Clinical and Experimental Pediatrics最新文献

Background: Lipoprotein(a) (Lp(a)) is a plasma lipoprotein with atherogenic, prothrombotic, and proinflammatory properties. Elevated Lp(a) levels are linked to the development of early atherosclerosis in childhood and contribute to a higher risk of cardiovascular disease (CVD) in adulthood.

Purpose: This study aimed to assess the clinical significance of Lp(a) levels in Portuguese pediatric patients who underwent serum Lp(a) testing as part of a lipid disorder screening prompted by obesity, hypercholesterolemia, and/or a family history of premature CVD. We also evaluated the correlation between Lp(a) levels and CVD risk factors.

Methods: This cross-sectional retrospective study included 792 pediatric patients. Data on demographics, clinical history, body mass index, and laboratory values, including Lp(a), were collected. Lp(a) levels were categorized into 3 groups: <75 nmol/L, 75-125 nmol/L, and >125 nmol/L. A multivariate analysis was used to identify factors associated with Lp(a) ≥ 75 nmol/L.

Results: The most prevalent comorbidities in this sample were obesity and associated low-grade inflammation, each affecting at least one-third of participants. The median Lp(a) level was 31.80 nmol/L, with 9.1% and 21.6% of children having intermediate (75-125 nmol/L) and high (>125 nmol/L) Lp(a) levels, respectively. Higher total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels were correlated with elevated Lp(a) levels. The multivariate analysis identified an elevated LDL-C level as a predictor of a higher Lp(a) level.

Conclusion: This study highlights the alarming prevalence of elevated Lp(a) levels in Portuguese pediatric patients who underwent serum Lp(a) testing due to lipid disorder screening, with >30% at intermediate/high CVD risk. As Lp(a) levels are mostly genetically determined and tend to persist into adulthood, these findings emphasize the importance of including Lp(a) screening in the cardiovascular risk assessment of children with CVD risk factors to enable timely prevention strategies for adultonset CVD.

The growth and metastatic potential of most solid and hematological tumors are angiogenesis-dependent. Antiangiogenic therapies have demonstrated clinical advantages in the treatment of numerous tumor types. Nevertheless, resistance to antiangiogenic therapy has emerged over time. This study aimed to review physiological blood vessel growth, angiogenesis, tumor vasculature, the role of vascular endothelial growth factor and its receptor in tumor angiogenesis, antiangiogenesis, resistance to antiangiogenic therapy, and mechanisms of resistance to antiangiogenic treatment while also providing guidance for the development of antiangiogenic therapies. We reviewed Google Scholar and PubMed for studies examining antiangiogenesis therapy, resistance to antiangiogenic agents, and strategies for overcoming them, thereby creating a guidelines-based approach. This review discusses a novel adaptive resistance mechanism involving metabolic adaptability of tumor cells. We found that personalized medicine may enhance the angiogenic mechanisms utilized by tumors. Thus, antiangiogenic therapy should be personalized by incorporating insights into tumor-specific vascularization and metabolism along with biomarker-guided treatment strategies. In addition to developing new pharmaceuticals, we must prioritize the identification of reliable markers for pathway activation and response. Addressing these challenges enables the optimization of antiangiogenic treatments within a precision oncology framework, thereby enhancing the prediction of therapeutic benefits and minimizing the risk of resistance in pediatric malignancies. In addition to conventional or salvage chemotherapy, antiangiogenic agents may serve as adjunctive chemotherapeutic agents, particularly for solid tumors. We also provide a guidelines-based approach to pediatric cancer therapy using antiangiogenic agents in countries with limited resources.

Background: Bronchopulmonary dysplasia (BPD), a chronic lung disease primarily observed in premature infants, is attributed to a lung injury-repair imbalance. Studies of postnatal corticosteroids have failed to identify clear candidates to help alleviate high BPD rates without risks or adverse effects.

Purpose: This study aimed to assess whether the systemic postnatal administration of an alternative glucocorticoid, ciclesonide, could attenuate alterations in lung structure and right ventricular hypertrophy in a hyperoxic rat BPD-like model.

Methods: In a hyperoxia-induced model of BPD-like lung injury, pups were maintained in oxygen-enriched atmosphere-hyperoxia or normoxia (room air) for 14 days after natural birth, and subcutaneous ciclesonide (0.5 mg/kg) was administered postnatally for 5 consecutive days. On postnatal day 14, lung function (peak inspiratory pressure and compliance), lung structure (radial alveolar count, mean linear intercept, and pulmonary vessel density), and right ventricular hypertrophy were assessed.

Results: On day 14, the effects of hyperoxia exposure were more evident in untreated rats (impaired lung compliance and structure and right ventricular hypertrophy) than in normoxia-exposed animals. Ciclesonide administration was associated with smaller body weight changes and significantly improved lung compliance, alveolarization, lung vascular growth, and right ventricular hypertrophy.

Conclusion: Postnatal ciclesonide administration preserved lung function and structure and prevented right ventricular hypertrophy in a hyperoxic BPD-like model. These findings suggest that postnatal ciclesonide may be an alternative to existing corticosteroids for the treatment of BPD. However, long-term studies are required to validate these findings.

Background: In recent years, minimally invasive methods have been increasingly utilized for surfactant administration in spontaneously breathing preterm infants with respiratory distress syndrome (RDS) managed with nasal continuous positive airway pressure owing to their feasibility and association with improved respiratory outcomes. However, data are limited from developing countries on the use and effectiveness of these techniques.

Purpose: The primary objective of this study was to evaluate the effect of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) techniques on the need for intubation and invasive mechanical ventilation (MV) within 72 hours of surfactant administration in preterm neonates with RDS. The secondary objectives were the effects of these methods on the need for a second surfactant dose, mortality rate, and other preterm morbidities.

Methods: This retrospective observational study was conducted in Southern India over 5 years. Clinical outcomes were analyzed in neonates with RDS at 24-34 weeks' gestation who received surfactants via the LISA or InSurE method.

Results: A total of 98 neonates were divided into the LISA group (n=54) and the InSurE group (n=44). The need for intubation and MV within 72 hours was significantly lower in the LISA versus InSurE group (18% vs. 64%, P=0.04; relative risk, 0.28; 95% confidence interval, 0.16-0.53). The duration of invasive ventilation was significantly shorter in the LISA group (P<0.001). We observed no significant intergroup differences in the need for a second surfactant dose (17% vs. 7%, P=0.14), bronchopulmonary dysplasia (3.7% vs. 8.8%, P=0.49), or mortality (14.5% vs. 13%, P=0.47).

Conclusion: LISA appears to be a less invasive and more effective alternative to InSurE, demonstrating the ability to reduce the need for intubation and invasive ventilation within the first 72 hours as well as the duration of invasive support in preterm infants with RDS.

Background: Third-generation cephalosporins remain the empirical mainstay for pediatric urinary tract infections (UTIs) in Korea, yet the resistance rate now approaches 30%, thereby threatening treatment effectiveness.

Purpose: To determine whether completing a cephalosporin regimen, despite in vitro resistance, increases early UTI recurrence rates.

Methods: We retrospectively reviewed the cases of children aged <24 months with their first Gram-negative UTI admitted in 2020-2024. Three exposure groups were defined: susceptible isolates treated with a third-generation cephalosporin; resistant isolates that received ≥5 days of antibiotics to which the isolated organism was susceptible (concordant); and resistant isolates that received <5 days of appropriate antibiotic therapy (discordant). The primary outcome was UTI recurrence within 2 months. Kaplan- Meier curves were generated, while multivariate Cox models adjusted for age, fever, acute cortical defects, and kidney anomalies were used to estimate hazard ratios (HRs).

Results: Among 989 children (mean age, 4.4 months), 424 (42.9%) had cefotaxime-resistant isolates; of them, 76 (17.9%) received concordant therapy and 348 (82.1%) received discordant therapy. The overall 2-month recurrence rate was 15.4% (95% confidence interval [CI], 13.0-17.7). Compared to the susceptible group, the concordant group did not show a significantly different relapse rate (adjusted HR [aHR], 1.09; 95% CI, 0.67-1.78), whereas the discordant group demonstrated an increased recurrence risk (aHR, 1.42; 95% CI, 1.08-1.86). An analysis of culture-confirmed recurrence yielded similar findings (discordant therapy aHR, 1.82; 95% CI, 1.29-2.56). No significant differences were observed when the analysis was restricted to febrile recurrence.

Conclusion: Completing a third-generation cephalosporin course when isolates are not susceptible to thirdgeneration cephalosporins can increase early UTI recurrence rates in Korean children. Reviewing susceptibility on day 5 and switching to an active oral agent may reduce recurrence and limit unnecessary broad-spectrum antibiotic exposure.

Sacral dimples are the most common cutaneous anomalies in newborns. While usually benign anatomical variants, some dimples are indicative of occult spinal dysraphism, such as a tethered cord, dermal sinus tract, or lipomyelomeningocele, that, if undiagnosed, may cause irreversible neurological, orthopedic, and urological deficits. Distinguishing benign from high-risk dimples is essential for timely intervention. This review summarizes the embryological origins, diagnostic criteria, imaging approaches, and management strategies for sacral dimples to help clinicians identify cases requiring further evaluation. A comprehensive literature review examines the embryology of caudal spinal development, classification of spinal dysraphism, and studies of the diagnostic accuracy of ultrasonography and magnetic resonance imaging (MRI) in infants with sacral dimples. Guidelines and high-quality studies of the surgical outcomes of tethered cords and related anomalies were also analyzed. The literature search and study selection followed the Preferred Reporting Items for Systematic Reviews and Meta- Analyses flow. Simple sacral dimples-solitary midline depressions less than 5 mm in diameter, located within 2.5 cm of the anus, and lacking associated cutaneous stigmata- are not associated with spinal dysraphism and do not require imaging. In contrast, atypical dimples (large, deep, off-midline, or associated with skin markers such as hair tufts or hemangiomas) are significantly associated with occult anomalies and warrant imaging, beginning with spinal ultrasonography in neonates and MRI in older infants or equivocal cases. Conditions such as tethered cord, dermal sinus tract, lipomyelomeningocele, and split cord malformations are best visualized using MRI. Early surgical detethering improves neurological, orthopedic, and bladder outcomes, whereas delayed intervention risks permanent deficits. Applying standardized criteria and targeted imaging avoids unnecessary investigations while ensuring a timely diagnosis of occult spinal dysraphism. Early recognition and appropriate surgical management, when indicated, are critical for preventing neurological deterioration and improving the prognosis of affected infants.

Background: Clinical, biochemical, histological, and immunological indicators are frequently used to diagnose autoimmune hepatitis (AIH), a chronic inflammatory liver disease affecting children. Wilson disease, which resembles AIH, is mainly evaluated using serum ceruloplasmin and copper levels. However, changes in these biomarkers have also been observed in AIH, raising the question of whether they could be useful for evaluating children with AIH.

Purpose: When selecting a treatment plan and estimating the long-term prognosis of patients with AIH, assessing the liver fibrosis stage is crucial. It is also crucial to identify noninvasive indicators of liver fibrosis, for which ceruloplasmin has been suggested as a biomarker in several liver diseases. Therefore, this study aimed to investigate the potential significance of serum ceruloplasmin and copper levels for identifying liver fibrosis in children with AIH.

Methods: One hundred children with AIH treated at Menoufia University's National Liver Institute Pediatric Hepatology, Gastroenterology, and Nutrition Department were enrolled. The duration of the study was 5 years (February 2020 to February 2025). The patients' histopathological, radiographic, laboratory, and clinical data were collected. We used the revised score to diagnose AIH. A Beckman Coulter AU480 chemistry analyzer was used to measure serum copper, while an enzyme-linked immunosorbent assay was used to measure serum ceruloplasmin.

Results: Serum ceruloplasmin levels were considerably lower in patients with advanced fibrosis (F3-4) than in those without advanced fibrosis (F0-2) (P<0.001). However, in patients with extensive fibrosis, the serum copper levels were considerably elevated (P<0.001). Compared to serum copper level, which had an area under a curve of 0.939 (95% confidence interval [CI], 0.887-0.991; P<0.001) and a cutoff of >24.7 mg/dL (90.8% sensitivity, 66.9% specificity), ceruloplasmin level had an area under a curve of 0.945 (95% CI, 0.889-1.00; P<0.001), suggesting that it could be a useful tool for the detection of advanced liver fibrosis in children.

Conclusion: To estimate the long-term prognosis of patients with AIH, it is crucial to assess liver fibrosis stage. It is crucial to identify noninvasive indicators of liver fibrosis, for which ceruloplasmin has been suggested as a biomarker. Therefore, serum copper and ceruloplasmin levels may provide important information for the identification of advanced liver fibrosis in children with AIH.

Background: The postacute sequelae of coronavirus disease 2019 (PASC), also known as pediatric long coronavirus disease (COVID), can significantly affect the quality of life (QoL) of affected children. Currently, there are no standardized screening tools to identify high-risk children. The Kinder Lebensqualität fragebogen (KINDL) is a psychometric method for measuring QoL in children.

Purpose: This study used the KINDL questionnaire and Children's Somatic Symptom Inventory-24 (CSSI-24) to evaluate symptom burden and establish a screening threshold for pediatric PASC.

Methods: We performed a cross-sectional study of children diagnosed with PASC defined as the presence of at least one persistent symptom lasting more than 4 weeks after a confirmed COVID-19 infection. Symptoms were assessed using a structured checklist developed by our team. The correlation between the KINDL and CSSI-24 scores was analyzed, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal KINDL cutoff for identifying high-risk cases. QoL scores were also compared with those of historical cohorts to evaluate the impact of the PASC.

Results: We included 84 participants: 46 children (mean age, 8.74±1.77 years; 41.3% girls) and 38 adolescents (mean age, 14.50±1.56 years; 44.7% girls). KINDL and CSSI-24 scores showed a significant negative correlation (r=-0.44, P<0.001), suggesting that increased somatic symptoms were associated with a reduced QoL. The ROC analysis identified a KINDL cutoff score of 74.75 (area under the curve, 0.82) for detecting high-risk children. Compared to historical cohorts, children with PASC had QoL scores comparable to child-reported norms from 2010 but lower than parent-reported norms from the same year.

Conclusion: KINDL and CSSI-24 are practical tools for screening for pediatric PASC in outpatient settings. A KINDL cutoff of 74.75 may help clinicians identify children with PASC who require early intervention. Further studies in larger and more diverse populations are required to validate these findings.