Clinical and Experimental Pediatrics最新文献

Background: Influenza and coronavirus disease 2019 (COVID-19) are major causes of pediatric respiratory illness with overlapping clinical features but potentially differing impacts on healthcare utilization and outcomes.

Purpose: To compare the clinical presentations, healthcare resource utilization, and outcomes of children hospitalized with influenza and COVID-19 and address the gaps in pediatric data from Southeast Asia.

Methods: This retrospective observational study included children aged ≤12 years hospitalized with laboratory-confirmed influenza or COVID-19 at a tertiary hospital in Malaysia between May 1, 2022, and May 1, 2023. Patients with viral or bacterial coinfections were excluded. Influenza A and B cases were collectively analyzed. The patients' demographic data, clinical presentation, resource utilization, and outcomes were also evaluated. Propensity score matching (PSM) was performed to balance the cohorts for age, sex, ethnicity, and comorbidities. Outcomes were compared using standardized mean differences (SMDs).

Results: A total of 299 patients were included (influenza, n=177; COVID-19, n=122). Patients with influenza were older (median, 3.6 years vs. 1.8 years; P<0.001) and more likely to have fever, cough, and rhinorrhea. COVID-19 patients presented earlier in the illness (median, 2 days vs. 4 days; P<0.001). After PSM, 102 patients were included in each group. Patients with influenza required greater healthcare resource use, including intravenous fluids (60.8% vs. 43.1%; SMD=0.36), empirical antibiotics (40.2% vs. 12.7%; SMD=0.66), respiratory support (40.2% vs. 26.5%, SMD=0.29), pediatric intensive care unit admission (10.8% vs. 2.9%; SMD=0.32), and longer duration of oxygen therapy (SMD=0.93).

Conclusion: Children hospitalized for influenza demonstrated higher clinical severity and greater healthcare resource utilization than those hospitalized for COVID-19. These findings highlight the burden of influenza and inform hospital resource planning during periods of viral circulation.

Background: Allopurinol is widely used to prevent hyperuricemia in patients with tumor lysis syndrome. However, its use can trigger severe cutaneous adverse reactions (SCARs) with a mortality rate of approximately 11.39%. The human leukocyte antigen (HLA)-B*58:01 genotype is a major risk factor for SCARs. Although most studies to date have examined HLA-B*58:01 in Thai adults, data on pediatric patients are limited.

Purpose: Here we aimed to evaluate the association between HLA-B*58:01 and skin reactions in children with hematological or oncological diagnoses receiving allopurinol and determine its prevalence in this population.

Methods: Pediatric patients (age≤18 years) with hematological or oncological diseases who received allopurinol were enrolled in this cross-sectional study of previously exposed and newly prescribed cases. HLA-B*58:01 genotyping was performed to assess its association with skin reactions.

Results: A total of 108 patients (mean age, 9.3 years) were included. Most patients (n=93, 86.1%) received allopurinol as prophylaxis for tumor lysis syndrome. Of them, 75 (69.4%) received allopurinol concomitantly with chemotherapy for malignancies, whereas the remaining patients received allopurinol during conditioning for hematopoietic stem cell transplantation. The prevalence of HLA-B*58:01 positivity was 17.6% (n=19 of 108 patients). The median exposure duration was 5 days (range, 1-19 days). No HLA-B*58:01-positive patients experienced a skin reaction. However, one patient who tested negative for HLA-B*58:01 developed a maculopapular rash on day 2 of the allopurinol therapy and required intravenous antihistamines.

Conclusion: Short-duration allopurinol exposure likely mitigates the risk of SCARs regardless of HLA-B*58:01 status. Routine HLA-B*58:01 testing may not be warranted in pediatric patients receiving brief allopurinol courses. However, larger studies are required to confirm these findings.

Malnutrition is common among hospitalized children, especially those who are critically ill. Routine measures, such as anthropometric measurements, body composition, and nutritional assessment, comprise the basics of monitoring. This review discusses the adequacy of nutritional screening tools (NSTs) such as the SGNA (Subjective Global Nutritional Assessment), PYMS (Pediatric Yorkhill Malnutrition Score), STAMP (Screening Tool for the Assessment of Malnutrition in Paediatrics), and STRONGkids (Screening Tool for Risk of Nutritional Status and Growth). This review included recently published reports supporting the validation and implementation of NSTs in pediatric populations. A child's nutritional status during hospitalization is of great importance for their recovery, while the implementation of screening tools enhances their clinical outcomes. Current tools have varying sensitivities and specificities, and no single tool can be recommended for all groups of hospitalized children. A combination of tools or adaptation of existing tools with validation in different contexts might be ideal. Further studies are required to develop more robust and comprehensive screening tools.

Background: The effects of genetic background on the biological effects of vitamin D on coronavirus disease 2019 (COVID-19) in children remain unclear.

Purpose: This study aimed to explore the association between vitamin D-related genetic background and 25-hydroxyvitamin D status and COVID-19 occurrence and severity in children. Here we explored key genetic variants within the vitamin D pathway in pediatric COVID-19 patients in relation to circulating vitamin D binding protein (VDBP).

Methods: Sixty children aged 0-14 years with severe acute respiratory syndrome coronavirus 2 infection and 60 matched controls were genotyped for the vitamin D receptor (VDR) gene (FokI, BsmI, TaqI, ApaI), Gc gene of VDBP (rs7041, rs4588), and CYP27B1 promoter (rs10877012) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism assay.

Results: The FokI FF genotype was more frequently identified among COVID-19 patients than controls, among whom the TaqI TT genotype was prevalent (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.08-4.73; P=0.02; and OR, 0.29; 95% CI, 0.13-0.63; P=0.001, respectively). The Gc1F haplotype was significantly more represented in controls versus COVID-19 patients (OR, 0.39; 95% CI, 0.19-0.81; P=0.01). A 2.04-fold increased risk of COVID-19 was observed in the presence of the VDR FokI F allele (OR, 2.04; 95% CI, 1.14-3.64; P=0.01). A multivariate analysis revealed a significant association between the FokI FF genotype and disease severity (OR, 0.20; 95% CI, 0.04-0.83; P=0.02). Serum VDBP levels were similar between groups.

Conclusion: The FF genotype of the VDR FokI polymorphism may be associated with COVID-19 and have a significant clinical impact on disease severity in children.

Background: Open cardiac surgery involving cardiopulmonary bypass (CPB) triggers a systemic inflammatory response that significantly affects clinical outcomes. However, the dynamics and specific roles of cytokine release after CPB in the pediatric population remain unclear.

Purpose: To evaluate the dynamics of cytokine levels and their association with low cardiac output syndrome (LCOS)-related outcomes.

Methods: A prospective observational cohort study was conducted of 32 children who underwent elective open cardiac surgery with CPB at Songklanagarind Hospital, Thailand. Levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were analyzed preoperatively and immediately (T0), 6, 12, and 24 hours after intensive care unit admission. LCOS-related outcomes were defined with at least two of the following criteria being met within 24 hours postoperative: clinical and laboratory parameters, vasopressor-inotropic score ≥20, ejection fraction <50% on echocardiography; and requirement for a serious postoperative intervention. Statistical analyses utilized linear mixed models and multivariate logistic regression to identify the independent predictors of LCOS.

Results: The mean patient age was 34.8±34.4 months; 56.2 % were male. Roughly one-third (37.5%) had a history of previous cardiac surgery, while one-quarter (28.3%) had a Risk Adjustment for Congenital Heart Surgery score ≥3. LCOS-related outcomes occurred in 37.5% of patients. IL-6, IL-8, and TNF-α levels differed significantly between patients with and without LCOS outcomes. An increase in IL-8 of >56 pg/mL from baseline to T0 showed the strongest association with LCOS (odds ratio, 37.34; 95% confidence interval, 4.53-836.53).

Conclusion: An elevated postoperative IL-8 level is a robust predictor of LCOS-related outcomes in pediatric patients undergoing cardiac surgery. These findings emphasize the importance of monitoring cytokine dynamics to guide interventions and improve patient outcomes.

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.