Search Results (2,077)

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

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Pediatric palliative care (PPC) aims to enhance the quality of life of children with life-limiting conditions and their families through individualized, interdisciplinary support. Among this population, children with neurological diseases represent a substantial and growing group, often facing prolonged disease courses, cognitive impairment, and high prognostic uncertainty. Effective communication is central to PPC; however, it remains deeply influenced by cultural, religious, and spiritual frameworks that shape family perceptions of illness, suffering, and decision-making. This narrative review explores communication strategies in PPC, with a specific focus on children with neurological conditions, highlighting conceptual foundations, cross-cultural variations, and emerging best practices. Key findings highlight the importance of culturally humble approaches, family-centered communication models, and structured tools, such as co-designed advance care planning and dignity therapy, to enhance communication. Additionally, the review highlights the presence of ethical and interdisciplinary challenges, particularly in neonatal and neurology settings, where misaligned team messaging and institutional hesitancy may compromise trust and timely referral to palliative care. Future research, policy, and clinical education priorities should advocate for models that are inclusive, ethically grounded, and tailored to the unique trajectories of neurologically ill children. Integrating cultural competence, team alignment, and family voices is essential for delivering equitable and compassionate PPC across diverse care settings. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Amblyopia, commonly affecting children aged 0–6 years, results from disrupted visual processing during early development and often leads to reduced visual acuity in one eye. This study presents the development and preliminary usability assessment of a non-invasive ocular monitoring device designed to support oculomotor engagement and therapy adherence in amblyopia management. The system incorporates an interactive maze-navigation task controlled via gaze direction, implemented during monocular and binocular sessions. The device tracks lateral and anteroposterior eye movements and generates visual reports, including displacement metrics and elliptical movement graphs. Usability testing was conducted with a non-probabilistic adult sample (n = 15), including individuals with and without amblyopia. The System Usability Scale (SUS) yielded an average score of 75, indicating good usability. Preliminary tests with two adults diagnosed with amblyopia suggested increased eye displacement during monocular sessions, potentially reflecting enhanced engagement rather than direct therapeutic improvement. This feasibility study demonstrates the device’s potential as a supportive, gaze-controlled platform for visual engagement monitoring in amblyopia rehabilitation. Future clinical studies involving pediatric populations and integration of visual stimuli modulation are recommended to evaluate therapeutic efficacy and adaptability for early intervention. 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/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 5.92 mg/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment. Full article

Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare subtype of cutaneous T-cell lymphoma. It is characterized by the neoplastic infiltration of subcutaneous adipose tissue. Its clinical presentation, including subcutaneous nodules, fever, and systemic symptoms, often mimics inflammatory panniculitis, making diagnosis difficult. Case Presentation: This case report describes a 14-year-old female presenting with fever, limb pain, swelling, and subcutaneous nodules, who was ultimately diagnosed with SPTCL via punch biopsy and BIOMED-2 clonality assays, confirming positive T-cell receptor-γ chain gene rearrangement. Positron emission tomography–computed tomography revealed diffuse subcutaneous involvement across multiple body regions. Methylprednisolone and cyclosporine A treatment rapidly resolved her symptoms, with laboratory parameters, including ferritin and inflammatory markers, showing significant improvement. Next-generation sequencing identified a heterozygous C9 gene mutation (c.346C>T, p.Arg116Ter), adding a novel genetic dimension to the case. Following a tapered discontinuation of immunosuppressive therapy, the patient achieved sustained remission without relapse for over 1 year. Conclusions: We report a case of adolescent SPTCL treated with immunosuppressive therapy and suggest that immunosuppressive therapy should be considered before chemotherapy in pediatric patients with SPTCL but without HLH. 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/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article

Background and Objectives: A correct diagnosis of beta-hemolytic group A streptococcus (GAS)-pharyngitis allows the prevention of complications and unnecessary use of antibiotics. The aim of this study was to assess the management of pediatric GAS-pharyngitis in Romanian general practitioners (GPs)’ practice. Material and Methods: a cross-sectional study was conducted using a questionnaire distributed to Romanian GPs. Results: In total, 56 GPs completed the questionnaire, mostly females (83.9%, n = 47) from an urban area (60.7%, n = 34). They treated 5–10 (35.7%) or more than 10 (32.1%) cases of GAS monthly and considered white exudate on tonsils (92.9%, n = 52) to be the most suggestive clinical sign. Of the GPs, 25% (n = 14) used the Centor Criteria, 10.7% (n = 6) performed a rapid antigen detection test, and 42.9% (n = 24) requested throat culture for diagnosis. The younger GPs used the Centor Criteria significantly more often (p = 0.027) than the older ones. Most GPs (69.6%, n = 39) preferred targeted antibiotic therapy. Amoxicillin-clavulanate was the most commonly used antibiotic (55.4%, n = 31). Most GPs preferred oral antibiotics (89%, n = 50) for 10 days (55.4%, n = 31). Conclusions: Antibiotic treatment was initiated mostly based on clinical symptoms and in a short-course therapy. GPs stated that they prefer targeted antibiotic therapy, but they did not use proper diagnostic tools. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

Background and Clinical Significance: Traumatic dental injuries, particularly complicated crown fractures of permanent incisors, are common in adolescents, with maxillary central incisors most frequently affected due to their prominent position. These injuries, often resulting from sports or accidents, require prompt management to prevent complications such as pulp necrosis or infection, which can compromise long-term prognosis. Fragment reattachment offers a conservative, esthetically favorable approach when the fractured segment is intact, with outcomes comparable to composite restorations. This case report underscores the importance of timely intervention and advanced restorative techniques in pediatric dentistry. Case Presentation: A 16-year-old male presented with a complicated crown fracture of the upper left central incisor sustained during a soccer game. The fracture extended subgingivally with pulp exposure. The patient preserved the fragment in saline. Treatment involved fragment reattachment using a dentin bonding agent and flowable composite resin, followed by single-visit root canal therapy due to delayed presentation (48 h). A glass fiber post was placed to reinforce the restoration due to significant coronal loss. Three years of follow-up visits (1, 3, 6, 12, 24, and 36 months) revealed no clinical or radiographic complications, with the tooth remaining asymptomatic and functional. Conclusions: This case underscores the effectiveness of fragment reattachment when combined with meticulous technique and long-term monitoring. Full article