Translational pediatrics最新文献

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.

Background: There was limited research comparing retinal nerve fibre layer (RNFL) involvement among different mitochondrial DNA (mtDNA) mutations associated with varying visual prognoses. This study aimed to observe and compare the thickness changes of RNFL among Leber's hereditary optic neuropathy (LHON) patients with G11778A, T14484C and G3460A mtDNA mutations.

Methods: A retrospective cross-sectional analysis was conducted on LHON patients with G11778A (189 eyes of 121 patients), T14484C (20 eyes of 10 patients), or G3460A (28 eyes of 15 patients) mutations, enrolled between July 2017 and December 2020. We also recruited age-matched healthy individuals as the healthy control group. Patients were grouped based on their mutation type and disease duration (<6, 6-12, and >12 months). RNFL thickness measurements were obtained for all quadrants and compared among the three mutation groups.

Results: During the subacute phase, the temporal quadrant RNFL thickness in LHON patients with G11778A, T14484C, or G3460A mutations was significantly reduced compared to healthy controls. In the dynamic phase, the RNFL thickness in all quadrants of G11778A or G3460A LHON patients was significantly thinned, except for the nasal quadrant in LHON patients with G3460A mtDNA mutation (P=0.29). As the disease progressed, RNFL thickness in all quadrants and average RNFL thickness were significantly thinner in all three mutation groups relative to controls, except for the nasal quadrant in T14484C mutation patients (P=0.10). Furthermore, during both the subacute and dynamic phases, RNFL thickness in all quadrants was thinner in G11778A and G3460A mutation patients compared to T14484C mutation patients.

Conclusions: The papillomacular bundle was the initial and preferential site of involvement in LHON patients across all mutation types. The pattern of RNFL involvement was similar among the three mutations: temporal quadrant thinning occurred first, followed by the inferior and superior quadrants, and finally the nasal quadrant. Patients with G11778A and G3460A mutations exhibited earlier and more pronounced RNFL atrophy compared to those with T14484C mutations.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening emergency in neonatal intensive care. Traditional treatments such as cylinder-based nitric oxide (NO) delivery systems rely on large, fixed equipment, creating limitations during neonatal transport or treatment in primary hospitals, which may delay critical intervention. Moreover, neonates exhibit high physiological vulnerability, imposing stricter requirements on the safety and portability of therapeutic devices. Novlead Biotech in China has developed a novel portable inhaled nitric oxide (iNO) generator (PG-iNO), which shows promise in overcoming these obstacles. This study aims to assess the safety of PG-iNO for the treatment of PPHN using a descriptive study.

Methods: The data of seven newborns diagnosed with PPHN and having received PG-iNO from December 1, 2023 to January 31, 2024 were retrieved from medical records. Demographic and clinical features, vital signs, arterial blood gas, ventilation indicators, measurement of preductal and postductal oxygen saturation, mortality, and comorbidities were evaluated before and after the administration of PG-iNO therapy.

Results: All enrolled patients survived and reported few side effects during the administration of PG-iNO. A significant improvement in oxygenation index (OI), fraction of inspired oxygen (FiO₂), mean airway pressure (MAPaw), and arterial partial pressure of oxygen (PaO₂) was observed before and 48 hours after initiating PG-iNO therapy.

Conclusions: The PG-iNO demonstrates safety in the treatment of neonatal PPHN. However, large-scale, prospective trials are needed to further validate its long-term safety and efficacy, particularly in preterm infants.

Background: At present, there are many treatment options for childhood IgA vasculitis nephritis (IgAVN), but the optimal treatment method remains unclear, and high-quality evidence to guide treatment decisions is still limited. This study identifies the best drugs for childhood IgAVN via Bayesian network meta-analysis (NMA).

Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, as well as Sinomed were comprehensively retrieved for pertinent randomized controlled trials (RCTs) examining various methods of treating childhood IgAVN with medication. NMA was enabled by R 4.2.2. The risk of bias was rated via the Cochrane Risk of Bias 2.0 (RoB 2.0). The effect size was estimated using the mean difference (MD), risk ratio (RR), or odds ratio (OR) and 95% confidence interval (CI). The effects of intervention methods were ranked using the surface under the cumulative ranking curve (SUCRA). The certainty of the evidence was examined via the Confidence in Network Meta-Analysis (CINeMA) approach. Possible publication bias was detected through funnel plots generated via Stata 18.0.

Results: This study encompassed 73 RCTs. In comparison to standard of care (Soc), steroid therapy demonstrated the most favorable overall efficacy in IgAVN children (RR =1.17, 95% CI: 1.02-1.34). Leukotriene (LT) receptor antagonists were the most effective in reducing urinary protein (UP) levels (OR =13.28, 95% CI: 9.12-17.45)..Other therapies excelled in specific parameters.

Conclusions: Steroids offer the most effective therapeutic approach for childhood IgAVN, though its safety profile needs further study. More research is required for clinical decisions.

Background: Children and adolescents with cerebral palsy (CP) are known to have higher dental caries prevalence due to interacting clinical, behavioral, and socioeconomic factors. Although caregiver burden and suboptimal oral health practices have been implicated, their relative contributions remain unclear. This study aimed to determine caries prevalence in children and adolescents with CP, assess caregiver burden, and identify key predictors of increased caries risk.

Methods: This cross-sectional analytical study was conducted across two hospitals in Kuala Lumpur. Clinical data, including the Gross Motor Function Classification System (GMFCS) levels and CP subtypes, were extracted from patient medical records. Dental caries prevalence was assessed using the Decayed, Missing, and Filled Teeth (DMFT)/decayed filled teeth (dft) index, while caregiver burden was measured using the Zarit Burden Interview. Binary logistic regression was used to identify predictors of dental caries prevalence.

Results: A total of 110 children and adolescents with CP and their caregivers participated in the study. The prevalence of caries in primary teeth (70.3%) was consistent with the national average (71.3%). However, for permanent teeth (77.3%), it was over twice the national caries prevalence (33.3%) in 12-year-old children. The Care Index was notably low for both primary and permanent teeth at 6.1% and 20.0%, respectively. On average, caregiver burden was mild to moderate. Binary logistic regression revealed that children with GMFCS levels IV and V were 25.1 times [95% confidence interval (CI): 4.54-138.90] more likely to exhibit dental caries than those at GMFCS levels I-III.

Conclusions: This study demonstrates that children and adolescents with CP experience high caries prevalence and unmet dental treatment needs. On average, the caregivers experience mild to moderate burden and severe motor impairment (GMFCS IV-V) is the sole key predictor of caries risk in children and adolescents with CP. Hence, the GMFCS classification serves as a reliable tool for stratifying caries risk in children and adolescents with CP. Targeted dental caries prevention, early intervention, regular monitoring, and multidisciplinary care involving pediatricians, rehabilitation teams and the pediatric dental team are imperative to improve oral health outcomes.