Clinical and Experimental Pediatrics

Review Article

Oncology

Breaking the barrier: a guidelines-based review of antiangiogenesis drug resistance in pediatric cancer therapy

Nader Shakibazad, Mahdi Shahriari, Mani Ramzi

Clin Exp Pediatr. 2025;68(12):952-962. Published online November 24, 2025

Antiangiogenic therapy resistance in pediatric cancers involves alternative angiogenic pathways, microenvironmental support, hypoxia-driven signaling, metabolic reprogramming, and structural adaptations such as vascular co-option. Metabolic adaptation highlights tumor plasticity. Effective treatments combine immunotherapy with biomarkers. To address vascular endothelial growth factor limitations, emerging targets include hypoxia-inducible factor-2α, endoglin, CXCR4, angiopoietin/Tie2, and bispecific antibodies. In resource-constrained settings, the guidelines recommend low-dose chemotherapy plus oral multiantiangiogenic agents to ensure improved accessibility and treatment outcomes.

DOI: https://doi.org/10.3345/cep.2025.01809

Nutrition

Exploring nutritional screening tools for hospitalized children: a narrative review

Pankaj Soni, Amit Agrawal, Gaurav Jadon

Clin Exp Pediatr. 2025;68(12):963-970. Published online October 22, 2025

Malnutrition is frequently identified in hospitalized children, and the use of nutritional screening tools is crucial for assessing their nutritional status during their hospital admission and stay. Common tools include the Pediatric Yorkhill Malnutrition Score, Screening Tool for Assessment of Malnutrition in Pediatrics, and Screening Tool for Risk of Nutritional Status and Growth. However, these tools have varying sensitivities and specificities, and none is recommended for all hospitalized children.

DOI: https://doi.org/10.3345/cep.2025.00633

Editorial

Infection

Beyond COVID-19: meeting the challenge of evolving pediatric invasive group A streptococcal disease

Han Wool Kim

Clin Exp Pediatr. 2025;68(12):971-973. Published online November 26, 2025

Pediatric for invasive group A Streptococcus has resurged globally with increasing severity and toxin-mediated presentations. Beta-lactams remain the first-line treatment, but linezolid has emerged as a safe alternative in cases refractory to β-lactams. Early intravenous immunoglobulin use may improve outcomes in severe streptococcal toxic shock syndrome cases, while C-reactive protein and procalcitonin aid early risk stratification. Integrating global surveillance and individualized therapy is crucial in the postpandemic era.

DOI: https://doi.org/10.3345/cep.2025.02600

Original Article

Oncology

HLA‒B*58:01 and skin reactions in pediatric hematology and oncology patients treated with allopurinol

Parisa Maneechai, Cholada Ratanatharathron, Jassada Buaboonam, Kleebsabai Sanpakit

Clin Exp Pediatr. 2025;68(12):974-980. Published online October 2, 2025

Crossref 1

Question: Does human leukocyte antigen (HLA)–B*58:01 increase the risk of cutaneous reactions in pediatric patients with hematological and oncological diseases receiving allopurinol?
Finding: : Of 108 patients, 17.6% carried HLA–B*58:01 but none developed skin reactions. The only rash occurred in an HLA-B*58:01–negative patient.
Meaning: Short-duration allopurinol may mitigate severe cutaneous adverse reaction risk regardless of genotype. Routine HLA-B*58:01 screening may be unnecessary in pediatric patients with hematological and oncological diseases briefly receiving allopurinol.

DOI: https://doi.org/10.3345/cep.2025.01032

Hematology

Assessment of natural killer cell subpopulations in pediatric patients with transfusion-dependent β-thalassemia major

Fathia Ibrahim Elbassal, Mohamed Abdel Rehim Soliman, Nourhan Hossam Eldin Mohamed, Mai El-Sayad Abd El-Hamid, Hanan Hassan El-Sheity

Clin Exp Pediatr. 2025;68(12):981-990. Published online September 12, 2025

Question: How does iron overload affect immunity in pediatric patients with transfusion-dependent β-thalassemia major?
Finding: Iron overload in these patients is associated with disrupted natural killer (NK) cell subpopulations, reflecting impaired innate immunity.
Meaning: This highlights the need to monitor immune profile alongside iron status during thalassemia management.

DOI: https://doi.org/10.3345/cep.2025.01046

Neonatology (Perinatology)

Less invasive surfactant administration versus intubation-surfactant-extubation: a single-center retrospective study

C.S. Jithin, A. Nalina, A. Shashidhar, P.N. Suman Rao

Clin Exp Pediatr. 2025;68(12):991-997. Published online October 2, 2025

Question: Does less invasive surfactant administration (LISA) (vs. intubation-surfactant-extubation) improve clinical outcomes in preterm infants with respiratory distress syndrome?
Finding: LISA significantly reduced intubation and invasive mechanical ventilation needs within the first 72 hours and shortened the overall invasive respiratory support duration without increasing other morbidities.
Meaning: LISA is a less invasive and safer surfactant delivery alternative. Larger multicenter trials are needed to confirm its long-term safety and efficacy, especially in low- and middle-income countries.

DOI: https://doi.org/10.3345/cep.2025.00332

Infection

Association between vitamin D polymorphisms and binding protein and COVID-19 risk and severity in children

Victoria Giatraki, Helen Dimitriou, Georgia Martimianaki, Christos Tsatsanis, Emmanouil Galanakis, Chrysoula Perdikogianni

Clin Exp Pediatr. 2025;68(12):998-1006. Published online October 22, 2025

Question: Addressing crucial genetic variants within the vitamin D pathway and coronavirus disease 2019 (COVID-19) susceptibility, the vitamin D receptor, vitamin D binding protein, and CYP27B1-1260 polmorphisms might be associated with COVID-19 occurrence and severity in children.
Finding: The FokI FF genotype might be an independent risk factor for COVID-19 severity in childhood.
Meaning: This research may further elucidate genetic susceptibility to multisystem viral infections and establish genetic markers for severe clinical outcomes.

DOI: https://doi.org/10.3345/cep.2025.00577

Clinical outcomes and healthcare utilization of hospitalized children with influenza versus COVID-19

David Chun-Ern Ng, Chuin-Hen Liew, Kah Kee Tan, Joanne Pereira, Muhammad Ihsan Roslan, Xiang Lin Cheng, Hui Yi Lim, Farah Nuruliayana A. Nazri, Asuwani Maran, Wan Fei Wong, Yasothai Chandran, Syaniza Shaharudin, Pon Ling Lau, Naveen Nair Gangadaran, Marlindawati Mohd Ali

Clin Exp Pediatr. 2025;68(12):1007-1014. Published online October 2, 2025

Question: How do clinical presentations, healthcare resource utilization, and outcomes differ between children hospitalized with influenza versus coronavirus disease 2019 (COVID-19)?
Finding: Patients with influenza were older, were more symptomatic, and required greater healthcare resources, including intravenous fluids, empirical antibiotics, respiratory support, and pediatric intensive care unit admission.
Meaning: Influenza involves greater severity and a higher healthcare burden than COVID-19, highlighting the need for preventive strategies such as vaccination and hospital resource planning during seasonal outbreaks.

DOI: https://doi.org/10.3345/cep.2025.00759

Critical Care Medicine

Cytokine profile of Post–cardiopulmonary bypass in children

Kantara Saelim, Kanokpan Ruangnapa, Jirayut Jarutach, Pongsanae Duangpakdee, Smonrapat Surasombatpattana, Pharsai prasertsan

Clin Exp Pediatr. 2025;68(12):1015-1022. Published online September 19, 2025

Question: Can cytokine levels predict low cardiac output syndrome (LCOS) in children post–cardiopulmonary bypass?
Finding: Elevated interleukin (IL)-6, IL-8, and tumor necrosis factor-α levels were associated with LCOS, with an increase in IL-8 of >56 pg/mL from baseline to immediately postoperative being the strongest predictor.
Meaning: Monitoring immediately postoperative IL-8 levels may help identify pediatric patients at risk of LCOS, enabling timely interventions to improve outcomes.

DOI: https://doi.org/10.3345/cep.2025.00836

Pulmonology

Ciclesonide shows a lung-protective effect in neonatal hyperoxia-exposed rats

Victoria Mielgo, Miguel A. Gomez-Solaetxe, Lara Olazar, Begoña Loureiro, Carmen Rey-Santano

Clin Exp Pediatr. 2025;68(12):1023-1030. Published online October 2, 2025

Question: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease of prematurity. Numerous nonpharmacological/pharmacological interventions have been investigated without clear consensus. Can ciclesonide, a new synthetic glucocorticoid, effectively treat BPD?
Finding: Ciclesonide mitigated hyperoxia-induced lung injury and right ventricular hypertrophy in newborn rats.
Meaning: These findings suggest that postnatal ciclesonide may be an alternative to existing corticosteroids for the treatment of BPD.

DOI: https://doi.org/10.3345/cep.2025.01137

General Pediatrics

Lipoprotein(a) prevalence trends in Portuguese children and adolescents: a real-world perspective

Isabel Morais Ribeiro, Susete Vieira, Miguel Saraiva, Mónica Tavares, José Carlos Oliveira, Isabel Mangas Palma, Helena Ferreira Mansilha

Clin Exp Pediatr. 2025;68(12):1031-1040. Published online November 24, 2025

Early lipid screening, including lipoprotein(a) (Lp(a)), in children/adolescents is key to identifying and managing dyslipidemia and reducing the risk of early-onset cardiovascular disease. This study shows that prevalence of elevated Lp(a) in high-risk Portuguese children is alarming, with over 30% at intermediate/high risk and nearly 1% at very high-risk (>430 nmol/L). Since Lp(a) is mostly genetically determined, one-time early screening in atrisk children is crucial for timely monitoring and prevention.

DOI: https://doi.org/10.3345/cep.2025.00339

Clinical Note

Gastroenterology

Successful rescue after catastrophic bleeding of carotid artery pseudoaneurysm following button battery ingestion in a toddler

Manjit Kaur, Ujjal Poddar, Basant Kumar, Abdul Muzil Munshi, Rajanikant R. Yadav, Moinak Sen Sarma, Anshu Srivastava

Clin Exp Pediatr. 2025;68(12):1041-1044. Published online October 22, 2025

Button battery (BB) ingestion is an increasing hazard. Catastrophic gastrointestinal bleeding due to pseudoaneurysm rupture following BB impaction is often fatal. Here we report the case of an unwitnessed BB ingestion in an 18-month-old boy who presented with repeated massive UGIB due to a left CCA pseudoaneurysm that was successfully managed multidisciplinarily. BB ingestion should be considered in toddlers presenting with hematemesis.

DOI: https://doi.org/10.3345/cep.2025.01347

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