Translational pediatrics最新文献

Background: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and highly aggressive malignancy predominantly affecting children and adolescents. Managing UESL is particularly intricate due to its aggressive nature and the limited array of treatment options available. This study is dedicated to elucidating the efficacy of a multimodal therapeutic strategy in the successful management of UESL.

Case description: Four pediatric patients (two males, two females; aged 6-11 years) diagnosed with UESL were treated at the Children's Hospital of Nanjing Medical University between November 2019 and June 2023. Surgical resection with lymph node dissection achieved complete primary tumor eradication. Adjuvant chemotherapy tailored to each patient's needs was followed by localized radiation therapy. After 9-42 months of follow-up, one patient who did not undergo immediate radiotherapy experienced a relapse. Following a second operation coupled with radiotherapy, the patient achieved complete remission, and mirroring the status of the other three patients who are now presently in remission. The overall cohort exhibited commendable tolerance to the treatment regimen, with manageable chemotherapy-related toxicities.

Conclusions: This case series suggests that implementing a standardized protocol of resection, followed by adjuvant chemotherapy and radiation, can lead to favorable outcomes in pediatric patients diagnosed with UESL. Nevertheless, the need for comprehensive large-scale studies is imperative to substantiate the effectiveness of this approach.

Background: Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease.

Methods: In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE).

Conclusions: Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.

Background and objective: Cerebral palsy (CP) is the most common motor disability in children. The initial lesion to the developing brain may result in a myriad of neuromuscular comorbidities, including mobility deficiencies. The neuromuscular contributions to disability and rehabilitative frameworks specific to children with CP have been investigated separately. However, few reviews have examined the relationship between neuromuscular pathophysiology and rehabilitative frameworks among children with CP. Therefore, the purpose of this review was to investigate the impact of dynamic stretching orthoses and therapeutic exercise on range of motion (ROM), aerobic capacity, and mobility in relation to the neuromuscular contributions to disability in children with CP.

Methods: Reviews of PubMed, Google Scholar, and Web of Science were conducted to identify literature focusing on the neuromuscular pathophysiology contributing to disability in children with CP and rehabilitative frameworks associated with this population. The search used a combination of keywords and subject headings to include 'cerebral palsy', 'musculoskeletal', 'neuromuscular', 'spasticity', 'rehabilitation', 'exercise', 'aerobic', and 'orthosis'. Selected manuscripts featured original cross-sectional and longitudinal research and meta-analyses.

Key content and findings: A total of 303 manuscripts were initially identified through search terms, with 182 articles excluded based on title and abstract evaluation, leaving 121 manuscripts for full-text analysis. Seven studies meeting the narrative review criteria were included. Evidence supporting the efficacy of dynamic stretching orthoses for improving lower extremity ROM is inconclusive. Aerobic and progressive resistive training may be beneficial for improving aerobic capacity and muscle strength in children with CP, which may result in enhanced mobility.

Conclusions: Depending on the individual's clinical presentation, ROM and therapeutic exercise may be implemented to optimize function. Incorporating progressive resistive and aerobic exercises into a rehabilitation plan may improve mobility and aerobic capacity. As such, clinicians should consider resistance and aerobic exercise prescription as part of a long-term treatment plan for children with CP.

Background: The etiology of short stature is heterogeneous. The disturbance of endochondral ossification and cartilage matrix synthesis caused by genetic mutations often causes short height combined with skeletal deformities in children. Some patients with minor skeletal abnormalities, such as short fingers and mild limb shortening, may be overlooked by clinicians and misdiagnosed as idiopathic short stature (ISS) or growth hormone deficiency (GHD).

Case description: We conducted a detailed investigation of laboratory and imaging examinations on a family with short stature and non-classical brachydactyly type A1 (BDA1) and summarized the clinical features. They received whole exome sequencing (WES) to reveal the possible genetic variation. A heterozygous mutation in the Indian hedgehog gene (IHH) (c.387_388insC, p.Thr130Hisfs*18) was found in the two siblings and their mother. The siblings both started recombinant human growth hormone (rhGH) therapy (rhGH: 33 µg/kg/day) and followed up for 4 years. After treatment, the siblings' height improved significantly, and they acquired a significant increase in the height standard deviation score (SDS) (the boy: +2.54, the girl: +1.86) during the 4-year therapy. No noticeable adverse effect was observed during rhGH treatment.

Conclusions: We found a novel heterozygous pathogenic mutation in the IHH gene in a family and detailed the phenotype with short stature and non-classical BDA1. The therapy of rhGH showed promising effects. To avoid misdiagnosis, clinicians should not overlook minor skeletal anomalies in patients with short stature, especially those with a family history.

Background: Caroli syndrome or Caroli disease is characterized by focal dilation of the intrahepatic bile ducts, with or without congenital liver fibrosis. Mutations in the WDR19 gene can result in nephropathy, an autosomal recessive cystic kidney disease. However, this genetic mutation is clinically associated with Caroli syndrome or disease. We hypothesize that WDR19 gene mutations may contribute to extrarenal phenotypes such as Caroli disease or syndrome.

Case description: The outpatient department received a 1-year-old male patient with persistent dilated bile ducts for over four months. Subsequent ultrasound examination revealed liver cirrhosis, splenomegaly, and cystic dilatation of the intrahepatic bile duct. He was subsequently admitted for comprehensive diagnosis and treatment. Accordingly, we performed computed tomography (CT)-hepatic portal venography, magnetic resonance-cholangiography, and the plain liver scan, the results revealed liver cirrhosis, splenomegaly, cystic dilatation of the intrahepatic bile duct, as well as atypical hyperplasia nodules in the right posterior lobe of the liver and lymphatic hyperplasia and enlargement in the porta hepatis and the space between the liver and stomach. As the possibility of early small liver cancer could not be excluded due to the presence of nodules, surgical resection was performed followed by pathological examination and whole genome exome testing. The pathological findings revealed hepatocyte swelling, hydropic degeneration, and sporadic necrosis. Fibrous tissue hyperplasia was observed in the portal vein area, along with local pseudolobule formation. Also, numerous small bile duct hyperplasia was observed with lymphocyte infiltration, which is consistent with cirrhosis. Moreover, the hepatocytes of the small focal area showed atypical hyperplasia. Considering the above findings, Caroli syndrome was diagnosed. The genetic results showed two heterozygous mutations in the WDR19 gene, c.2290delC (p.Q764Nfs*29) and c.2401G>C (p.G801R). Therefore, the child's intrahepatic bile duct dilatation and cirrhosis were considered as the manifestations of Caroli syndrome caused by mutations in the WDR19 gene.

Conclusions: Mutations in the WDR19 gene can manifest as Caroli disease or Caroli syndrome. For the definite diagnosis of liver diseases of unknown etiology, whole exome sequencing may be more conducive.

[This corrects the article DOI: 10.21037/tp-23-387.].

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Background: Isolated fetal ventriculomegaly can have a range of consequences, ranging from mild neurodevelopmental delay to perinatal death; the extent of these consequences often depend on the severity of ventriculomegaly. This systematic review and meta-analysis aims to investigate the impact of the degree of ventricular dilatation on the risk of neurodevelopmental delay and adverse perinatal outcomes in fetuses diagnosed with isolated fetal ventriculomegaly from gestational week 15 onwards.

Methods: PubMed, Embase, Scopus and the Cochrane Library were searched electronically to identify studies investigating the prognosis of mild and/or severe isolated fetal ventriculomegaly. Articles were included if they reported neurodevelopmental or perinatal outcomes in fetuses prenatally diagnosed with isolated fetal ventriculomegaly from week 15 of gestation and onwards. Studies were excluded if they reported on non-isolated ventriculomegaly (IVM), failed to specify the degree of ventriculomegaly, were non-English papers, animal studies or published outside of the 21-year period of interest. Study quality was assessed by two independent reviewers using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Ventriculomegaly was defined as either mild or severe when ventricular diameter measured as 10-15 or >15 mm, respectively. Meta-analyses were conducted for adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality.

Results: Following the removal of duplicates, the search yielded 2,452 citations, of which 23 studies were included and 8 were eligible for meta-analysis. There were 767 and 347 cases of mild and severe isolated fetal ventriculomegaly, respectively. Adverse outcomes were consistently reported at a higher rate in severe cases than mild. The relative risks of adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality were 4.24 [95% confidence interval (CI): 2.46-7.30], 4.46 (95% CI: 1.64-12.11) and 6.02 (95% CI: 1.73-21.00), respectively, upon comparison of mild versus severe cases of isolated fetal ventriculomegaly.

Conclusions: The likelihood of adverse neurodevelopmental and perinatal outcomes, including intrauterine and infant mortality, is increased in severe isolated fetal ventriculomegaly compared to mild isolated fetal ventriculomegaly.

Background: Adolescent idiopathic scoliosis (AIS) is a prevalent spinal disorder that can potentially influence bone mineral density (BMD), thereby increasing the susceptibility to osteoporosis and fractures. Early identification of reduced bone mass in AIS patients is crucial for clinicians to develop effective preventive strategies against fractures. This study aims to elucidate the correlation between BMD, as measured by quantitative computed tomography (QCT), and various clinical parameters in AIS, including the Cobb angle, vertebral rotation, and the Risser sign. By revealing the potential influences of these factors on BMD, our findings aim to assist clinicians in making informed and timely decisions regarding AIS management, particularly in situations where QCT is unavailable.

Methods: A cross-sectional study was conducted on 129 adolescents with AIS who were enrolled at The Third People's Hospital of Chengdu, Sichuan, China, between 2021 and 2023. QCT was employed to assess BMD and vertebral rotation. The Cobb angle and Risser sign were determined through radiographic evaluation, while anthropometric and biochemical data were also collected. Statistical analyses, including Pearson and Spearman rank correlation and regression models, were used to investigate the associations between BMD and clinical measures.

Results: A significant negative correlation was found between BMD and Cobb angle (coefficient =-0.663; P<0.001), as well as between BMD and vertebral rotation angle (coefficient =-0.442; P<0.001) in patients with AIS. BMD was positively correlated with increased height (coefficient =0.355; P<0.001) and BMI (coefficient =0.199; P=0.02). A significant association was detected between BMD and the Risser sign (P=0.002). No significant sex-based differences in BMD were observed (P=0.052). No significant correlations were observed between BMD and levels of potassium (K), calcium (Ca), inorganic phosphate (P), and iron (Fe) (P>0.05 all). The binary logistic regression analysis identified Cobb angle as a risk factor of lower BMD presence in AIS patients (coefficient =0.072; OR=1.075; P<0.001). Furthermore, the receiver operating characteristic (ROC) analysis of the combined model for predicting low BMD in AIS patients yielded an area under the curve (AUC) value of 0.900, with an optimal threshold determined as 0.398. The sensitivity and specificity were calculated as 0.816 and 0.900, respectively, indicating a robust predictive capacity.

Conclusions: This study highlights the significant inverse correlation observed between BMD measured by QCT and both Cobb angle and vertebral rotation angle in patients with AIS. Furthermore, a notable variation in BMD was found across different Risser sign categories, with BMD values generally increasing as Risser sign levels increased. Additionally, our findings indicate that Cobb angle serves as a risk factor for low B