Search Results (950)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Background: Point-of-care ultrasound (POCUS) is gaining recognition as a valuable diagnostic tool in various fields of medicine, including pediatrics. Its application at the point of care enables real-time clinical decision-making, which is particularly advantageous in pediatric settings. Although global interest in POCUS is growing, many European countries—including Poland—still lack formal training programs for POCUS at both the undergraduate and postgraduate levels. Nevertheless, the number of pediatricians incorporating POCUS into their daily clinical practice in Poland is increasing. However, the extent of its use and perceived value among pediatricians remains largely unknown. This study aimed to evaluate the current level of POCUS utilization in pediatric care in Poland, focusing on pediatricians’ self-assessed competencies, perceptions of its clinical utility, and key barriers to its implementation in daily practice. Methods: This cross-sectional study was conducted between July and August 2024 using an anonymous online survey distributed to pediatricians throughout Poland via national professional networks, with a response rate of 7.3%. Categorical variables were analyzed using the chi-square test of independence to assess the associations between key variables. Quantitative data were analyzed using descriptive statistics, and qualitative data from open-ended responses were subjected to a thematic analysis. Results: A total of 210 pediatricians responded. Among them, 149 (71%) reported access to ultrasound equipment at their workplace, and 89 (42.4%) reported having participated in some form of POCUS training. Only 46 respondents (21.9%) reported frequently using POCUS in their clinical routine. The self-assessed POCUS competence was rated as low or very low by 136 respondents (64.8%). While POCUS was generally perceived as a helpful tool in facilitating and accelerating clinical decisions, the main barriers to implementation were a lack of formal training and limited institutional support. Conclusions: Although POCUS is perceived as clinically valuable by the surveyed pediatricians in Poland, its routine use remains limited due to training and systemic barriers. Future efforts should prioritize the development of a validated, competency-based training framework and the implementation of a larger, representative national study to guide the structured integration of POCUS into pediatric care. Full article

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children and comprises four molecular subtypes—WNT, SHH, Group 3, and Group 4—each with distinct genetic, epigenetic, and metabolic features. Increasing evidence highlights the critical role of metabolic reprogramming and epigenetic alterations in driving tumor progression, therapy resistance, and clinical outcomes. This review aims to explore the interplay between metabolic and epigenetic mechanisms in medulloblastoma, with a focus on their functional roles and therapeutic implications. Methods: A comprehensive literature review was conducted using PubMed and relevant databases, focusing on recent studies examining metabolic pathways and epigenetic regulation in medulloblastoma subtypes. Particular attention was given to experimental findings from in vitro and in vivo models, as well as emerging preclinical therapeutic strategies targeting these pathways. Results: Medulloblastoma exhibits metabolic adaptations such as increased glycolysis, lipid biosynthesis, and altered amino acid metabolism. These changes support rapid cell proliferation and interact with the tumor microenvironment. Concurrently, epigenetic mechanisms—including DNA methylation, histone modification, chromatin remodeling, and non-coding RNA regulation—contribute to tumor aggressiveness and treatment resistance. Notably, metabolic intermediates often serve as cofactors for epigenetic enzymes, creating feedback loops that reinforce oncogenic states. Preclinical studies suggest that targeting metabolic vulnerabilities or epigenetic regulators—and particularly their combination—can suppress tumor growth and overcome resistance mechanisms. Conclusions: The metabolic–epigenetic crosstalk in medulloblastoma represents a promising area for therapeutic innovation. Understanding subtype-specific dependencies and integrating biomarkers for patient stratification could facilitate the development of precision medicine approaches that improve outcomes and reduce long-term treatment-related toxicity in pediatric patients. Full article

Background: Despite its central role in pediatric pre-surgical evaluation of drug-resistant focal epilepsy, conventional analog ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT (aPET) systems often yield modest epileptogenic zone (EZ) detection rates (~50–60%). Silicon photomultiplier–based digital PET/CT (dPET) promises enhanced image quality, but its performance in pediatric epilepsy remains untested. Methods: We retrospectively analyzed 22 children (mean age 11.5 ± 2.6 years) who underwent interictal brain ¹⁸F-FDG PET/CT: 11 on an analog system (Discovery ST, 2018–2019) and 11 on a digital system (Biograph Vision 450, 2020–2021). Three blinded nuclear medicine physicians independently scored EZ localization and image quality (4-point scale); post-surgical histology and ≥1-year clinical follow-up served as reference. Results: The EZ was correctly identified in 8/11 analog scans (72.7%) versus 10/11 digital scans (90.9%). Average image quality was significantly higher with dPET (3.0 ± 0.9 vs. 2.1 ± 0.9; p < 0.05), and inter-reader agreement improved from good (ICC = 0.63) to excellent (ICC = 0.91). Conclusions: Our preliminary findings suggest that dPET enhances image clarity and reader consistency, potentially improving localization accuracy in pediatric epilepsy presurgical workups. Full article

Diagnosing hypermobility disorders and Ehlers-Danlos syndrome (EDS) in children is challenging due to overlapping features with generalized joint hypermobility (GJH) and the lack of biomarkers. Background/Objectives: This study aims to describe the clinical and genetic features of pediatric EDS patients and identify key comorbidities and correlations. Methods: This is a single-center observational study of patients under 18 diagnosed with suspicion of EDS (2018–2024) at a tertiary pediatric hospital. Diagnoses were made using 2017 criteria. Results: Forty-one patients (46% female; mean age 11.1 ± 2.8 years) were included. Based on 2017 criteria, 61% had hypermobile EDS (hEDS)/hypermobility spectrum disorder (HSD), 22% classical EDS, 7.3% vascular, and 9.7% other subtypes. Musculoskeletal (90.2%), cutaneous (68.3%), and psychiatric (56.1%) symptoms were most frequent. Significant associations included older age with psychiatric symptoms (p = 0.029), Beighton score with dislocations (p = 0.026), and less atrophic scarring in hEDS (p < 0.008). Genetic testing (73% performed) confirmed pathogenic variants (11 novel) in EDS with a known molecular cause. Conclusions: This study proposes a clinically guided approach and diagnostic algorithm for youth hypermobility, emphasizing precision medicine principles, while highlighting the urgent need for further research to identify hEDS biomarkers. Full article

This narrative review explores the integration of theranostics and artificial intelligence (AI) in neuro-oncology, addressing the urgent need for improved diagnostic and treatment strategies for brain tumors, including gliomas, meningiomas, and pediatric central nervous system neoplasms. A comprehensive literature search was conducted through PubMed, Scopus, and Embase for articles published between January 2020 and May 2025, focusing on recent clinical and preclinical advancements in personalized neuro-oncology. The review synthesizes evidence on novel theranostic agents—such as Lu-177-based radiopharmaceuticals, CXCR4-targeted PET tracers, and multifunctional nanoparticles—and highlights the role of AI in enhancing tumor detection, segmentation, and treatment planning through advanced imaging analysis, radiogenomics, and predictive modeling. Key findings include the emergence of nanotheranostics for targeted drug delivery and real-time monitoring, the application of AI-driven algorithms for improved image interpretation and therapy guidance, and the identification of current limitations such as data standardization, regulatory challenges, and limited multicenter validation. The review concludes that the convergence of AI and theranostic technologies holds significant promise for advancing precision medicine in neuro-oncology, but emphasizes the need for collaborative, multidisciplinary research to overcome existing barriers and enable widespread clinical adoption. Full article

Background/Objectives: Art therapy is a psychotherapeutic technique that involves the creation of tangible visual arts and represents a coping strategy to support children with cancer. Evaluating the effects of such activities on children with cancer is essential for providing evidence of the value that creativity holds within healthcare systems. A dedicated tool for assessing the creative process is the Arts Observational Scale (ArtsObS), focusing on mood and emotional states as key indicators of psychosocial well-being. This study aims to validate a translated version of the ArtsObS in the Italian language. Methods: The translation process followed recommendations for translation and cultural adaptation. The distribution properties of the scores, internal consistency, sensitivity to change, reliability, and convergent validity were assessed through observations conducted by two different evaluators. Results: The ArtsObS in its Italian adaptation is proven to be an adequate tool for capturing changes following an intervention, with good internal consistency and low sensitivity to differences between operators. The analysis supports the reliability of the ArtsObS across different observers. Conclusions: The Italian ArtsObS is a valid and reliable instrument for evaluating the impact of art therapy on pediatric patients’ mood and emotional states. It provides a standardized tool for clinical and research settings to assess creative interventions in pediatric oncology. Full article

Background/Objectives: Providing appropriate treatment for pediatric patients after traffic accidents remains a significant challenge. Furthermore, limited studies have validated the long-term effectiveness and safety of integrative Korean medicine treatment (IKMT) based on follow-up periods of 6 months or longer for pediatric patients. Methods: A retrospective chart review was conducted, focused on children aged 0–6 years who visited one of seven Korean medicine hospitals after traffic accident injuries and received IKMT between 1 January 2019 and 30 June 2023. The primary outcome was the Numeric Rating Scale (NRS) scores of chief complaints, and the secondary outcomes were quality of life, adverse events, and satisfaction with IKMT. Statistical analyses were conducted using paired t-tests and descriptive statistics, with a significance level of 5%. Results: Sixty-four participants were included in the retrospective chart review, and fifty-seven guardians responded to the surveys (mean age: 4.84 ± 1.26 years; mean duration of treatment: 19.20 ± 25.38 days). Among the immediate symptoms after the accidents, flashbacks and intrusive symptoms as well as nightmares and crying were the most common (50.9%). Following treatment, the NRS scores for flashbacks and intrusive symptoms and for nightmares and crying showed meaningful improvements from the time right after the accidents to the survey period. Follow-up confirmed that quality of life scores on all dimensions corresponded with those of healthy children. Nine adverse events were reported, and the participants fully recovered without the need for additional treatment. Furthermore, 91.2% of the survey respondents were satisfied with IKMT. Conclusions: IKMT was effective and safe for alleviating the post-accident symptoms in infants and young children aged 0–6 years involved in traffic accidents. Full article

Background/Objectives: Chronic pain and eating disorders are two prevalent and disabling pediatric health concerns, with serious, life-threatening consequences. These conditions can co-occur, yet little is known about best practices addressing comorbid pain and eating disorders. Delayed intervention for eating disorders may have grave implications, as eating disorders have one of the highest mortality rates among psychological disorders. Moreover, chronic pain not only persists but worsens into adulthood when left untreated. This study aimed to understand pediatric clinicians’ experiences with adolescents with chronic pain and eating disorders. Methods: Semi-structured interviews were conducted with hospital-based physicians (N = 10; 70% female; M years of experience = 15.3) and psychologists (N = 10; 80% female; M years of experience = 10.2) specializing in anesthesiology/pain, adolescent medicine/eating disorders, and gastroenterology across the United States. Audio transcripts were coded, and thematic analysis was used to identify key themes. Results: Clinicians described frequently encountering adolescents with chronic pain and eating disorders. Clinicians described low confidence in diagnosing comorbid eating disorders and chronic pain, which they attributed to lack of screening tools and limited training. Clinicians collaborated with and consulted clinicians who encountered adolescents with chronic pain and/or eating disorders. Conclusions: Results reflect clinicians’ desire for additional resources, training, and collaboration to address the needs of this population. Targets for future research efforts in comorbid pain and eating disorders were highlighted. Specifically, results support the development of screening tools, program development to improve training in complex medical and psychiatric presentations, and methods to facilitate more collaboration and consultation across health care settings, disciplines, and specialties. Full article

Introduction: Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infections in infants and children, as well as hospitalizations for respiratory infections in the pediatric population, representing a significant public health concern. Nirsevimab, a long-acting anti-RSV monoclonal antibody, has recently been approved by the European Medicines Agency (EMA). The aim of this study is to assess the utility of certain parameters, such as the Number Needed to Immunize (NNI), in supporting decision-makers regarding the introduction of nirsevimab as a universal prophylactic measure. Methods: A literature review was conducted to identify the definition and application of the NNI in the context of infectious disease prevention. The following online databases were consulted: Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library. The search was restricted to English-language texts published between 1 January 2000 and 30 January 2025. Results: The NNI represents the number of individuals who need to be immunized to prevent clinical outcomes such as medical visits and hospitalizations caused by infectious diseases. Six studies were identified that utilized this parameter to outline the benefits of immunization and describe the advantages of using monoclonal antibodies for RSV disease. Finelli and colleagues report that to prevent one RSV-related hospitalization, 37–85 infants aged 0–5 months and 107–280 infants aged 6–11 months would need to be immunized with long-acting anti-RSV antibodies. A recent study by Mallah et al. on the efficacy of nirsevimab estimates that the NNI required to prevent one RSV-related hospitalization is 25 infants. Studies by Francisco and O’Leary report NNI values of 82 and 128 infants, respectively, to prevent one RSV-related hospitalization with nirsevimab. Mallah et al. describe NNI as a metric useful to quantify the immunization effort needed to prevent a single RSV hospitalization. A recent Italian study reports that 35 infants need to be immunized to prevent one hospitalization due to RSV-LRTI and 3 infants need to be immunized to prevent one primary care visit due to RSV-LRTI. The studies indicate that the NNI for anti-RSV monoclonal antibodies is lower than the corresponding Number Needed to Vaccinate (NNV) for vaccines already included in national immunization programs. The main limitations of using this parameter include the absence of a shared threshold for interpreting results and the lack of consideration for the indirect effects of immunization on the population. Conclusions: The NNI is an easily understandable tool that can be used to convey the value of an immunization intervention to a variety of stakeholders, thereby supporting public health decision-making processes when considered in association with the uptake of the preventative strategy. At the current status, the estimated NNI of monoclonal antibodies against RSV results favourable and confirms the use in the first year of life for the prevention of RSV disease. Full article

This review explores the potential of magistral formulas (MFs) as a viable option to meet the needs of neonates, given the lack of adequate therapies for this vulnerable group. The scientific literature on medicines available for neonates is limited. The physiological differences between neonates and adults make it difficult to formulate these medicines. In addition, there are a variety of difficulties in conducting research on neonates: few clinical trials are performed, and there is frequent use of unauthorized medicines. Pharmacokinetics in neonates was investigated in comparison to adults, and different aspects of the absorption, distribution, metabolism, and excretion were observed. One of the main problems is the different pharmacokinetics between the two populations. It is necessary to promote and allow research related to pediatric drug design, approve a specific authorization for use in age-appropriate dosage forms, and improve the quality and availability of information on drugs. This study focused on the MFs typically used for pediatrics, specifically for neonates, analyzing the pharmaceutical forms currently available and the presence of indications and dosage recommendations of the European Medicines Agency. Medications were classified according to therapeutic group, as antihypertensives, corticosteroids, and antiepileptics. The use of off-label medicines remains high in neonatal intensive care units and in primary healthcare, besides in the preparation of MFs by pharmacists. The shortage of medicines specifically designed and approved for neonates is a serious problem for society. Neonates continue to be treated, on numerous occasions, with off-label medicines. Studies and research should be expanded in this vulnerable population group. Full article

Advances in molecular diagnostics have enabled precision medicine approaches in pediatric neuro-oncology, with small-molecule drugs emerging as promising therapeutic candidates targeting specific genetic and epigenetic alterations in central nervous system (CNS) tumors. This review provides a focused overview of several small-molecule agents under investigation or in early clinical use, including ONC201, tazemetostat, vorasidenib, CDK inhibitors, selinexor, and aurora kinase A inhibitors, among others. Highlighted are their mechanisms of action, pharmacokinetic properties, early efficacy data, and tolerability in pediatric populations. Despite encouraging preclinical and early-phase results, most agents face limitations due to study heterogeneity, lack of large-scale pediatric randomized trials, and challenges in drug delivery to the CNS. The review underscores the critical need for robust prospective clinical trials for the integration of these therapies into pediatric neuro-oncology care. Full article

Background/Objectives: Children with cancer suffer due to the underlying disease and prescribed cancer-directed therapies, and non-pharmacologic modalities may offer improved symptom control without additional medications. We sought to elicit knowledge, attitudes, and beliefs of Pediatric Hematology Oncology (PHO) providers surrounding the incorporation of acupuncture for symptom management for their patients. Methods: A cross-sectional survey instrument was created, formatted, and delivered to physicians and advanced practice providers (APPs) at a single US pediatric cancer center. Survey responses were summarized by descriptive statistics. Results: A total of 78 PHO clinicians participated (response rate 29%). Most participants were interested in learning more about acupuncture (n = 42, 56.0%), yet rarely (n = 17, 22.7%) or never (n = 46, 61.3%) recommend acupuncture to patients. Most (n = 51, 73.9%) noted that they would support institutional development of an acupuncture program. Over half (n = 37, 52.2%) indicated their threshold for minimum hematologic indices for acupuncture includes a platelet count greater than 20,000 and absolute neutrophil count (ANC) greater than 500 (n = 37, 54.4%). Approximately two-thirds (n = 52, 66.7%) of participants noted that acupuncture could improve their patient’s quality of life, and most (n = 46, 67.6%) were not worried about harm. Conclusions: Acupuncture for symptom management is an evidenced-based, guideline-concordant recommendation for adults with cancer, but robust data in the pediatric oncology population are lacking. PHO providers do not routinely recommend acupuncture for patients but note that it may improve quality of life. Given their high symptom burden, rigorous studies of non-pharmacologic strategies for pediatric symptom management are vital. Acupuncture should be examined as a potential beneficial adjunct. Full article

B-lineage acute lymphoblastic leukemia (B-ALL) is classified into more than 20 molecular subtypes, and next-generation sequencing has facilitated the identification of these with high sensitivity. Bulk RNA-seq analysis of bone marrow was realized to identify molecular subtypes in Mexican pediatric patients with B-ALL. High hyperdiploidy (27.3%) was the most frequent molecular subtype, followed by DUX4 (13.6%), TCF3::PBX1 (9.1%), ETV6::RUNX1 (9.1%), Ph-like (9.1%), ETV6::RUNX1-like (9.1%), PAX5alt (4.5%), Ph (4.5%), KMT2A (4.5%), and ZNF384 (4.5%), with one patient presenting both the PAX5alt and low hypodiploidy subtypes (4.5%). The genes TYK2, SEMA6A, FLT3, NRAS, SETD2, JAK2, NT5C2, RAG1, and SPATS2L harbor deleterious missense variants across different B-ALL molecular subtypes. The Ph-like subtype exhibited mutations in STAT2, ADGRF1, TCF3, BCR, JAK2, and NRAS with overexpression of the CRLF2 gene. The DUX4 subtype showed mutually exclusive missense variants in the PDGRFA gene. Here, we have demonstrated the importance of using RNA-seq to facilitate the differential diagnosis of B-ALL with successful detection of gene fusions and mutations. This will aid both patient risk stratification and precision medicine. Full article