Frontiers in Pediatrics最新文献

Background: The genetic variations in aplastic anemia (AA) patients are closely related to clonal hematopoiesis, but there is limited research on this topic in children with AA. The aim of this study is to investigate the molecular classification and outcomes of children with AA combined with myeloid neoplasm-associated gene variants.

Methods: The clinical features, types of gene variants, mechanisms of action of the mutated genes, and correlations between gene variants and the outcomes of AA patients with myeloid neoplasm-associated gene variants were retrospectively analyzed.

Results: Forty-six AA patients with myeloid neoplasm-associated gene variants were included, and a total of 20 gene variants were identified. The most frequent variant affected TET2 (9 patients, 19.6%), followed by ASXL1 (5 patients, 10.9%) and MPL (5 patients, 10.9%). Other variants, in descending order, affected TERT (4 patients); SH2B3, FLT3, ETV6, and JAK2 (3 patients each); BCOR, BCORL1, TP53, KIT, and SF3B1 (2 patients each); and CALR, GATA2, RUNX1, CBL, IDH1, IDH2, and WT1 (1 patient each). Six patients had 2 gene variants. The original mechanisms of action of the mutated genes mainly involved epigenetics and signal transduction pathways; both groups of genes were affected in 39.1% (18/46) of the patients. The difference in the efficacy of immunosuppressive therapy (IST) among the different gene groups was not significant. Disease severity (P = 0.046) and hematological response at 3 months (P = 0.002), 6 months (P = 0.001), 9 months (P = 0.001), and 1 year (P = 0.001) were important factors affecting survival time, but genotype was not. None of the patients experienced clonal evolution by the end of the follow-up cut-off time.

Conclusion: In patients with AA combined with myeloid tumor neoplasm-associated gene variants, TET2, ASXL1 and MPL variants were the most frequently observed and primarily involved epigenetics and signal transduction pathways. There was no significant difference in the efficacy of IST among patients with different gene variants. Survival time was associated with disease severity, and the development of a hematological response-particularly when achieved at 3 months-was an independent key factor, whereas genotype was not.

Background: Mixed-phenotype acute leukemia (MPAL) is a rare and heterogeneous subtype of acute leukemia, associated with unfavorable outcomes. MPAL is defined by the presence of more than 20% blasts and bi- or trilineage assignment based on strong immunophenotypic markers, with specific subcategories characterized by BCR::ABL1, KMT2A, ZNF384, or BCL11B rearrangements. This review aims to summarize current knowledge and challenges in the diagnosis and management of MPAL.

Methods: Data were synthesized primarily from meta-analyses and original studies, with a particular emphasis on the roles of immunophenotyping, cytogenetics, and novel targeted therapies from 1985 to the present.

Results: MPAL accounts for 1%-5% of acute leukemias, with B/myeloid (59%) and T/myeloid (35%) subtypes being the most prevalent. Cytogenetic abnormalities are identified in up to 90% of cases, predominantly complex karyotypes. Molecular investigations have identified frequent mutations in genes such as RUNX1, DNMT3A, IDH1/2, NOTCH1, and FLT3, particularly enriched in T/myeloid MPAL. Adverse prognostic factors include KMT2Ar, elevated leukocyte counts, extramedullary disease, and bilineage disease biology. Generally, the prognosis for adults is poorer than for the pediatric population. No standardized treatment strategy has been established. Retrospective analyses indicate superior complete remission rates and overall survival with ALL-based regimens, and allogeneic hematopoietic stem cell transplantation remains crucial for improving survival. Recently, hybrid regimens such as FLAG-IDA and CLAG-M have demonstrated promising efficacy with acceptable toxicity. Targeted therapies are emerging options, although lineage switch under selective therapeutic pressure remains a concern.

Conclusions: MPAL remains a significant challenge in diagnosis and treatment. Advances in molecular characterization have enhanced classification techniques and have the potential to inform personalized treatment strategies. Considering the rarity and heterogeneity of MPAL, extensive prospective multicenter trials are imperative to develop evidence-based therapeutic protocols.

Background: The impact of red blood cell (RBC) storage duration during cardiopulmonary bypass (CPB) priming in pediatric cardiac surgery remains unclear.

Objective: To evaluate whether RBC storage time affects perioperative outcomes in children undergoing cardiac surgery.

Methods: We performed a systematic review and meta-analysis of studies comparing fresh vs. longer-stored RBCs for CPB priming in pediatric patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science (through May 2025). Primary outcomes were mortality, infection/sepsis, respiratory complications, and multiple organ dysfunction syndrome (MODS); secondary outcomes included mechanical ventilation duration, ICU stay, and intraoperative lactate levels.

Results: Ten studies (including one randomized controlled trial) were included. No significant differences were found between groups in any primary or secondary outcomes, except for a slightly shorter ICU stay in the fresh RBC group (mean difference = -1.08 days), with high heterogeneity.

Conclusions: RBCs stored within standard durations appear safe for CPB priming in pediatric cardiac surgery. These findings support current transfusion practices and underscore the need for further high-quality randomized trials.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1015198, PROSPERO CRD420251015198.

Background: Idiopathic scoliosis (IS) is a three-dimensional spinal deformity that often progresses during adolescence. While bracing and exercise therapies are standard conservative treatments, limited research has examined the feasibility of fully online, home-based combined exercise programs and the clinical trends observed during participation -especially in adolescents undergoing brace treatment. This single-arm prospective cohort study (without a control group) aimed to evaluate the feasibility of a six-month, fully online, home-based Schroth-Pilates program combined with brace treatment in adolescents with IS, and to observe potential age-related trends in clinical measures and adherence.

Methods: A single-center prospective cohort design was used involving 114 adolescents with IS (Cobb angle 10°-45°) receiving standard brace treatment. Participants engaged in supervised online Schroth-Pilates sessions three times per week for six months. Primary measures included Cobb angle and ATR, recorded at baseline and post-program. Feasibility was assessed via program completion and adherence rates. Mixed-design ANOVAs were used to explore trends over time and between age groups (10-13 vs. 14-17 years).

Results: The overall program completion rate was 97.4%, with no significant adherence differences between age groups. Significant improvements were observed in Cobb angle [F(1,112) = 16.42, p < .001, η ² = .255] and ATR [F(1,112) = 11.87, p = .001, η ² = .198], both exceeding the minimum clinically important difference for adolescents with IS. Higher adherence was positively correlated with greater reductions in Cobb angle and ATR, suggesting that consistent participation enhanced treatment outcomes. Younger participants demonstrated greater mean improvements, possibly reflecting higher flexibility and growth potential.

Conclusion: A fully online, home-based Schroth-Pilates program is feasible and clinically effective for adolescents with IS, achieving high adherence and meaningful improvements in spinal curvature and trunk rotation-particularly among younger participants. These results support the clinical viability of virtual scoliosis rehabilitation and highlight the need for future controlled and longitudinal studies to confirm long-term outcomes.

The Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is highly malignant neoplasms composed of undifferentiated small round cells with the ability to differentiate into various tissue types. We reported the case of an 11-year-old boy who presented with unsteady gait, progressive back pain, bilateral lower limb weakness (more pronounced in the left leg), and urinary retention. Magnetic resonance imaging (MRI) demonstrated a uniformly intense extradural lesion at the T3-5 vertebral level on the left posterolateral side of the spinal canal. The lesion measured 1.35 cm × 4.8 cm on pre-contrast MRI and 4.8 cm × 1.8 cm × 1.2 cm on post-contrast imaging, causing anterior and rightward displacement of the spinal cord with associated intramedullary signal changes and moderate post-contrast enhancement. Preoperative imaging suggested possible diagnoses of lymphoma or lipovascular tumor. However, postoperative histopathological examination confirmed the diagnosis of a small round cell malignant tumor consistent with an ES/PNET. The rapid progression to intramedullary metastasis and poor outcome emphasize the need for early diagnosis and more effective treatment strategies. Spinal ES/PNET is extremely rare, and this case highlights the clinical presentation, diagnostic challenges, and histopathological features of this aggressive tumor, which remain poorly reported in the literature.

Background: This study evaluated the diagnostic efficacy of combining pepsinogen (PG I/II), gastrin-17 (G-17), and ¹³C-urea breath test (13C-UBT) for chronic gastritis in children using logistic regression and receiver operating characteristic (ROC) analysis.

Methods: Between June 2018 and August 2023, 65 children with chronic gastritis and 50 healthy controls participated. Inclusion criteria for both groups: Age 6-12 years, chronic gastritis confirmed by endoscopy and histopathology for the gastritis group, and absence of GI symptoms for the control group. Exclusion criteria: Severe cardiopulmonary dysfunction, gastroduodenal surgery, recent use of PPIs/antibiotics, and H. pylori eradication therapy. Serum levels of PG I, PG II, and G-17 were determined by ELISA, and 13C-UBT was used to detect Helicobacter pylori (Hp) infection.

Results: Combined detection showed significantly higher positive rates than individual PG I/II or G-17 tests (P < 0.05), but similar to 13C-UBT alone. Chronic gastritis patients had elevated PG I, and G-17 levels compared to controls (P < 0.05). Multivariate analysis identified PG I (OR = 1.048, P = 0.014), G-17 (OR = 1.943, P < 0.001), and 13C-UBT positivity (OR = 17.417, P < 0.001) as significant predictors. ROC analysis revealed AUCs of 0.692 (PG I), 0.594 (PG II), 0.782 (G-17), 0.808 (13C-UBT), and 0.844 (combined), with sensitivity ≥90.8% and specificity >78%.

Conclusion: The combined detection of PG I/II, G-17, and 13C-UBT shows strong diagnostic potential for Helicobacter pylori-associated chronic gastritis in children, offering enhanced diagnostic accuracy and a non-invasive tool for early screening and intervention.

Background: Artificial intelligence (AI), particularly AI-based large language models (LLM) like ChatGPT, is increasingly shaping how information is accessed, offering patients a new source for understanding complex medical conditions. Given the physical, emotional, and logistical challenges that parents are faced when their baby is diagnosed with developmental dysplasia of the hip (DDH), the demand for clear and accessible educational resources is high. This study aimed to evaluate the quality and reliability of ChatGPT's responses to frequently asked questions about DDH.

Methods: This study assessed the quality of responses generated by the AI chatbot ChatGPT 4o to eight frequently asked questions about DDH, derived from real consultations in a pediatric orthopedic clinic Responses were generated during one interaction per question using a ChatGPT account not previously exposed to medical information. Responses were evaluated by two individual readers using a standardized rating system, comparing them to current literature, patient education resources, and consensus guidelines. Each response was categorized by its level of informational accuracy and completeness, and descriptive statistics were calculated to quantify performance.

Results: ChatGPT 4o was able to generate structured responses to all eight parental questions. The responses were rated in 12.5% excellent, 25.0% satisfactory with minimal clarification, 50.0% satisfactory with moderate clarification, and 12.5% unsatisfactory due to missing or inaccurate information.

Conclusion: ChatGPT provided satisfactory answers to questions about DDH and may serve as a useful supplementary information resource for parents. However, due to limitations in presenting detailed diagnostic and treatment pathways, it should be viewed as an adjunct to, not a replacement for, specialist medical consultation.

Background: Although central nervous system fungal infection (CNSF) is uncommon, it is a life-threatening condition that requires prompt diagnosis and management. Here, we report a full-term female neonate with suspected CNSF diagnosed by magnetic resonance imaging (MRI) despite repeatedly negative cerebrospinal fluid (CSF) and blood cultures, in whom the causative pathogen could not be identified.

Case presentation: A full-term female neonate presented on the first day of life with irritability, hypoactivity, cyanosis, poor feeding, and two episodes of generalized tonic-clonic seizures with up-rolling of the eyes and lip smacking. Workup for neonatal sepsis showed negative CSF and blood cultures. MRI findings suggested CNSF, and treatment was initiated with low-dose conventional amphotericin B deoxycholate (0.5 mg/kg/day) for 4 weeks, leading to complete clinical and radiological resolution.

Conclusion: Negative CSF and blood cultures do not exclude neonatal CNSF. In resource-limited settings, MRI findings together with clinical response to antifungal therapy may support a diagnosis of probable CNSF, even when the pathogen is not identified and standard high-dose regimens are not available.

Background: Recombinant factor IX-albumin fusion protein (rIX-FP) enables extended-interval prophylaxis for hemophilia B. While higher trough levels with reduced dosing frequency have been shown vs. standard FIX products, age-related differences in pharmacokinetics (PK) may constrain extended intervals in children. We aimed to refine a population PK (popPK) model of rIX-FP to inform clinically practical dosing across pediatric, adolescent, and adult patients.

Methods: Pooled FIX activity data from 113 previously treated patients (1-63 years) in five clinical studies were analyzed with a two-compartment popPK model. Covariates included body weight, age, weight-adjusted dose, and ethnicity (Japanese vs. non-Japanese). Model performance was evaluated by standard diagnostics and prediction-corrected visual predictive checks. Simulations estimated single-dose duration above 5% FIX activity and steady-state troughs for common prophylactic regimens stratified by age (<6, 6-<12, 12-<18, ≥12, ≥18 years).

Results: Body weight significantly influenced clearance (CL) and volumes; weight-normalized CL was faster in children, especially <6 years. No meaningful ethnic effect was detected; PK parameters and simulated profiles were comparable between Japanese and non-Japanese patients. Simulations showed that in patients ≥12 years, median steady-state troughs were maintained around ∼5% with 25-50 IU/kg weekly, 50 IU/kg every 10 days, 75 IU/kg every 14 days, and 100 IU/kg every 21 days-supporting a 3-week option in well-controlled patients. In contrast, children <6 years generally required weekly dosing (≥40-50 IU/kg) to achieve ∼5% troughs; extending intervals substantially reduced the proportion meeting target levels.

Conclusion: rIX-FP supports individualized prophylaxis with extended intervals up to 3 weeks in patients ≥12 years while younger children typically require more frequent dosing due to higher weight-normalized clearance. These PK-based insights can guide shared decision-making to balance protection, treatment burden, and patient preference across pediatric and adolescent age groups.