Search Results (204)

Neuroblastoma is the most common extracranial solid tumor of childhood and remains a leading cause of cancer-related mortality in pediatric patients. Characterized by marked clinical and biological heterogeneity, the disease ranges from spontaneously regressing tumors in infants to highly aggressive, treatment-resistant malignancies in older children. Advances in molecular biology and genomics have significantly improved understanding of neuroblastoma pathogenesis, revealing the critical role of genetic and epigenetic alterations—such as MYCN amplification, ALK mutations, and chromosomal aberrations—in disease behavior and prognosis. Contemporary risk stratification systems now integrate clinical, biological, and molecular features to guide therapy more precisely. Management strategies have evolved toward risk-adapted, multimodal approaches. Low- and intermediate-risk patients often achieve excellent outcomes with surgery alone or limited chemotherapy, whereas high-risk neuroblastoma requires intensive multimodal treatment including induction chemotherapy, surgical resection, high-dose chemotherapy with autologous stem cell rescue, radiotherapy, and maintenance therapy. The incorporation of immunotherapeutic approaches, particularly anti-GD2 monoclonal antibodies, has significantly improved survival in high-risk disease. Emerging therapies such as targeted agents, radiopharmaceuticals, and cellular immunotherapies are further expanding the therapeutic landscape. Despite these advances, high-risk and relapsed neuroblastoma remain associated with substantial morbidity and mortality. Ongoing challenges include treatment resistance, long-term toxicity, and disparities in access to advanced therapies. Continued progress will depend on integrating molecular profiling into clinical decision-making, refining risk-adapted treatment strategies, and expanding international collaborative research efforts. This narrative review summarizes current knowledge on neuroblastoma epidemiology, biology, staging, and treatment, highlighting recent advances and future directions aimed at improving outcomes for affected children. Full article

Parents have a major influence on a child’s wellbeing, including the development of internalizing problems in their children. Furthermore, the influences between parents and their children could be reciprocal. This study examined the longitudinal, reciprocal association between maternal aggravation and child internalizing problems from childhood to adolescence and the potential mediating role of maternal verbal aggression. Using a sample of approximately 5000 mothers across four waves from the Future of Families & Child Wellbeing Study (FFCWS), results from a cross-lagged autoregressive model suggested that maternal aggravation was related to child internalizing problems from childhood to adolescence, whereas child internalizing problems were related to maternal aggravation only during early childhood. No mediation effect through maternal verbal aggression was found. Taken together, these findings highlight the long-term and direct impact of maternal aggravation on child internalizing problems, which has important implications for family researchers and practitioners. Full article

The World Health Organization (WHO) and International Consensus Classification (ICC) systems have classified EBV-positive NK/T-cell neoplasms in adults and EBV-positive T/NK-cell lymphoid lymphoproliferative disorders (LPD) in children. Recent molecular profiling techniques have revealed the pathogenesis of these disorders, showing interactions among EBV-encoded proteins, host immune responses, and genetic alterations. Extranodal NK/T-cell lymphoma (ENKTL) shows molecular diversity, with various subtypes (TSIM, MB, and HEA) identified through a multiomics approach. Aggressive NK-cell leukemia (ANKL) has mutations in JAK/STAT, epigenetic regulators, and TP53 pathways. EBV-positive nodal T- and NK-cell lymphoma (ENTNKL) is a new entity, distinguished by primary nodal presentation and a unique molecular profile. Severe mosquito bite allergy (SMBA), hydroa vacciniforme lymphoproliferative disorder (HVLPD), and systemic chronic active EBV disease (CAEBV) are rare childhood EBV-driven LPDs defined by clinico-pathologic criteria, with largely unexplored genomic landscapes. Studies of CAEBV samples have found ENKTL-like driver mutations, including DDX3X and KMT2D, in EBV-infected NK/T cells, while KMT2D and chromatin modifier mutations were common in HVLPD. Comprehensive molecular sequencing of SMBA and Systemic EBV-positive T-cell lymphoma of childhood remains lacking. These findings suggest all EBV⁺ NK/T-cell LPDs exist on a biological continuum of viral oncogenesis. The integration of clinical, pathological, and molecular information aims to create a more accurate classification system, enabling better risk evaluation and tailored treatment strategies for patients with these complex disorders. Full article

The prevalence and incidence of prediabetes in children and youth continue to increase in parallel with the obesity epidemic. While prediabetes is defined by elevated HbA1c and/or impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), the risk of clinical disease is a continuum. Individuals with prediabetes are at a higher risk of developing youth-onset type 2 diabetes, which is considered a more aggressive form of the disease. This condition is associated with increased cardiovascular and metabolic risks and leads to an earlier onset of complications compared to adults with type 2 diabetes. Additionally, significant damage to beta cells may occur even before dysglycemia develops. Recent data indicate that mortality rates are higher in youths with type 2 diabetes compared to those with type 1 diabetes. Childhood prediabetes and cardiovascular complications associated with it are a significant health concern. This review provides the latest insights into this complex issue. We will present an overview of pathophysiology, screening methods, and therapeutic options to prevent the progression from prediabetes to type 2 diabetes in children. In summary, it is crucial to identify prediabetes in children, as this underscores the importance of appropriate screening and timely intervention. Full article

Social competence in early childhood is a foundational, multifaceted construct and a strong predictor of academic and behavioral outcomes. Difficulties in this domain are often linked to challenges in forming positive peer relationships. The present study investigates the association between children’s social competence and peer exclusion, while examining the effect of gender in both domains. Participants were 312 children (3–5 years old) from 39 early childhood education and care classrooms in Greece. Construct validity for the adapted version of the Social Behavior Scale was initially established, supporting its proposed three-dimensional structure, comprising emotional competence, social engagement, and aggressiveness. Measurement equivalence across gender was also confirmed at all levels. Structural Equation Modeling revealed moderate associations between peer exclusion and two dimensions of social competence (i.e., emotional competence and aggressiveness). Gender effects were identified only for aggressiveness, with boys exhibiting slightly higher levels of aggressive behavior. Mediation analysis further revealed that gender exerted an indirect effect on peer exclusion through aggressiveness. The findings highlight the importance of addressing specific behavioral patterns, rather than gender alone, when designing interventions to foster positive peer relations and support children’s social development in early childhood education and care. Full article

Background and Objectives: Retinopathy of prematurity (ROP) remains a leading cause of preventable childhood blindness, with its severity influenced by a complex interaction between nutritional status, metabolic maturation, and systemic vulnerability. This study aimed to evaluate whether early nutritional patterns and serum metabolic parameters, including hepatic and renal biomarkers, are associated with ROP severity and whether they may serve as potential predictors of disease progression. Materials and Methods: We conducted a retrospective study on 140 preterm infants, totaling 280 eyes, admitted between 2021 and 2024 in two neonatal intensive care units (NICU). Each eye was analyzed independently according to International Classification of Retinopathy of Prematurity (ICROP) criteria. Data on the timing of enteral feeding, duration and type of nutrition, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, blood glucose, urea and creatinine were collected throughout the first 28 days of life. Statistical analysis included Kruskal–Wallis and Chi-square tests, with a significance threshold of p < 0.05. Results: ROP was identified in 53.57% of cases. Enteral feeding began earlier in infants without ROP, whereas delayed initiation and prolonged parenteral nutrition were associated with more advanced stages. Natural feeding decreased with increasing severity and was absent in aggressive retinopathy of prematurity (A-ROP). Severe disease stages showed higher AST, ALT, urea and creatinine levels, along with lower early total protein values. Glycemic instability was observed more frequently in stage 2 and stage 3. Conclusions: Early nutritional support, especially early enteral feeding and natural feeding, appears protective against ROP progression. Hepatic, renal and glycemic metabolic changes are closely correlated with disease severity, indicating that metabolic balance reflects overall vulnerability in preterm infants. Incorporating nutritional and metabolic assessment into routine screening may enhance early risk identification and optimize clinical monitoring. Full article

Background: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that shares histological features with Kaposi’s sarcoma. It usually occurs in infancy or early childhood and is seldom reported in adults. The most common sites are the skin and retroperitoneum, whereas the head, neck, and mediastinum are less frequently involved. KHE rarely regresses spontaneously, and metastasis is uncommon, but up to 70% of cases may develop Kasabach–Merritt Syndrome (KMS), a life-threatening coagulopathy. Here, we present an unusual case of KHE in an adult patient, emphasizing the importance of early recognition and management. Methods: A 39-year-old woman with systemic lupus erythematosus presented with an exophytic lesion in the left retromolar region. Clinical and radiological evaluations were followed by both incisional and excisional biopsies. Histopathological and immunohistochemical analyses were performed, and surgical resection with wide margins was undertaken according to recommendations from a multidisciplinary tumor board. Results: Histology revealed spindle cell clusters, slit-like vascular spaces, endothelial cells with eosinophilic cytoplasm, and immunopositivity for CD31, CD34, and smooth muscle actin, confirming the diagnosis of KHE. Given the tumor’s locally aggressive behavior and potential risk of KMS, extended surgical excision was performed. Conclusions: This case underscores the diagnostic challenges of KHE in adults and highlights the essential role of histopathology, immunohistochemistry, and multidisciplinary evaluation. Prompt diagnosis and radical surgical management are critical to preventing complications and improving patient outcomes. Full article

Melanoma is a highly aggressive skin cancer primarily linked to ultraviolet (UV) radiation. However, the potential role of ionizing radiation from radiotherapy in melanoma development remains unclear. This review synthesizes data from epidemiologic studies and case reports on melanoma after radiation exposure. Evidence indicates that childhood radiotherapy, even at low doses, is associated with an increased melanoma risk, plausibly reflecting the heightened radiosensitivity of developing melanocytes. Occupational radiation exposure, particularly in earlier eras with insufficient shielding, also appears to elevate risk. In patients exposed to radiation in adulthood, findings are mixed: large population datasets suggest a modest increase in melanoma following therapeutic radiation, whereas some case–control analyses do not demonstrate a clear dose–response relationship. UV radiation promotes melanomagenesis through direct DNA photoproducts driving characteristic C>T transitions at dipyrimidine sites, alongside oxidative stress and local immune modulation that facilitate malignant transformation. Collectively, individuals with prior radiotherapy, especially those irradiated in childhood, should be considered at increased melanoma risk and may benefit from long-term, targeted surveillance of irradiated fields. Awareness of this association between radiation exposure and melanoma may also support clinicopathologic correlation during the diagnostic evaluation of melanocytic lesions. Future work should define dose–response relationships in contemporary radiotherapy methods, characterize molecular signatures of ionizing radiation-associated melanomas, and establish evidence-based surveillance strategies for high-risk cohorts. Full article

The escalating exposure of young children to digital gaming necessitates a critical examination of its behavioral impacts. However, evidence regarding its influence on aggressive behavior remains limited. This study investigated the relationship between digital play addiction tendency and our dimensions of aggression: physical aggression, relational aggression, self-directed aggression, and aggression against objects. This study employed a cross-sectional design, gathering data through parent assessments. The sample consisted of 744 children aged 4 to 6 years. The average age of the participants was 33.5, with 82% of the sample being female. The participants came from a lower (27%), middle (37%), and high (36%) socioeconomic background. The data were analyzed using a Structural Equation Modeling (SEM) approach to test the hypothesized relationships. The main findings from the SEM analysis indicated that a higher digital play addiction tendency was a significant positive predictor of all four dimensions of aggression. These results highlight the potential adverse effects of digital play addiction tendency on the development of maladaptive behaviors in early childhood. This study underscores the urgent need to develop strategies that foster healthier digital media consumption and mitigate the adverse effects of digital gaming on children’s developmental outcomes. Full article

Background: Wolf–Hirschhorn syndrome (WHS) is a rare contiguous gene deletion disorder associated with a high incidence of early-onset epilepsy. Despite the clinical relevance of seizures in this population, few large-scale studies have provided detailed data on epilepsy phenotypes and treatment outcomes. Methods: We analyzed a cohort of 140 individuals with WHS from Spain and Latin America. Using validated caregiver-reported questionnaires, we collected detailed information on seizure types, antiseizure medications (ASM) use, and associated comorbidities. Statistical comparisons were made to identify correlations between epilepsy severity, deletion size, and functional outcomes. Results: Epilepsy was observed in 92% of patients, typically beginning before 12 months of age. Multiple seizure types were common, particularly generalized tonic–clonic and atypical absence seizures. Status epilepticus occurred in 58% of cases, with a high proportion requiring multiple ASMs. Valproic acid and levetiracetam were the most commonly used treatments. Patients with more severe epilepsy tended to have larger deletions (>9 Mb) and poorer developmental outcomes. ASM discontinuation was significantly associated with older age at evaluation, supporting improved seizure control over time. Conclusions: Epilepsy in WHS is frequent, often severe in early childhood, and associated with neurodevelopmental impairment and increased treatment burden. While some patients show improvement with age, early aggressive management using appropriate ASMs may be critical to improve neurological prognosis. Advances in diagnosis, early intervention, and targeted therapies offer hope for improved long-term outcomes in this vulnerable population. Full article

Parental adverse childhood experiences (ACEs) are linked to negative outcomes in children, including emotional and behavioral problems, developmental delays, and higher risk for psychopathology. Most research focuses on school-aged children or community samples, with few studies examining preschool-aged children in child psychiatric care. Understanding parental ACEs in this population is crucial, as early childhood is a sensitive developmental period, and intergenerational effects may be particularly pronounced in children already presenting with psychiatric symptoms. Background/Objectives: The goal of this study was to analyze how parents of patients in an early childhood (0–5.9 yrs) mental health outpatient clinic differ from the general population in terms of the frequency of ACEs. In addition, we investigated the connection between mental health disorders in young children and the specific ACE scores of their parents. Methods: A total of 116 caregivers (34.45 years (SD = 5.28)) and their children (71.6% boys, 28.4% girls) at an average age of 3.99 years (SD = 1.35, range = 0.31–5.95) were included in the analysis. The legal guardians completed the 10-item ACE questionnaire. The young children were diagnosed as part of outpatient treatment using the DC:0–5 classification system. We analyzed the ACE scores and diagnoses descriptively and in comparison to a community sample. Results: An average value of 2.38 parental ACEs was reported by our sample, and 68.1% (n = 79) reported at least one ACE. The high-risk group with four or more ACEs comprised 30.2% (n = 35). The most common diagnosis in young children was the Disorder of Dysregulated Anger and Aggression of Early Childhood, followed by global developmental delay. Adjustment disorder was third in terms of frequency. Among the examined child psychiatric diagnoses, adjustment disorder showed a significant correlation with parents being affected by the ACE category of neglect (OR = 2.54; 95% CI: 1.012–6.369; p = 0.047). Conclusions: Parents who presented their children at an early childhood mental health outpatient clinic reported significantly more ACEs as compared to representative data on ACEs in adulthood. These results highlight the need for further studies with larger samples to enable a more in-depth analysis of the general intergenerational transmission processes and the differential transmission of specific ACEs to specific diagnoses in preschool-aged children. Full article

The contemporary world presents increasingly complex challenges for adolescents. In addition to normative developmental tasks, adolescents must now navigate epidemic health crises, armed conflicts, family dissolution, economic instability, and academic pressures. Consequently, adolescents experience diminished security and elevated levels of anxiety, loneliness, and depression. While the need for emotional support has intensified across all demographics, adolescents’ psychological needs remain particularly underserved. The American Psychological Association has recently advocated for the expansion of group therapy services, a format that aligns particularly well with adolescents’ socioemotional needs, serving as a developmental bridge from childhood to adulthood. Research on adolescents’ group legs much behind the adult literature. The aim of the current paper is to show the potential power of group therapy with adolescents based on a selective review of our empirical studies examining the impact of therapy groups on adolescents’ well-being. The reviewed papers encompass randomized controlled trials and process research identifying critical therapeutic factors, collectively establishing the intervention’s validity. Results demonstrate the superiority of these groups compared to non-treatment controls and equivalence to individual therapy in reducing stress, anxiety, and aggression while enhancing self-perception, self-control, and academic functioning. These findings support the conclusion that group psychotherapy significantly contributes to adolescent well-being. Considering adolescents’ high yet unmet need for emotional support, group therapy appears to be a valid alternative. Full article

Acute myeloid leukemia (AML) accounts for 15–20% of childhood leukemia cases; however, it is characterized by very high aggressiveness and has the highest mortality rate among leukemias, with relapse rates ranging from 34% to 38%. It is a disease characterized by high molecular diversity, and the frequency of specific genetic alterations in children is different from that in adults. Furthermore, mutations and rearrangements vary with age within the pediatric population. To date, a wide spectrum of genetic alterations has already been studied, but the molecular landscape of each patient is unique. An analysis of rearrangements and mutations specific to children of different ages appears to be crucial in order to individualize diagnosis and therapy appropriately. The aim of the following review is to analyze the molecular landscape of pediatric AML by age in detail in order to prioritize therapeutic strategies dedicated to specific age groups. Full article

Background: Preschool bedroom television placement represents an established risk factor for negative psychological and behavioral outcomes in adolescence. Girls and boys have different risk factors for developmental psychopathology. It is unclear if childhood sport participation can act as a protective factor for the potential maladaptive behaviors associated with having a bedroom television in early childhood. Methods: This study aims to evaluate the impact of having a bedroom television in early childhood on later externalizing behaviors while examining the potential beneficial role of extracurricular sport participation in middle childhood using the Quebec Longitudinal Study of Child Development (Canada). We examine subsequent teacher-reported psycho-social outcomes by the end of sixth grade. Linear regression is used to examine the interaction between child-reported bedroom television placement (age 4 years) and parent-reported childhood sport participation trajectories (ages 6 to 10 years) in predicting behavioral outcomes at age 12 years. Results: For boys, extracurricular sport amplified the relationship between having a preschool bedroom television and subsequent physical aggression (b = 0.95, SE = 0.32, p < 0.001) and ADHD symptoms (b = 0.59, SE = 0.30, p ≤ 0.05), beyond individual and family characteristics. No interaction results were found for girls; however, consistent sport participation between ages 6 and 10 years resulted in a decrease in ADHD symptoms in girls (b = −0.329, SE = 0.102, p ≤ 0.001). Conclusion: Unexpectedly, for boys exposed to early bedroom television, consistently participating in extracurricular sport in childhood exacerbated long-term behavioral risks. Social unpreparedness from bedroom television placement countered the intended benefits of sport. This private access to screens might influence sedentary, unsupervised, isolated activity that increases the chances of viewing violence and reduces opportunities for social interaction. Full article