: a cross-sectional study
Background: The relationship between advanced bone age (BA), obesity, and vitamin D status remains understudied in preschool Asian children, particularly in economically developing regions. This study examined the associations of overweight/obesity and vitamin D deficiency with advanced BA among children in northwest China. Methods: A cross-sectional study was conducted involving 1,462 children aged 3–12 years who underwent physical examinations at Gansu Provincial Maternity and Child-Care Hospital (February 2019–October 2023). BA was assessed via left wrist X-ray using the Tanner-Whitehouse 3 (TW3) RUS (radius, ulna, and short bones) method, with inter-rater reliability verified by an intraclass correlation coefficient (ICC) of 0.92 (discrepancies resolved by a third senior pediatrician). Serum 25-hydroxyvitamin D [25(OH)D] was measured using electrochemical luminescence immunoassay [Cobas e601, Roche Diagnostics; detection range: 3–100 ng/mL; intra-batch coefficient of variation (CV) <3%; inter-batch CV <5%]. Advanced BA was defined as the difference between BA and chronological age (CA) (BA-CA; BA minus CA) >1 year. The definition of advanced BA as BA-CA >1 year is widely adopted in clinical pediatric practice in China. Results: The prevalence of advanced BA was 7.9%, with significantly higher rates in girls (11.9% vs. 3.4% in boys, P<0.001), children aged 9–12 years (19.4%), and those with overweight (17.1%) or obesity (16.9%) compared to normal weight children (5.8%, P<0.001). Body mass index (BMI) was positively correlated with advanced BA (Spearman ρ=0.361, P<0.001) and exhibited moderate predictive value for advanced BA [area under the curve (AUC) =0.735; 95% confidence interval (CI): 0.684–0.786]. Overweight and obesity were associated with increased odds of advanced BA after adjustment for age and sex [overweight: odds ratio (OR) =2.49, 95% CI: 1.435–4.314, P<0.05; obesity: OR =2.33, 95% CI: 1.463–3.71, P<0.001], whereas serum 25(OH)D levels showed no significant association. Conclusions: Overweight and obesity were significantly associated with advanced BA in this cross-sectional cohort of children from northwest China, whereas no significant association was detected between serum 25(OH)D and advanced BA. These findings highlight the importance of nutritional monitoring for healthy skeletal development in economically transitioning regions.
Clinical characteristics and risk factors for severe pertussis in infants aged less than 3 months
Background: Pertussis is a globally prevalent infectious disease caused by Bordetella pertussis. Although extensive research has examined pertussis in children, studies specifically focusing on infants aged less than 3 months remain limited. The aim of this study was to analyze the clinical characteristics of pertussis and the risk factors associated with severe pertussis in infants aged less than 3 months. Methods: Clinical data from infants aged less than 3 months who were hospitalized with pertussis were retrospectively analyzed. Multivariate logistic regression analysis was conducted to determine risk factors for severe pertussis. Results: This study included 205 infants aged <3 months with pertussis who were hospitalized at a provincial‑level tertiary referral center for pediatric infectious diseases in Anhui, China, between July 2021 and August 2025. The median age at disease onset was 59.0 [interquartile range (IQR), 40.5–73.0] days. Among 205 infants, the incidence of severe disease was 13.2% (27 cases). Compared with the non-severe group, the severe group demonstrated statistically significant differences in the presence of cyanotic episodes, whooping cough, fever, maximum white blood cell (WBC) count >30×109/L, and concurrent pulmonary consolidation (χ2=20.523, 5.52, 8.376, 35.194, and 21.446; all P<0.05). Multivariate logistic regression analysis indicated that fever [odds ratio (OR) =6.874, 95% confidence interval (CI): 2.155–21.931], whooping cough (OR =0.155, 95% CI: 0.032–0.764), cyanotic episodes (OR =18.82, 95% CI: 4.013–88.252), maximum WBC count >30×109/L (OR =15.755, 95% CI: 1.650–150.437), and pulmonary consolidation (OR =7.772, 95% CI: 1.376–43.908) were independently associated with severe pertussis. Conclusions: In infants aged less than 3 months with pertussis, the incidence of severe disease is 13.2% in this cohort. Fever, cyanotic episodes, a maximum WBC count >30×109/L, and pulmonary consolidation are independently associated with an increased risk of severe pertussis, whereas whooping cough is associated with a lower risk of severe disease.
A single tertiary hospital-based retrospective observational study on epidemiological features and clinical correlates of severe pediatric Chlamydia pneumoniae pneumonia in post-pandemic in Shanghai
Background: Chlamydia pneumoniae pneumonia (CPP) is a common respiratory disease in children after the coronavirus disease 2019 (COVID-19) pandemic. Some may develop severe complications and augment the health burden on children. This study aims to analyze the epidemiological and clinical characteristics of children with CPP and explored the associated factors for severe Chlamydia pneumoniae pneumonia (SCPP). Methods: Based on the diagnostic criteria of severe community-acquired pneumonia (CAP) defined by the 2024 revised Guidelines for the management of CAP in children, we consecutively enrolled hospitalized children with CPP from January 2022 to December 2025. We retrospectively collected the clinical data of 121 children diagnosed with CPP and divided them into severe and non-severe groups. Univariate analysis was performed to explore the potentially relevant indicators associated with SCPP occurrence. Subsequently, meaningful indicators were subjected to multivariate logistic regression analysis to screen for independent clinical correlates for SCPP. Results: A total of 6,137 hospitalized children were enrolled in this study, among whom 121 cases were diagnosed with CPP, with a total positive rate of 1.97%. The proportion of CPP among the total hospitalized showed a significant annual increasing trend (rising from 1.53% to 6.81%). The significant difference was observed among different seasons (χ2=3.516, P=0.06). Comparisons between different genders showed no statistical difference. The mean age of CPP children was 9.67±3.32 years, with the highest incidence observed in 12–14 years (positive rate:14.23%). The main clinical manifestations were paroxysmal cough and fever. Besides, pulmonary and extrapulmonary complications occurred in 32 cases (26.45%) and 13 cases (10.74%) respectively; and 79 samples were found positive detection of other pathogens. Multivariate analysis indicated that neutrophil percentage (N%) [odds ratio (OR) =1.066, P=0.02], complement 4 (C4) (OR =1,251.898, P=0.03), immunoglobulin E (IgE) (OR =1.001, P=0.03), and the imaging findings predominantly characterized by consolidation (OR =31.106, P=0.03) are the independent clinical correlates for SCPP in children. Conclusions: Following the COVID-19 pandemic, the overall incidence of CPP among children in Shanghai remained at a relatively low level, but it exhibited a clear annual increasing trend with the highest prevalence occurred in spring and school-aged children that aged 12–14 years were particularly susceptible. The majority of symptoms were fever and cough. CPP is also prone to concurrent infections with other pathogens, and a higher proportion of severe cases were observed. In children with CPP, N% >57.45%, C4 >0.28 g/L, IgE >102.40 IU/mL, and the imaging changes predominantly manifested as pulmonary consolidation may be the critical condition alerts of SCPP.
Systemic immune-inflammation index as a risk factor for acute kidney injury in patients with neonatal jaundice
Background: Acute kidney injury (AKI) is a serious complication in patients with neonatal jaundice, and inflammation is key to its development. The systemic immune-inflammation index (SII) has been associated with AKI in adults, but its role in jaundiced neonates is unknown. This study aimed to assess the association between SII and AKI risk in this population. Methods: This retrospective study utilized data from the Medical Information Mart for Intensive Care-IV database, including 2,326 patients with neonatal jaundice. Due to skewed SII distribution, log2-transformed SII (logSII) was used. Logistic regression was used to analyze the logSII-AKI association. Restricted cubic spline (RCS) analysis was used to explore the nonlinear relationship. Subgroup and interaction analyses were conducted to assess the sensitivity of the relationship across clinical characteristics. Complete-case analysis and the E-value were used to assess the robustness of the association. The correlation between logSII and neonatal intensive care unit (NICU) duration was examined using Spearman correlation analysis. Results: Higher logSII was independently associated with increased AKI risk {adjusted odds ratio (OR) [95% confidence interval (CI)]: 1.230 (1.107, 1.369); P<0.001}. RCS analysis showed no significant departure from linearity (P for overall <0.001, P for non-linear =0.51), which remained robust after adjustment. The association was generally consistent across predefined subgroups (all P for interaction >0.05). The findings were robust in sensitivity analyses [E-value =1.76 for the point estimate; multiple imputation for bilirubin: OR 1.227 (1.105, 1.364); complete-case analysis: OR 1.256 (1.103, 1.431)]. Interestingly, higher logSII correlated with shorter NICU duration (Spearman r=−0.174, P<0.001). Conclusions: logSII demonstrates an independent, approximately linear association with AKI risk in jaundiced neonates. The paradoxical association with NICU duration warrants further investigation.
Development and internal validation of an XGBoost-based prognostic prediction model and risk stratification system for overall survival in pediatric neuroblastoma: a SEER-based study
Background: Neuroblastoma (NB) is a highly heterogeneous pediatric malignancy with markedly variable clinical outcomes. Although established risk classification systems provide important prognostic information, individualized survival prediction remains challenging. This study aimed to develop and internally validate machine learning-based prognostic models for overall survival (OS) in pediatric NB patients and to establish a risk stratification system based on the best-performing model. Methods: Data from 2,427 pediatric patients diagnosed with NB between 2000 and 2021 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible patients were randomly assigned to a training cohort (80%) and an internal validation cohort (20%). Least absolute shrinkage and selection operator (LASSO) regression identified six prognostic factors, including age, primary tumor site, tumor size, distant metastasis, SEER stage, and chemotherapy status. Six machine learning algorithms, including extreme gradient boosting (XGBoost), logistic regression, support vector machine, random forest, k-nearest neighbors, and decision tree, were developed to predict 1-, 3-, and 5-year OS. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), concordance index (C-index), and Brier score. Results: Among the six models evaluated, XGBoost demonstrated the best predictive performance in both the training and internal validation cohorts. In the validation cohort, the AUCs for predicting 1-, 3-, and 5-year OS were 0.767, 0.796, and 0.807, respectively. The C-index of the XGBoost model was 0.784 [95% confidence interval (CI): 0.746–0.821]. Metastatic status was identified as the most influential predictor. Based on XGBoost-derived risk scores, patients were successfully stratified into low-, intermediate-, and high-risk groups with significantly different survival outcomes (all P<0.05). Conclusions: An XGBoost-based prognostic model demonstrated favorable performance for individualized survival prediction in pediatric NB and enabled effective risk stratification using routinely available clinical variables. This model may complement existing prognostic assessment approaches; however, further external validation is required before clinical implementation.
A m6A/m1A/m5C-related eight-gene signature predicts prognosis and correlates with immune microenvironment in pediatric acute myeloid leukemia
Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyl-adenosine (m1A) are among predominate forms of RNA methylations implicated in the progression of cancer. The study aims to dissect the associations of m6A/m1A/m5C genes with survival, tumor microenvironment (TME) and predicted immunotherapy response in pediatric patients with acute myeloid leukemia (AML). Methods: RNA sequencing (RNA-seq) data were downloaded from Xena database. Differentially expressed m6A/m1A/m5C genes were filtered between dead and alive samples. Least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to identify optimal prognostic genes and construct a risk-score model. TME characteristics and immunotherapy response were analyzed across different risk subgroups. Results: Twenty-five differentially expressed m6A/m1A/m5C genes were identified. Eight optimal prognostic genes were selected via LASSO and an 8-gene-based prognostic model was built. It effectively distinguished high- from low-risk patients [survival difference: P value =6.328e−07, area under the curve (AUC) value =0.861 (0.820, 0.778)], with valid verification in a validation dataset [survival difference: P value =2.677e−02, AUC value =0.774 (0.625, 0.833)]. The risk score was an independent prognostic factor and a composite nomogram could more accurately predict survival probability. Low-risk patients had significantly higher levels of monocytes and lower tumor purity compared to high-risk patients. A trend toward differential risk scores was observed between predicted immunotherapy responders and non-responders. ZC3H13, NSUN2, METTL16, TRMT10C and DNMT3B, and TRMT6 possessed stronger correlations with tumor purity. Conclusions: We propose an 8-gene prognostic signature related to m6A/m5C/m1A and a risk-score model for assessing prognosis in pediatric AML. These genes may serve as promising preliminary prognostic biomarkers and warrant further exploration as potential immunotherapy targets for pediatric AML, pending validation in larger-scale prospective cohorts.
Global research trends in heterotaxy syndrome with congenital heart defects: a 20-year bibliometric analysis (2006–2025)
Background: Heterotaxy syndrome (HS) is a rare and complex congenital disorder characterized by abnormal development of the left-right axis and heterogeneous cardiovascular malformations. HS is associated with substantial morbidity and mortality, posing significant clinical challenges. Despite surgical advances, global research trends in HS remain poorly characterized. This study aimed to systematically analyze the global research landscape of HS from 2006 to 2025 using bibliometric methods, identify emerging themes, and highlight areas of clinical relevance. Methods: Publications on HS published from 2006 to 2025 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analyses were performed using CiteSpace and VOSviewer to assess publication trends, collaboration networks, journal distributions, and research hotspots. Results: A total of 493 publications involving 2,548 authors from 184 journals were included. Overall, publication output increased over time, peaking in 2022. The United States was the leading contributor to research productivity. Harvard Medical School and Boston Children’s Hospital were the leading institutions. Anderson RH was identified as the most prolific author, whereas Cardiology in the Young was the most productive journal in this field. Keyword and co-citation analyses revealed a transition from anatomical classification and staged surgical palliation toward genetic mechanisms, prognostic assessment, and long-term outcome evaluation. Conclusions: HS research remains in an evolving stage of development. This study outlines emerging research directions and thematic trends as the first bibliometric analysis in this field. These findings provide clinicians and researchers with a clearer understanding of the current research landscape and may serve as a reference for future investigations aimed at improving the management and outcomes of patients with HS.
A nomogram model for early recognition of acute necrotizing encephalopathy: a retrospective study
Background: Acute necrotizing encephalopathy (ANE) is an infection-associated encephalopathy characterized by acute onset and poor prognosis. Currently, there is a lack of effective prediction models for its early identification. To address this gap, we developed and validated a nomogram model for the early identification of ANE in pediatric patients. Methods: This retrospective study analyzed children presenting with seizures or consciousness disorders following coronavirus disease 2019 (COVID-19) or influenza infection at Children’s Hospital of Soochow University between November 2021 and February 2024. The single-center patient data were stratified into ANE/non-ANE groups, and then randomly divided into training and validation cohorts at a 7:3 ratio for internal validation. Logistic and least absolute shrinkage and selection operator (LASSO) regression were used to identify risk factors for ANE, and a nomogram was subsequently developed. The model’s performance was validated using the area under the curve (AUC) and the area under the precision-recall curve (AUPRC), and further validated through calibration curve and decision curve analysis (DCA). Results: Altered consciousness, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) were independently associated with ANE development. A nomogram model incorporating these four factors demonstrated high predictive performance, with AUC values of 0.961 and 0.978, and AUPRC values of 0.792 and 0.809 in the training and validation cohorts, respectively. Calibration curves, DCA, and clinical impact curves further indicated the model’s accuracy in predicting ANE onset. Conclusions: Our nomogram model provides a novel tool for the early identification of children at high risk of ANE, assisting clinicians in formulating timely interventions to improve patient prognosis.
Association of bronchoalveolar lavage fluid caspase-4 with inflammatory responses in pediatric acute respiratory distress syndrome
Background: Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity in critically ill children. Although dysregulated inflammation is central to ARDS pathogenesis, the contribution of upstream inflammatory signaling pathways, particularly caspase-4-mediated responses, has not been fully characterized in pediatric populations. This study aimed to investigate bronchoalveolar lavage fluid (BALF) levels of caspase-4 and related inflammatory mediators in children with ARDS and to examine their associations with inflammatory responses and disease severity. Methods: This retrospective study included children aged 1 month to 14 years with ARDS. After applying predefined inclusion and exclusion criteria, 28 patients with ARDS were enrolled and classified as Gram-negative bacterial infection–associated ARDS (n=14) or virus-associated ARDS (n=14), along with a separate non-infectious control group (n=17). BALF samples were collected during clinically indicated bronchoscopy. Levels of caspase-4, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Correlation analyses were performed to assess associations between caspase-4 levels, cytokines, and clinical severity indicators. Results: BALF levels of caspase-4, IL-1β, IL-6, and TNF-α did not differ significantly among the three groups. However, caspase-4 levels were positively correlated with IL-1β (r=0.641, P<0.001), IL-6 (r=0.668, P<0.001), and TNF-α (r=0.375, P=0.038). Caspase-4 was also positively associated with D-dimer levels (r=0.433, P=0.031) and showed a modest association with oxygenation index-related measures. Conventional inflammatory markers did not demonstrate consistent associations with disease severity. Conclusions: BALF caspase-4 levels are closely associated with local inflammatory activity in pediatric ARDS (PARDS). Although no significant differences were observed among etiological groups, the correlations between caspase-4 and inflammatory cytokines suggest that caspase-4 may reflect the intensity of pulmonary inflammation rather than pathogen-specific mechanisms. These findings support its potential value as a biomarker for disease assessment in PARDS.
An interpretable machine learning model based on routine clinical indicators for early identification of obesity-related non-alcoholic fatty liver disease in children: a single-center retrospective study
Background: There is still a lack of a noninvasive, individualized tool to pre-screen children with obesity for the risk of non-alcoholic fatty liver disease (NAFLD) and to prioritize referral for confirmatory abdominal ultrasonography. In this study, we aimed to develop and interpret a machine learning (ML)-based model for predicting ultrasound-defined NAFLD risk among children with obesity using routine clinical and biochemical indicators. Methods: This single-center retrospective study included 439 obese children treated at Siyang Hospital between February 2021 and December 2025. Demographic, anthropometric, and routine laboratory indicators were collected, and ultrasound-defined NAFLD was used as the study outcome. Least absolute shrinkage and selection operator (LASSO) regression and the Boruta algorithm were applied to identify robust predictive features, and six ML models—logistic regression, decision tree, random forest, extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and support vector machine (SVM)—were developed and compared to determine the optimal model. Model performance was evaluated in the test set, and Shapley Additive exPlanations (SHAP) was used to interpret the final model. Results: A total of 439 obese children were included in the analysis, of whom 206 (46.9%) had ultrasound-defined NAFLD. Seven variables were selected to develop six ML models. Among these, the LightGBM model showed the best overall performance across multiple metrics, with comparable discrimination among the top models in the test set, with an area under the curve (AUC) of 0.870, accuracy of 0.823, precision of 0.828, sensitivity of 0.787, specificity of 0.855, and F1 score of 0.807. SHAP analysis further demonstrated that waist-to-height ratio contributed most to the model output, followed by body mass index (BMI), triglyceride-glucose index × waist circumference (TyG-WC), serum uric acid, and triglyceride-glucose index × body mass index (TyG-BMI). Conclusions: This study developed an interpretable ML-based model for predicting ultrasound-defined NAFLD risk in obese children using routine clinical and biochemical indicators. LightGBM showed the best overall predictive performance, with good calibration and potential clinical utility. It may serve as a noninvasive auxiliary tool to pre-screen children with obesity and prioritize referral for confirmatory abdominal ultrasonography, supporting early identification and risk assessment of ultrasound-defined NAFLD, although further multicenter prospective studies and external validation are still needed before broader clinical application.
Global trends and emerging research hotspots in Alport syndrome: a comprehensive bibliometric analysis (1961–2024)
Background: Alport syndrome is a hereditary kidney disorder with multisystem involvement. This study aims to explore global research trends, collaboration networks, and emerging hotspots in the field of Alport syndrome using a bibliometric approach. Methods: A comprehensive literature search was conducted in the Web of Science Core Collection (WoSCC) on January 15, 2025, covering publications from 1961 to 2025. Bibliometric analysis was performed using VOSviewer, CiteSpace, and the R package “bibliometrix”. Results: A total of 1,637 articles on Alport syndrome were identified, showing a steady annual growth rate of 1.09% across six decades. The United States was the leading contributor with 420 articles, followed by China (170 articles) and Japan (162 articles). University of Minnesota ranked first in publication output (72 publications) and collaboration strength, whereas University of Helsinki and Karolinska Institute showed high average citation impact. Tryggvason K was identified as the most influential author, with 5,750 citations and the highest h-index (30). The keyword analysis revealed three major thematic clusters: genetic and molecular mechanisms, clinical features and genotype-phenotype correlations, as well as animal models and pathophysiology. Recent citation bursts highlighted emerging topics such as “digenic inheritance” (2018–2024) and “guidelines” (2019–2022), reflecting the shift toward precision medicine and standardized clinical management in the field. Conclusions: This bibliometric analysis highlights the rapid growth and promising potential of Alport syndrome research. The findings demonstrate sustained growth in research output and increasing attention to genotype-informed research, guideline-related topics, and clinical management. These results may help identify collaboration opportunities and directions for future studies.
From autism to obesity and beyond: mapping global trends and gaps in pediatric gut microbiota interventions—a bibliometric analysis
Background: Pediatric gut microbiota interventions are increasingly applied in conditions such as autism spectrum disorder (ASD), obesity, and malnutrition; however, the global research structure and thematic trends remain unclear. This study aimed to map the global research landscape of pediatric gut microbiota interventions from 2010 to 2025, characterizing publication trends, geographic and institutional distribution, collaboration networks, and thematic evolution, in order to identify research hotspots and evidence gaps that should guide future priorities. Methods: Publications from January 1, 2010, to June 30, 2025, were retrieved from the Web of Science Core Collection (WoSCC) using predefined search terms. Microsoft Excel 2021, VOSviewer 1.6.19, CiteSpace 6.2.4, and the R package bibliometrix 4.0.0 were employed to analyze publication trends, geographic distribution, institutional and author collaborations, highly cited works, and keyword co-occurrence. Results: A total of 1,915 articles involving 12,308 authors across 546 journals were identified, citing 39,956 references and generating 3,510 unique keywords. Global output has increased markedly over 15 years, with China and the United States forming a “dual-core” dominance. Only 27.12% of the studies resulted from multi-country (international) collaborations, indicating limited cross-regional partnerships. Research hotspots have centered on ASD, obesity, and nutritional disorders, while developmental and behavioral outcomes have been underrepresented. Personalized nutrition, microbiota-brain-behavior links, and multi-omics integration have emerged as growing themes. Conclusions: This bibliometric study maps the global landscape of pediatric gut microbiota interventions, revealing rapid expansion but thematic imbalance. Greater multinational collaboration and broader inclusion of developmental health endpoints emerge as key priorities for the future research agenda.
Mapping the evolving landscape: a bibliometric analysis of macrophages research in bronchopulmonary dysplasia (1990–2025)—a Web of Science Core Collection-based study
Background: Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity, and macrophages are increasingly recognized as important drivers of lung injury and repair. We therefore performed a bibliometric analysis to map research trends, key contributors, and evolving hotspots in macrophage-related BPD research. Methods: We searched the Web of Science Core Collection (WoSCC) on December 5, 2025, using topic terms for BPD/ventilator-induced lung injury and macrophage-related keywords, and included English-language original research articles published from January 1990 to December 2025. VOSviewer, CiteSpace, and the R package bibliometrix were used to analyze publication trends, collaboration networks, keyword co-occurrence clusters, and burst keywords. Results: A total of 587 original research articles from 1990 to 2025 were included. Annual publications rose from fewer than 5 before 1995 to a peak of 30 in 2020, showing steady linear growth. The USA led in output (217 articles, 37.0%), followed by China (123, 21.0%) and Germany (45, 7.7%). The University of Toronto (104 articles) and Harvard University (78 articles) were the most productive institutions. The top journal was American Journal of Physiology-Lung Cellular and Molecular Physiology (70 articles, h-index =37). Leading authors included Li Li-Fu (11 articles) and Jankov Robert P. (10 articles). Keyword network and temporal analyses revealed a thematic shift from early emphasis on ventilator-associated injury and classical inflammatory mediators toward developmental biology, gene regulation, cellular heterogeneity, and pulmonary vascular disease, with recent bursts highlighting NF-κB signaling, pulmonary hypertension, inflammation, and BPD. Conclusions: Macrophage-related BPD research has shifted from early work on general inflammation and injury to more recent studies emphasizing gene regulation, signaling pathways, and pulmonary vascular complications. Key needs include stronger integration of human data with animal models, improved data standardization, and broader collaboration. Future studies should combine multi-omics with clinical outcomes to support immune-targeted and precision approaches for neonatal lung disease.
Effects of two securement methods on peripherally inserted central catheter stability and skin integrity in very low birth weight infants: a retrospective study
Background: Very low birth weight infants often require peripherally inserted central catheter (PICC) for long-term venous access. Conventional securement methods are associated with high rates of catheter dislodgement and skin injury, but the clinical effectiveness and cost-effectiveness of modified combination securement methods remain insufficiently validated. This study aimed to investigate the effects of a novel combination securement method on catheter dislodgement and skin injury in very low birth weight infants (VLBWIs) undergoing PICC placement, and to perform a cost-effectiveness analysis to inform evidence-based selection of the optimal securement strategy. Methods: This retrospective, single-center analysis comprised 181 VLBWIs who underwent PICC placement in the neonatal intensive care unit (NICU) between January 2018 and December 2025. Infants were assigned to either a conventional securement group (conventional group) or a modified combination fixation group (modified group), the latter consisting of four steps: pressure relief protection, tension-free fixation, buffer reinforcement, and sealing coverage (termed ‘protection-pressure reduction-fixation-sealing’). A 1:1 nearest-neighbor propensity score matching (PSM) approach was used to balance baseline confounders. After matching, clinical outcomes and direct medical costs were compared between groups, and correlations between cost metrics and clinical outcomes were analyzed. Results: Following matching, baseline characteristics were well balanced between groups, with no significant differences (all P>0.05). The modified group showed significantly lower rates of unplanned PICC removal and skin injury than the conventional group (P=0.02 and P<0.001, respectively). Logistic regression identified the modified securement method as an independent protective factor against unplanned PICC removal in VLBWIs [odds ratio (OR) =0.275, P=0.005]. Moreover, total direct medical cost per PICC placement was significantly lower in the modified group (P<0.001). Conclusions: The modified combination securement method significantly improves clinical outcomes associated with PICC placement in VLBWIs, reduces complication rates, and achieves overall cost savings. Offering both clinical and economic benefits, this approach warrants widespread adoption in the NICU.
Biochemical outcomes and safety profiles of compound glycyrrhizin versus magnesium isoglycyrrhizinate in Kawasaki disease: a retrospective propensity score‑matched cohort study
Background: Hepatic dysfunction is a common extra-cardiac manifestation of Kawasaki disease (KD). Compound glycyrrhizin (CG) and magnesium isoglycyrrhizinate (MgIG) are widely used hepatoprotective agents in Asian populations. However, no study has directly compared their efficacy and safety in pediatric KD patients with liver enzyme abnormalities. This study aims to compare the biochemical outcomes and safety profiles of CG versus MgIG in KD children with elevated liver enzymes, and to identify factors associated with treatment response. Methods: This retrospective cohort study included KD inpatients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 times the upper limit of normal (ULN) who received monotherapy with either CG or MgIG. Propensity score matching (PSM) at a 2:1 ratio was applied to balance baseline characteristics. Biochemical responses were assessed by the absolute changes in ALT and AST from baseline to 1 week, as well as by categorical responses (complete normalization and partial biochemical response). A multivariable logistic regression model was used to evaluate the independent association between treatment group and partial biochemical response, adjusting for gender, timing of treatment initiation, and intravenous immunoglobulin (IVIG) resistance. Safety profiles were also compared. Results: After PSM, 129 patients (CG: n=80; MgIG: n=49) were analyzed. Both treatments were associated with significant reductions in ALT and AST from baseline (all P<0.001), with no significant between‑group differences in absolute changes (ALT: P=0.07; AST: P=0.11). Partial biochemical response at 1 week was observed in 86.25% of CG patients and 69.39% of MgIG patients (P=0.02). However, after adjusting for gender, timing of treatment initiation, and IVIG resistance, treatment group was not independently associated with partial biochemical response [odds ratio (OR) =0.542, 95% confidence interval (CI): 0.203–1.452, P=0.22]. Each 1‑day delay in treatment initiation was associated with a 19% reduction in the odds of response, making it the only significant independent predictor. Adverse events were reported in 3.75% of CG patients and 4.08% of MgIG patients, with no serious events and no significant between‑group difference (P>0.99). Conclusions: In this retrospective PSM cohort study, both CG and MgIG were associated with significant biochemical improvements from baseline. After adjustment for confounders, no independent association was found between treatment group and partial biochemical response. Earlier initiation of hepatoprotective therapy was the only factor significantly associated with better biochemical outcomes.
Disease burden of pulmonary aspiration and foreign body in airway in Asian children: a review based on Global Burden of Disease data and projections for 2035
Background: Pulmonary aspiration and foreign bodies (PAFB) represent one of the most common pediatric emergencies. The condition shows a marked age-related distribution, with children under five years of age being particularly vulnerable. As the region with the largest pediatric population worldwide, Asia may bear a substantial burden of PAFB; however, large-scale, population-based studies remain scarce. This study aimed to assess the epidemiological burden of pediatric PAFB in Asia from 1990 to 2021 and to provide evidence-based insights for public health policymaking. Methods: Data were obtained from the Global Burden of Disease (GBD) 2021 database, covering incidence, mortality, and disability-adjusted life years (DALYs) related to PAFB among children aged 0–14 years across Asian countries. Descriptive statistical analyses were conducted to examine trends over time. Correlation analyses were performed to explore associations between the sociodemographic index (SDI) and disease burden. The Bayesian Age-Period-Cohort (BAPC) model was used to project future trends in countries including China, India, Japan, and South Korea. Results: In 2021, an estimated 353,768 new PAFB cases occurred among Asian children aged 0–14 years, with an incidence rate of 32.457 per 100,000. A total of 11,159 deaths were reported, corresponding to a mortality rate of 1.024 per 100,000. The burden in terms of DALYs reached 992,887, with a DALY rate of 91.094 per 100,000. Between 1990 and 2021, the estimated annual percentage change (EAPC) was −2.59% for incidence, −3.43% for mortality, and −3.44% for DALYs. Central Asia experienced the highest disease burden, while Southeast Asia had the lowest. A significant negative correlation was observed between the SDI and disease burden. Projections indicate a continued decline in PAFB burden in China, India, Japan, and South Korea through 2035. Conclusions: Over the past three decades, the burden of pediatric PAFB in Asia has significantly declined, though regional disparities persist, with Central Asia remaining the most affected. The strong inverse relationship between the SDI and PAFB burden underscores the importance of socioeconomic development, public health education, and emergency response systems. Projections based on the BAPC model suggest continued improvements in disease burden across the Asia-Pacific region in the coming years.
Association between preoperative 25-hydroxyvitamin D3 levels and postoperative delirium in pediatric patients undergoing general anesthesia for laparoscopic surgery: a single-center retrospective study
Background: Postoperative delirium (POD) is a common complication after pediatric general anesthesia, impairing recovery. While vitamin D deficiency (VDD) is linked to POD in adults, its role in children remains unclear. This study investigates the association between preoperative 25-hydroxyvitamin D3 [25(OH)D3] levels and POD in children undergoing laparoscopic surgery under general anesthesia. Methods: This single-center retrospective study enrolled 320 pediatric patients. Demographic, surgical, anesthetic, and laboratory data were collected. Preoperative serum 25(OH)D3 was measured, and POD was assessed using the Cornell Assessment of Pediatric Delirium (CAPD) scale on postoperative days 1, 3, and 7. Meanwhile, patients were categorized into VDD (<30 ng/mL) and non-VDD (≥30 ng/mL) groups. Multivariable logistic regression identified independent risk factors for POD. Results: The incidence of POD was 80.3% (257/320) based on the CAPD score ≥9. POD patients had significantly lower serum 25(OH)D3 levels (P<0.05). In multivariable analysis, preoperative VDD was independently associated with a significantly higher risk of POD [adjusted odds ratio (OR) =14.25; 95% confidence interval (CI): 3.33–61.0; P<0.001]. A sensitivity analysis incorporating postoperative sleep quality [Children’s Sleep Habits Questionnaire (CSHQ) score] confirmed the robustness of this association (OR =8.15; 95% CI: 1.88–35.3; P=0.005). The area under the receiver operating characteristic (ROC) curve for 25(OH)D3 in identifying POD was 0.613. Conclusions: Preoperative VDD is independently associated with a substantially increased risk of POD in pediatric patients undergoing general anesthesia for laparoscopic surgery. Preoperative screening for VDD may help identify at-risk children, and randomized controlled trials are warranted to evaluate whether preoperative vitamin D supplementation reduces POD incidence.
Effect of perioperative Sonoclot monitoring on early thrombosis after pediatric liver transplantation: a prospective observational study
Background: Postoperative thrombosis is the most serious and common complication for children. The Sonoclot device is used to monitor coagulation function in transplant patients. However, no Sonoclot-based threshold for identifying children at risk of thrombosis has been established. This study aimed to identify the Sonoclot parameter and its optimal cutoff value for predicting early postoperative thrombosis in pediatric living-donor liver transplantation. Methods: This was a single-center, prospective and observational study. The study was performed in Tianjin First Central Hospital, Tianjin, China, between September 2019 to May 2021. Clinical data of 200 children with living-donor liver transplantation (LDLT) were collected and observed. The effects of coagulation function monitoring by Sonoclot devices at 1 h after ischemia-reperfusion on early thrombosis were analyzed. Receiver operating characteristic (ROC) analysis was used to obtain the sensitivity and cutoff value of Sonoclot parameters for the diagnosis of thrombosis. Results: A total of 38 cases (19%) had thrombosis complications. Twenty-three cases (11.5%) had postoperative hepatic artery thrombosis and 15 cases (7.5%) had portal vein and hepatic vein thrombosis. Univariate and multivariate analyses showed that whole blood activated clotting time (ACT) was independent risk factor for early postoperative thrombosis. ROC analysis found that the area under the curve (AUC) of ACT for the diagnosis of postoperative thrombosis was 0.918 (95% confidence interval: 0.872–0.954), and the cutoff value to predict early postoperative thrombosis was 228.5 s. The lower-ACT group had a higher incidence of overall thrombosis and hepatic artery thrombosis. Conclusions: ACT after ischemia-reperfusion was a risk factor for early postoperative thrombosis. Maintaining ACT above 228.5 s was associated with a lower incidence of early thrombosis in this cohort. Prospective randomized studies are needed to confirm a causal therapeutic target.
Development of a parsimonious predictive model for height gain outcome in children with central precocious puberty following gonadotropin-releasing hormone agonist therapy
Background: Central precocious puberty (CPP) is associated with compromised adult height if untreated, and gonadotropin-releasing hormone agonist (GnRHa) therapy remains the standard treatment. However, height gain during treatment varies considerably among patients, and clinically practical tools for early identification of children at risk for suboptimal growth response are lacking. This study aimed to identify prognostic determinants of suboptimal height gain during GnRHa therapy and to develop a parsimonious predictive model to facilitate evidence-based clinical decision-making and optimal intervention timing. Methods: A retrospective cohort study was conducted enrolling children with CPP treated with triptorelin. Baseline clinical and biochemical parameters were collected, including chronological age, height standard deviation score (SDS), body mass index (BMI) SDS, insulin-like growth factor-1 (IGF-1) SDS, bone age advancement [bone age minus chronological age (BA-CA)], Tanner stage, GnRH-stimulated luteinizing hormone (LH) peak, and serum estradiol concentrations. Patients were stratified into favorable and unfavorable outcome cohorts based on height gain during treatment. Univariate and multivariable logistic regression analyses were performed to identify independent predictors. Three predictive models were constructed: M0 (comprehensive model with five predictors: IGF-1 SDS, BMI SDS, BA-CA, Tanner stage, and age), M1 (univariate model with IGF-1 SDS), and M2 (parsimonious model with IGF-1 SDS and BA-CA). Model performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA; 1–50% risk thresholds), and bootstrap internal validation. Results: A total of 163 children with CPP were enrolled (favorable outcome: n=113; unfavorable outcome: n=50). Multivariable logistic regression identified BMI SDS [odds ratio (OR) =2.33, 95% confidence interval (CI): 1.14–4.76, P=0.02], IGF-1 SDS (OR =1.94, 95% CI: 1.24–3.02, P=0.004), and bone age advancement (OR =21.49, 95% CI: 5.41–85.30, P<0.001) as independent predictors for unfavorable outcome. The area under the curve (AUC) was 0.838 (95% CI: 0.774–0.903) for M0, 0.664 (95% CI: 0.573–0.754) for M1, and 0.815 (95% CI: 0.748–0.883) for M2. DeLong test revealed no significant difference between M2 and M0 (ΔAUC =–0.023, P=0.24). Bootstrap internal validation (1,000 iterations) demonstrated optimism-corrected AUC values of 0.810, 0.661, and 0.807 for M0, M1, and M2, respectively. M2 exhibited optimal calibration slope (0.957, 95% CI: 0.642–1.389) closest to unity. Brier scores were 0.160 for M0 and 0.167 for M2. DCA demonstrated comparable clinical net benefit for M0 and M2 across 1–50% risk thresholds. Conclusions: The parsimonious model (M2) incorporating IGF-1 SDS and bone age advancement demonstrates robust predictive capability for height gain outcome in children with CPP receiving GnRHa therapy, comparable to the comprehensive model. This model may support early risk stratification and closer growth monitoring in selected patients; however, external validation and confirmation against final adult height outcomes are required before it can inform decisions about adjunctive interventions.
Predictive value of bronchoalveolar lavage fluid leukotriene C4 for airway hyperresponsiveness in children with Mycoplasma pneumoniae pneumonia: a machine learning-based study
Background: Airway hyperresponsiveness (AHR) is a frequent sequela after acute Mycoplasma pneumoniae pneumonia (MPP) in children. This study assessed the association between bronchoalveolar lavage fluid (BALF) leukotriene C4 (LTC4) and MPP, evaluated its predictive value for AHR, and developed an early-identification machine-learning model. Methods: We retrospectively studied 158 children with MPP admitted between January 2023 and December 2024; 20 children undergoing bronchoscopy for airway foreign bodies served as controls. BALF LTC4 was measured by enzyme-linked immunosorbent assay (ELISA). AHR was assessed in 87 patients at a 2-week follow-up (positivity 39.1%) using a composite of clinical and spirometric criteria rather than bronchial provocation testing. Features were selected by least absolute shrinkage and selection operator (LASSO) regression and recursive feature elimination (RFE). Nine machine-learning models, including a support vector classifier (SVC), were compared, and predictions were interpreted with SHapley Additive exPlanations (SHAP). Results: In the matched cohort, BALF LTC4 was higher in MPP than in age- and sex-matched controls (46.14 vs. 10.46 pg/mL, P<0.001). Baseline LTC4 was higher in AHR-positive than AHR-negative patients (80.91 vs. 39.92 pg/mL, P<0.001). LTC4 correlated negatively with follow-up lung function [forced expiratory volume in 1 second (FEV1) percent predicted, FEV1/forced vital capacity (FVC); Spearman’s rho =−0.44 to −0.48], whereas C-reactive protein (CRP) and interleukin-6 (IL-6) did not. An SVC using LTC4 and lactate dehydrogenase (LDH) performed best, with a leave-one-out cross-validation area under the curve (AUC) of 0.876 [95% confidence interval (CI): 0.791–0.943], accuracy 81.6%, sensitivity 73.5%, and specificity 86.8%. SHAP analysis indicated LTC4 was the stronger predictor, with a contribution approximately 1.92 times that of LDH. Conclusions: In this retrospective single-center cohort, BALF LTC4 was associated with post-MPP AHR in children and showed greater predictive value than systemic inflammatory markers. A parsimonious SVC based on BALF LTC4 and serum LDH showed encouraging performance, suggesting potential utility for early risk stratification. However, the 55% follow-up rate and selection toward clinically complex patients may have overestimated performance; prospective multicenter validation with more complete follow-up is warranted before clinical implementation.
Imaging and pathological features of pediatric sclerosing angiomatoid nodular transformation of the spleen: a case series and hypothesis-generating perspective on non-operative management
Background: Sclerosing angiomatoid nodular transformation (SANT) is a benign non-neoplastic splenic lesion, well described in adults but rarely reported in children. Its clinical and imaging features in pediatric patients remain poorly characterized, and the optimal management—surgical versus non-operative—is uncertain, especially given the risks of splenectomy in children (e.g., overwhelming post‑splenectomy infection). This case series of four pediatric patients aims to describe the imaging-pathology correlation of SANT and generate a hypothesis regarding potential non-operative management in selected cases. Case Description: Four male children (age range 36–156 months) presented with solid splenic masses and underwent partial splenectomy. All four had preoperative ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Postoperative pathology confirmed isolated splenic SANT in three patients; one patient had synchronous splenic SANT and a separate pancreatic calcifying fibrous tumor. Imaging features varied: the characteristic “spoke‑wheel” enhancement pattern was present in only two of four cases. MRI better delineated fibrous septa, hemosiderin deposition, and nodular boundaries than CT. All patients recovered uneventfully after surgery. Follow‑up ranged from 52 to 132 months, with no recurrence or metastasis. Conclusions: Pediatric splenic SANT should be considered in the differential diagnosis of a well-circumscribed solid splenic mass, even without the classic spoke-wheel sign. Because SANT is benign and splenectomy carries risks, a hypothesis-generating alternative is close observation after percutaneous core‑needle biopsy confirmation. However, this approach requires prospective validation; When imaging findings are atypical or malignancy cannot be excluded, surgical resection remains the definitive intervention, surgical resection remains the definitive intervention.
From pixels to precision: a narrative review of AI-driven 3D morphological analysis and digital twinning in alveolar cleft management
Background and Objective: Alveolar cleft is a congenital craniofacial anomaly of common occurrence and is frequently seen in cleft lip and palate patients. This condition affects the patient's chewing, speech, and psychological and social life. This review aims to offer a broad overview of the role of artificial intelligence (AI) throughout the entire management of an alveolar cleft from diagnosis to treatment and to life after surgery, in terms of quality of life. Methods: This is a narrative review, and the information was obtained from the literature and clinical guidelines. From the previous publications, we reviewed the advancements in the use of AI for the diagnosis, treatment, and management of alveolar clefts and other fields. Key Content and Findings: In the field of alveolar ridge defects, the applications of AI have been mainly used in combination with cone-beam computed tomography (CBCT). It accurately identifies the extent of the bone defect and calculates the volume of the bone defect from imaging. Moreover, AI can support personalized surgical planning and predict bone resorption and maxillofacial growth patterns. AI and CBCT are shifting the subjective, “experience-driven” qualitative assessment of alveolar clefts to an objective, “data-driven” evaluation that is multidimensional. Conclusions: AI holds significant potential for applications in 3D image analysis, quantitative evaluation, and surgical planning of alveolar clefts, but it is currently hindered by several challenges, such as limited generalizability of models, lack of interpretability, and privacy concerns. Solutions to these problems include advancing towards multicenter standardized databases, federated learning, and model efficiency. The future of alveolar cleft management is expected to be improved with the use of generative AI and digital twins throughout their lifespan, in a personalized way.
From homeostasis to dysregulation: human milk, microbial metabolites, and the preterm intestinal microenvironment in necrotizing enterocolitis
Preterm birth disrupts normal intestinal and immune development, leading to preterm neonates increased vulnerability to necrotizing enterocolitis (NEC). The immature gut is characterized by impaired epithelial barrier formation, altered intestinal epithelial cell function, and underdeveloped mucosal immune responses, all of which disrupt intestinal homeostasis. In addition, microbial colonization in preterm neonates differs substantially from that in term neonates, with reduced abundance of beneficial taxa, delayed establishment of a stable microbiota, and altered production of microbial metabolites. These early-life disturbances are closely associated with NEC pathogenesis. Human milk is increasingly recognized as more than a source of nutrition in preterm neonates. Its bioactive components contribute to intestinal protection by strengthening epithelial integrity, regulating immune responses, and limiting excessive inflammation. In parallel, human milk shapes gut microbial colonization and promotes the generation of functional microbial metabolites, which further influence barrier maturation and mucosal immune homeostasis. This review summarizes the ontogeny of the preterm gut, with a focus on epithelial and immune development, and discusses human milk-driven microbiota and their major metabolites in preterm neonates. It further highlights the mechanisms by which human milk bioactive components and microbiota-derived metabolites protect against NEC. Understanding the interplay among immature intestinal development, human milk, and microbial metabolism may provide new insights into NEC pathogenesis and support the development of targeted preventive strategies for preterm neonates.
Participation of children with obstructive sleep apnea in clinical trials: a systematic review of barriers and interventions
Background: Obstructive sleep apnea (OSA) has negative effects on neurocognitive development and metabolic health in children. Despite this, children with OSA remain underrepresented in research; consequently, most evidence on treatment is based on adult data. This review focuses on studies assessing barriers to clinical trial participation in children with OSA and discusses intervention studies and efforts to overcome these barriers. Methods: We retrieved articles from Scopus, Embase, PubMed, and the Cochrane Library without date restrictions until February 2026. The language used was restricted to English. The Joanna Briggs Institute (JBI) tool was used to assess methodological quality. Results: Of the 28 included studies, 14 barrier subcategories were identified across three domains: objective factors (25 studies), provider factors (6 studies), and patient/caregiver factors (25 studies). The most frequently reported barriers were stringent eligibility criteria, refusal of follow-up, treatment disagreement, and health problem. Conclusions: Our findings emphasize multifaceted barriers to enrolling children with OSA in clinical trials. Furthermore, we provided several underutilized solutions to facilitate children’s participation in clinical trials. However, formal targeted strategies are still needed in the future, because these recommendations alone might not solve the evidence gap in children.
Early recognition and bundle-based management of pediatric sepsis in the emergency department: a narrative review
Background and Objective: Pediatric sepsis is a high-stakes, time-sensitive emergency, yet early recognition in the emergency department (ED) remains inconsistent because presenting features are heterogeneous, early signs are nonspecific, and implementation capacity varies across hospitals. At the same time, evidence for bundle-based care has expanded, but important clinical questions remain regarding which recognition approaches are most reliable in frontline ED settings, which bundle elements are best supported, and why pathway uptake remains uneven. This narrative review was undertaken to address these questions and to clarify current evidence gaps relevant to pediatric emergency practice. Methods: This structured narrative review searched PubMed on March 15, 2026 for studies published from January 1, 2010 through March 15, 2026 using terms related to pediatric sepsis, emergency care, screening, early recognition, sepsis bundles, biomarkers, quality improvement, and digital decision support. We focused on ED-relevant studies addressing recognition strategies, bundle implementation, nursing or workflow processes, and emerging technologies. Titles and abstracts were screened against predefined inclusion and exclusion criteria, and the final literature set was synthesized thematically into recognition, management, implementation, and future-direction domains. No language filter was planned at search design, but the review was limited to studies with accessible English full-text data for analysis. Key Content and Findings: Current evidence supports a layered ED recognition model that combines clinical assessment with structured screening, targeted biomarkers, and workflow-integrated digital support rather than reliance on any single tool. Evidence is strongest for bundle pathways improving process outcomes such as time to antibiotics, pathway activation, and compliance with first-hour care targets. By contrast, evidence for direct mortality benefit, stand-alone biomarker superiority, and routine use of artificial intelligence (AI)-enabled systems remains promising but inconsistent because studies are heterogeneous in definitions, populations, and implementation context. The literature also shows that success in general ED practice depends heavily on pediatric readiness, nursing-led escalation, local workflow design, and multidisciplinary coordination. Conclusions: Pediatric sepsis care in the ED should be organized around rapid recognition plus measurable, context-adapted bundle delivery. The clearest evidence gaps involve external validation of recognition tools in general EDs, more explicit evaluation of individual bundle components, harmonized operational definitions and bundle metrics, and implementation studies that test how digital support and nursing workflows can improve frontline performance.
Multimodal strategies for alleviating postoperative pain in children: a narrative review on research progress and evidence-based practice
Background and Objective: Postoperative pain is a prevalent and clinically important issue in pediatric surgery. Poor pain control can hinder recovery, increase distress, and lead to negative short- and long-term outcomes. Due to developmental, physiological and behavioral differences between children and adults, pediatric pain management needs tailored strategies. This review aims to summarize recent evidence on multimodal pediatric postoperative pain management. Methods: A narrative review was conducted to synthesize updated evidence on multimodal analgesic approaches for children undergoing surgery. Literature from 2010 to 2025 was retrieved from PubMed using keywords: pediatric postoperative pain, multimodal analgesia, opioid-sparing care, non-pharmacologic intervention, family-centered care, evidence-based practice and digital health. The review was prepared in accordance with the Narrative Review reporting checklist. Key Content and Findings: Evidence supports non-opioid basic analgesics, regional techniques and standardized perioperative pathways for better pain control and less opioid use. Non-pharmacological and theory-guided interventions [distraction, virtual reality (VR), family engagement, caring nursing] further enhance pain relief and recovery. Future trends focus on implementable models integrating standardized assessment, individualized multimodal therapy, family participation and digital follow-up. Conclusions: Effective pediatric postoperative pain management relies on multidisciplinary cooperation throughout the perioperative period. Family‑centered multimodal strategies with ongoing pain monitoring are essential to reduce opioid‑related side‑effects and facilitate children’s holistic recovery.
CK-MM screening using neonatal dried blood spots may be inadequate at detecting all dystrophin mutation carriers
Response to: CK-MM screening using neonatal dried blood spots may be inadequate at detecting all dystrophin mutation carriers
A mono-organ POLG1-related mitochondrial DNA depletion syndrome must be confirmed by quantitative real-time polymerase chain reaction (PCR) or droplet digital PCR