Search Results (3,691)

Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article

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

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

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: The diagnosis of pediatric dental conditions from panoramic radiographs is uniquely challenging due to the dynamic nature of the mixed dentition phase, which can lead to subjective and inconsistent interpretations. This study aims to develop and rigorously validate an advanced deep learning model to enhance diagnostic accuracy and efficiency in pediatric dentistry, providing an objective tool to support clinical decision-making. Methods: An initial comparative study of four state-of-the-art YOLO variants (YOLOv8, v9, v10, and v11) was conducted to identify the optimal architecture for detecting four common findings: Dental Caries, Deciduous Tooth, Root Canal Treatment, and Pulpotomy. A stringent two-tiered validation strategy was employed: a primary public dataset (n = 644 images) was used for training and model selection, while a completely independent external dataset (n = 150 images) was used for final testing. All annotations were validated by a dual-expert team comprising a board-certified pediatric dentist and an experienced oral and maxillofacial radiologist. Results: Based on its leading performance on the internal validation set, YOLOv11x was selected as the optimal model, achieving a mean Average Precision (mAP50) of 0.91. When evaluated on the independent external test set, the model demonstrated robust generalization, achieving an overall F1-Score of 0.81 and a mAP50 of 0.82. It yielded clinically valuable recall rates for therapeutic interventions (Root Canal Treatment: 88%; Pulpotomy: 86%) and other conditions (Deciduous Tooth: 84%; Dental Caries: 79%). Conclusions: Validated through a rigorous dual-dataset and dual-expert process, the YOLOv11x model demonstrates its potential as an accurate and reliable tool for automated detection in pediatric panoramic radiographs. This work suggests that such AI-driven systems can serve as valuable assistive tools for clinicians by supporting diagnostic workflows and contributing to the consistent detection of common dental findings in pediatric patients. 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

Periodontal diseases in pediatric subjects represent a challenging and relatively underexplored area compared to the extensive data available about periodontal diseases in adults. The present narrative review aims to explore the periodontal status and the related subgingival and/or salivary microbial profiles in pediatric subjects (≤18 years), focusing also on the state of health or systemic diseases. In healthy periodontium, early colonizers, such as Streptococcus and Actinomyces spp., dominate the subgingival microbiota, supporting an eubiosis state. Low levels of Candida albicans and latent Herpesviridae may be detected. In gingivitis, the microbial profile shifts towards more pathogenic species, including Prevotella intermedia and Fusobacterium nucleatum. In necrotizing gingivitis, typically affecting systemically compromised children, the microbial profile is characterized by spirochetes, Fusobacterium, and Prevotella intermedia. Viral coinfections—especially with HSV, CMV, and EBV—are more frequently detected. In periodontitis, the microbiota was dominated by red complex pathogens along with Aggregatibacter actinomycetemcomitans in the aggressive forms, especially in systemically compromised children, as Herpesviridae reactivation and co-infections. Fungal involvement is less well characterized; Candida albicans may be present, particularly in cases of severe immune suppression. Nevertheless, the lack of pediatric longitudinal studies investigating periodontal disease progression after periodontal treatment and related changes in microbiological composition limited the understanding and exploration of the oral microbiota over time. 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: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. 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