Translational pediatrics最新文献

Background: Acute kidney injury (AKI) is a serious postoperative complication in hospitalized neonates. We aimed to develop and evaluate a machine learning (ML) model for predicting the risk of postoperative AKI in neonates.

Methods: The clinical records of 2,025 neonates were collected, and the patients were randomly divided into training and test sets. The outcome variable was the occurrence of postoperative AKI, and the models incorporated 25 predictive variables, including demographics, intraoperative infusions, and postoperative indicators. ML models were developed using six different algorithms on the training set, and their performance was assessed on the test set using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The model with the best AUC was selected for validation in the test set. The association between the risk factors and postoperative AKI was interpreted using the SHapley Additive exPlanations (SHAP) method.

Results: A total of 110 neonatal patients (5.43%) developed AKI following surgery. Patient age, operation duration, and urine output were the three most important predictors of AKI. Among the tested models, the logistic regression (LR) algorithm was the best predictor of postoperative AKI, achieving the highest AUC [median, 0.807; 95% confidence interval (CI): 0.701-0.897] and the highest sensitivity (median, 0.733; 95% CI: 0.5-0.938). The SHAP method was used to illustrate the prediction process of the LR model for neonatal postoperative AKI at the level of individual patients.

Conclusions: The ML model that uses the LR algorithm with eight commonly measured variables could serve as a tool to predict postoperative AKI in neonates.

Background: Febrile seizures (FSs) are the most common seizure disorder in children aged 6 months to 5 years, influencing approximately 2-5% of the global population, with a higher prevalence in men and those with a family history. Their complex pathogenesis involves fever-induced neuroinflammation, imbalances in neuronal excitation and inhibition, and genetic predispositions. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of gene expression and have been implicated in various neurological disorders. However, their specific roles in FSs remain underexplored. This systematic review aimed to summarize the epidemiology and pathophysiological mechanisms of FSs, elucidate the emerging roles of ncRNAs, and evaluate their potential as biomarkers and therapeutic targets.

Methods: A systematic literature search was conducted following the PRISMA guidelines. Electronic databases, including PubMed, Web of Science, and Embase, were searched using keyword combinations related to "Febrile Seizures" and "non-coding RNA". The screening process involved initial title/abstract review, full-text assessment, and final inclusion based on predefined criteria, with exclusions documented at each stage to ensure comprehensive coverage and minimize bias.

Results: The review highlighted that FS pathophysiology could be influenced by developmental characteristics of the nervous system (e.g., heightened neuronal excitability), immune responses (e.g., pro-inflammatory cytokines regulated by ncRNAs, such as miR-146a and miR-155), and genetic factors (e.g., ion channel genes post-transcriptionally controlled by ncRNAs, such as miR-134). Key ncRNAs, including miR-134 (associated with neuronal hyperexcitability), miR-146a (modulating neuroinflammation), and circHIPK2 (involving astrocyte activation), were identified as critical in seizure mechanisms based on animal models and mechanistic studies. NcRNAs demonstrate promise as biomarkers due to their stability in biological fluids, while challenges in sensitivity and specificity should be addressed. Therapeutically, targeting ncRNAs through strategies, such as antisense oligonucleotides for miR-134 or mimics for miR-146a shows promise in preclinical models. However, efficient delivery to the central nervous system remains a significant challenge.

Conclusions: NcRNAs serve as dynamic regulators in the pathogenesis of FSs, providing valuable insights for diagnosis and treatment. They hold remarkable potential as non-invasive biomarkers and therapeutic targets. However, future research should prioritize validating the findings in clinical cohorts, elucidating causal mechanisms, and addressing translational challenges, such as standardization and delivery systems, to advance personalized medicine for pediatric FSs.

Background: Neonates who are small for their gestational age (SGA) often experience poor immediate and long-term outcomes. However, more information is required to understand the prevalence of SGA in regional Australia and the associated risk factors. This study investigated the prevalence of SGA infants and examined its known risk factors from the literature from 2017 to 2019 among infants admitted to the postnatal ward (PNW) and special care nursery (SCN) in a regional centre providing care for infants born at or after 32 weeks gestation unless unavoidable deliveries of lesser gestation.

Methods: SGA infants were determined based on the birth weight below the 10th percentile using the Fenton Growth Chart. This retrospective observational study included eleven risk factors documented in the literature: maternal age (age <18 and >35 years), multiple pregnancies (>1), obstetric complications, chronic maternal complications, maternal infections, smoking, substance use, alcohol use, maternal body mass index (BMI) (<18.5 and >24 kg/m²), low socioeconomic status determined by postcode in Index of Relative Socio-economic Advantage and Disadvantage (IRSAD) map-2021, and prematurity (32 weeks gestation or later). Descriptive statistics and bivariate correlation were used for statistical analysis.

Results: Between 2017 and 2019, a total of 2,546 live births were recorded, and 100 infants were SGA born at or after 32 weeks in a regional centre. Of eleven known risk factors studied, the results showed socioeconomic status (99, 99.0%), smoking (63, 64.3%), and high maternal BMI (51, 52.6%) were the three most prevalent risk factors among SGA infants. There was a significant but minimal negative relationship between the birth weight of SGA infants and the number of associated risk factors [r(98)=-0.209, P=0.04]. All SGA infants had at least one associated risk factor, and more than half (N=54, 54.0%, Mode =5) presented with five and more risk factors (N=96, 96.0%, Mode =5).

Conclusions: The study found that 4% of infants were SGA at a regional centre, predominantly caring for infants born at or after 32 weeks gestation. SGA infants were more common in mothers with low maternal socioeconomic status, smoking and elevated BMI and the majority had two or more risk factors. Further research is required to compare the prevalence of SGA throughout regional Australia and to explore the associated risk factors further.

Background: Allergic rhinitis (AR) in children is a common condition with rising prevalence globally, causing a substantial negative impact on patient quality of life and an economic burden. While Western medicine provides symptom relief, recurrence rates and side effects remain concerns. Traditional Chinese medicine (TCM), through syndrome differentiation, offers an effective, affordable alternative. However, clinical diagnosis in TCM often relies on subjective judgment. Digital tongue image analysis, combined with clinical symptoms and medical history, may enhance the accuracy and objectivity of syndrome differentiation, offering a promising approach to more effective treatment for pediatric AR. This study aimed to assist clinicians in accurately distinguishing between cold and heat syndromes in pediatric patients with AR.

Methods: A total of 391 children with AR were included in this study. Patients were classified with cold syndrome (n=92) or heat syndrome (n=299). Patients were randomly divided into a training set (n=176) and a test set (n=215). A multimodal deep learning model was developed with three stages. First, a hybrid Dense Convolutional Network model with a Squeeze-and-Excitation (SE-DenseNet) module was used to extract features from tongue images. Second, the independent sample t-test was used to screen and select relevant features from patient demographic and clinical information and patient and family medical history. Third, a transformer model was used to integrate the features for cold and heat syndrome classification. Model performance was evaluated using area under the curve (AUC), accuracy, precision, recall, and F1 scores.

Results: The multimodal model outperformed other models when classifying children with AR as cold syndrome or heat syndrome. It had the best AUC, accuracy, precision, recall, and F1 score. In the training set, the AUC, accuracy, precision, recall, and F1 score were 0.931, 0.875, 0.949, 0.869, and 0.920, respectively. In the test set, the AUC, accuracy, precision, recall, and F1 score were 0.877, 0.856, 0.863, 0.829, and 0.910, respectively.

Conclusions: The multimodal model integrating clinical features and features from tongue images demonstrated high accuracy, with potential to assist pediatricians in syndrome differentiation and treatment decision-making for children with AR. The multimodal model may enable objective and quantifiable diagnostic results, improving efficiency and accuracy.

Background: Symmetrical peripheral gangrene (SPG) is a rare but devastating clinical syndrome marked by symmetrical distal ischemic damage in the absence of large vessel obstruction or vasculitis, usually resulting in high mortality and frequent limb amputations among survivors. The underlying causes are multifactorial, including both infectious and noninfectious factors. However, neither the implicated etiological factors nor the precise mechanisms of pathogenesis have been fully elucidated, making diagnosis and management particularly challenging.

Case description: This report describes a 14-year-old girl who initially exhibited fever, edematous extremities, widespread erythema and small blisters on the trunk and extremities, and subsequent blackening of the fingers and toes. Her condition rapidly progressed to sepsis, shock, disseminated intravascular coagulation (DIC), and early hemophagocytic syndrome, culminating in a diagnosis of SPG. Comprehensive etiological investigations revealed herpes simplex virus 2 (HSV-2) infection as the underlying cause. Through prompt multidisciplinary interventions-including mechanical ventilation, fluid resuscitation, vasopressors, antiviral therapy, anticoagulation, plasma exchange, immunosuppression, and meticulous wound care-the patient achieved a remarkable recovery, with only minor residual pigmentation on her extremities.

Conclusions: This case highlights HSV-2 as a rare but potential cause of SPG, broadening the spectrum of known pathogens. Early recognition, rapid diagnostic work-up, and timely multidisciplinary management are essential to improve outcomes and prevent limb loss.

Background: Perineurioma is a rare benign tumor of the peripheral nerve sheath, encompassing intraneural, traditional soft tissue, reticular, and sclerosing variants. Sclerosing perineurioma is a rare variation that predominantly manifests on the hands of young adults, presenting as a tiny, painless subcutaneous tumor. The incidence of pediatric perineurioma is very low, with only a few dozen cases reported in the literature. The primary cause for appointments at the outpatient clinic is a gradually enlarging asymptomatic tumor. The affected areas usually include the thumb (acral location). The lesions are typically solid, well-defined white masses with a fibrous texture, measuring 1.2-4.0 cm in maximum dimension.

Case description: We present a 2-year-6-month-old male with a sclerosing perineurioma of the left anterior chest wall and delineate the lesion's ultrasonographic and pathological characteristics.

Conclusions: This case report illustrates an almost unique pediatric instance of sclerosing perineurioma of the left anterior chest with additional, previously unreported imaging progression since birth. This case report is critical for general pediatrics and pediatric radiology. A description of this case aids in diagnosing extra-acral features of this tumor. Moreover, this case report may improve understanding of the imaging-pathology correlation of this tumor, benefiting both specialists and fellows.

Background: Growth hormone deficiency (GHD) requires accurate diagnosis, but the current gold standard, the growth hormone (GH) stimulation test, is highly invasive and resource-intensive, thus necessitating effective screening methods. Insulin-like growth factor 1 (IGF-1) is the most commonly utilized predictive marker for GHD. However, the consistency and accuracy of serum IGF-1 tests can be affected by patient characteristics and technical issues in blood analysis, which complicates its use as a reliable standalone marker. This study investigated the performance of the IGF-1/age ratio as a predictive marker for GHD and constructed a precise prediction model to mitigate these sources of variability in a single laboratory setting.

Methods: This cross-sectional study included 352 children aged 3 to 9 years who presented to Xi'an Children's Hospital for short stature and underwent the GH stimulation testing, which served as the gold standard for GHD diagnosis (peak GH cutoff of 10 µg/L). Key exclusion criteria were body mass index (BMI) ≥25 kg/m², history of GH therapy, secondary sexual characteristics, or chronic systemic diseases. Serum IGF-1 levels were measured using the IMMULITE^® 2000 Immunoassay System at our single center. The predictive performance of the IGF-1/age ratio was evaluated both alone and in combination with other markers. A precise prediction model was developed using a logistic regression algorithm, with feature selection guided by the Lasso method, and its performance was assessed using area under the curve (AUC) and calibration analysis. We designed a reference heatmap to facilitate its clinical use.

Results: A total of 117 participants (33.2%) exhibited GHD based on the GH stimulation test. The GHD group exhibited significantly lower levels of IGF-1 (82.19 vs. 155.69 ng/mL, P<0.001) and IGFBP-3 (3.63 vs. 4.09 µg/mL, P<0.001) and a significantly greater bone age delay (calculated as bone age - chronological age; -1.64 vs. -1.06 years, P<0.001) compared to the non-GHD group. Among all evaluated markers, the IGF-1/age ratio demonstrated the highest predictive performance, with an AUC of 0.921 [95% confidence interval (CI): 0.894-0.947]. Combined use with other markers further improved the performance. The prediction model using insulin-like growth factor binding protein 3 (IGFBP-3), IGF-1/IGFBP-3 ratio, IGF-1/age ratio, and BMI showed good discrimination (AUC of 0.936, 95% CI: 0.913-0.960) and good calibration (Hosmer-Lemeshow test P value of 0.74).

Conclusions: Based on data from this single-center study, our results suggest that the IGF-1/age ratio is a promising predictive marker that may be used to effectively stratify GHD risk and facilitate fast screening prior to definitive GH stimulation testing.

Background: Vitamin A and vitamin D₃ are essential micronutrients for child growth and development. However, previous studies have shown inconsistent results with respect to their individual and combined effects on anthropometric outcomes. We aimed to conduct a systematic review and meta-analysis to assess the impact of vitamin A, vitamin D₃, and their combination on child growth.

Methods: Randomized controlled trials (RCTs) that evaluated the effects of vitamin A, vitamin D₃, or their combination on growth in children aged 0-14 years (primary population: children aged 0-5 years; secondary exploratory analyses: 0-14 years) were included. Data were pooled using fixed- or random-effects models, and heterogeneity was assessed with the I-squared (I²) statistic.

Results: A total of 12 RCTs involving 6,340 children were included. Vitamin D₃ supplementation alone had no significant effect on height-for-age Z-score (HAZ) (Z=0.43, P=0.67) or weight-for-height Z-score WHZ (Z=0.52, P=0.61), but was associated with a modest yet statistically significant improvement in weight-for-age Z-score (WAZ) (Z=2.72, P=0.007), though the clinical relevance of this finding remains uncertain. Vitamin A supplementation alone had no significant impact on HAZ, WAZ, or WHZ. Among children aged 0-5 years, combined supplementation of vitamins A and D₃ showed a small but significant improvement in WAZ (Z=2.16, P=0.03), but no consistent effects on HAZ or WHZ. Substantial heterogeneity was observed in the combined group (I²>70%), attributable to variability in supplement formulations, dosages, and study populations.

Conclusions: Neither vitamin A nor vitamin D₃ alone significantly improved child growth. Combined supplementation may provide modest benefits in weight gain but is insufficient to address linear growth or acute malnutrition. Future strategies should adopt multi-nutrient approaches and consider contextual factors such as infection control, dietary diversity, and socioeconomic conditions.

Background: High-risk neuroblastoma (NB) still carries a <50% long-term survival despite risk-adapted therapy. Conventional risk metrics (age, stage, MYCN status) fail to capture transcriptional programs that drive tumor aggressiveness and immune escape. We hypothesized that systematic transcription factor (TF) activity profiling would reveal clinically actionable NB subtypes. This study aimed to profile TF activities in NB to develop and validate a TF-based prognostic score and to examine its association with the tumor immune microenvironment.

Methods: TF activities for 498 primary NB tumors (GSE49710) were inferred with decoupleR-univariate linear model (ULM) using the OmniPath regulon. TFs that were significantly associated with overall survival (OS; Cox; P<1×10-4; n=146) were subjected to consensus clustering and Boruta-guided principal component analysis (PCA) to create a continuous TF_score. Immune infiltration and immunotherapy surrogates, Immunophenoscore (IPS) and the Tumor Immune Dysfunction and Exclusion (TIDE) framework, were compared across TF_score strata. A nomogram integrating TF_score, stage, and MYCN amplification was developed and validated with an external cohort (E-MTAB-8248; n=223) and single-cell RNA sequencing (RNA-seq) data.

Results: Two robust NB subtypes were identified, with cluster 2 associated with worse prognosis, MYCNamplification, older age, distinct pathway activation, and higher stemness indices. The TF_score reliably quantified these clusters, showing superior predictive capability for survival compared to traditional markers (MYCN amplification and tumor stage). TF_score-high patients exhibited reduced immune infiltration and lower predicted responsiveness to immunotherapy. A validated prognostic nomogram effectively stratified risk, highlighting MYC and E2F family activation and FOXO3 and IRF1 suppression in high-risk patients. Single-cell analyses confirmed these bulk RNA-seq findings.

Conclusions: TF activity profiling provides robust stratification for NB, integrating clinical prognostication and immune characterization. This study offers novel insights into TF-driven NB biology, with implications for targeted therapy and immunotherapeutic strategies.