Search Results (2,069)

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Background/Objectives: Mumps remains a relevant vaccine-preventable disease globally, especially in settings where immunization coverage fluctuates or vaccine-induced immunity wanes. This study aimed to assess long-term trends in mumps incidence, vaccination coverage, clinical outcomes, and demographic characteristics in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia, over a 47-year period. Methods: We conducted a retrospective observational study using surveillance data from the Institute of Public Health of Vojvodina. Analyses included annual mumps incidence rates (1978–2024), coverage with mumps-containing vaccines (MuCVs; 1986–2024), monthly case counts, and individual-level case data for the 1997–2024 period. Variables analyzed included age, month of notification, gender, vaccination status, presence of clinical complications, and the method used for case confirmation. Results: Following the introduction of MuCV in 1986, the mumps incidence markedly declined, with limited resurgences in 2000, 2009, and 2012. Between 1997 and 2024, a total of 1358 cases were reported, with 62.7% occurring in males. Over time, the age distribution shifted, with adolescents and young adults being increasingly affected during the later (2011–2024) observed period. In 2012, the highest age-specific incidence was observed among individuals aged 10–19 and 20–39 years (49.1 and 45.5 per 100,000, respectively). Vaccination coverage for both MuCV doses was suboptimal in several years. The proportion of unvaccinated cases decreased over time, while the proportion with unknown vaccination status increased. Mumps-related complications—such as orchitis, pancreatitis, and meningitis—were rare and predominantly affected unvaccinated individuals: 84.2% of orchitis, 40.0% of pancreatitis, and all meningitis cases. Only two pancreatitis cases (40.0%) were reported after one MMR dose, while fully vaccinated individuals (two doses) had one orchitis case (5.3%) and no other complications. Laboratory confirmation was applied more consistently from 2009 onward, with 49.6% of cases confirmed that year (58 out of 117), and, in several years after 2020, only laboratory-confirmed cases were reported, indicating improved diagnostic capacity. Conclusions: Despite substantial progress in controlling mumps, gaps in vaccine coverage, waning immunity, and incomplete vaccination records continue to pose a risk for mumps transmission. Strengthening routine immunization, ensuring high two-dose MuCV coverage, improving vaccination record keeping, and enhancing laboratory-based case confirmation are critical. Consideration should be given to booster doses in high-risk populations and to conducting a seroepidemiological study to estimate the susceptible population for mumps in AP Vojvodina. 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

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy. 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

Background/Objectives: Anterior dental trauma in adolescents presents complex restorative challenges due to ongoing craniofacial development and high aesthetic expectations. This study evaluated the long-term clinical performance of feldspathic ceramic veneers and lithium disilicate crowns used in the anterior region following dental trauma in adolescents. Methods: A total of 209 restorations were placed in 85 adolescents (50 females, 35 males), aged 11.1–17.9 years (mean age: 15.1 years). Of these, 144 were lithium disilicate crowns, and 65 were feldspathic ceramic veneers. All restorations were fabricated using minimally invasive protocols and followed up for periods ranging from 3 to 60 months. Outcomes were assessed based on standardized clinical criteria for success and failure. Results: Lithium disilicate crowns exhibited superior long-term performance, with the majority of failures occurring in feldspathic veneers (p < 0.001), primarily due to chipping or structural fracture. Age and gender had no statistically significant influence on failure rates. Conclusions: Both feldspathic and lithium disilicate ceramic restorations represent viable treatment options for anterior dental trauma in adolescents. However, lithium disilicate demonstrates greater mechanical reliability, particularly in teeth with significant hard tissue loss. These results support the use of durable ceramic materials in adolescent restorative protocols involving dental trauma. Full article

Objectives: This study explored perceptions, experiences, and outcomes associated with the choice of insulin therapies among pediatric patients with type 1 diabetes mellitus (T1D). Methods: This study included 20 adolescents (8 male and 12 female) with T1D, with a mean age of 15.05 ± 0.91 years, a mean diabetes duration of 5.19 ± 1.2 years, and a mean most recent HbA1c of 7.03 ± 0.16%. Ten of the participants were using an insulin pump (n = 10) and another 10 had either refused (n = 7) or discontinued (n = 3) insulin pump therapy. A qualitative inductive method was employed, using in-depth individual interviews. The interview material was transcribed verbatim and grounded theory was used to analyze the verbal material. Results: Four main thematic categories were identified from the narrations that captured both common and divergent perceptions of insulin pump users versus non-users: (1) adjusting to the lifelong diagnosis, (2) exposing diabetes versus hiding it, (3) becoming autonomous and integrating insulin pump therapy into daily life, and (4) worrying over the pump. The third theme, capturing autonomy and integration, surfaced as the core thematic category of this study. Conclusions: This grounded theory study revealed that, by using insulin pump therapy, adolescent T1D patients can enhance their autonomy and facilitate the integration of insulin treatment into their life. This study identified processes that inform diabetes education and contribute to ameliorating gaps in the uptake and maintenance of pump therapy in pediatric care. Full article

Adolescence represents a critical period of neurodevelopment during which brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal survival and synaptic plasticity. While exercise-BDNF relationships are well-documented in adults, evidence in adolescents remains limited and inconsistent. This systematic review examined the effects of exercise modalities on circulating BDNF concentrations in adolescent populations. A systematic search was conducted following PRISMA guidelines across multiple databases (FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, Cochrane Library) through June 2025. Inclusion criteria comprised adolescents, exercise interventions, BDNF outcomes, and randomized controlled trial design. Methodological quality was assessed using the PEDro scale. From 130 initially identified articles, 8 randomized controlled trials were included, with 4 rated as excellent and the other 4 as good quality. Exercise modalities included aerobic, resistance, concurrent, high-intensity interval training, Taekwondo, and whole-body vibration, with durations ranging 6–24 weeks. Four studies demonstrated statistically significant BDNF increases following exercise interventions, four showed no significant changes, and one reported transient reduction. Positive outcomes occurred primarily with vigorous-intensity protocols implemented for a minimum of six weeks. Meta-analysis was not feasible due to high heterogeneity in populations, interventions, and control conditions. Moreover, variation in post-exercise sampling timing further limited comparability of BDNF results. Future research should standardize protocols and examine longer interventions to clarify exercise-BDNF relationships in adolescents. Full article

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

Background/Objectives: Borderline Personality Disorder (BPD) involves emotional dysregulation, interpersonal instability and impulsivity. Although treatments have advanced, evaluating the latest innovations remains essential. This rapid review aimed to (1) identify and classify recent therapeutic innovations for BPD, (2) assess their effects on clinical and functional outcomes, and (3) highlight research gaps to inform future priorities. Methods: Employing a rapid review design, we searched PubMed/MEDLINE, PsycINFO, and Embase for publications from 1 January 2019 to 28 March 2025. Eligible studies addressed adult or adolescent BPD populations and novel interventions—psychotherapies, pharmacological agents, digital tools, and neuromodulation. Two independent reviewers conducted screening, full-text review, and data extraction using a standardised form. Results: Sixty-nine studies—predominantly from Europe and North America—were included. Psychotherapeutic programmes dominated, ranging from entirely novel models to adaptations of established treatments (for example, extended or modified Dialectical Behavior Therapy). Pharmacological research offered fresh insights, particularly into ketamine, while holistic approaches such as adventure therapy and digital interventions also emerged. Most investigations centred on symptom reduction; far fewer examined psychosocial functioning, mortality, or social inclusion. Conclusions: Recent innovations show promise in BPD treatment but underserve the needs of mortality and societal-level outcomes. Future research should adopt inclusive, equity-focused agendas that align with patient-centred and recovery-oriented goals, supported by a coordinated, integrated research strategy. Full article

Due to technological advancements such as generative artificial intelligence (AI) and large language models, chatbots enable increasingly human-like, real-time conversations through text (e.g., OpenAI’s ChatGPT) and voice (e.g., Amazon’s Alexa). One AI chatbot that is specifically designed to meet the social-supportive needs of youth is Snapchat’s My AI. Given its increasing popularity among adolescents, the present study investigated whether adolescents’ likelihood of using My AI, as well as their positive or negative emotional experiences from interacting with the chatbot, is related to socio-demographic factors (i.e., gender, age, and socioeconomic status (SES)). A cross-sectional study was conducted among 303 adolescents (64.1% girls, 35.9% boys, 1.0% other, 0.7% preferred not to say their gender; M_age = 15.89, SD_age = 1.69). The findings revealed that younger adolescents were more likely to use My AI and experienced more positive emotions from these interactions than older adolescents. No significant relationships were found for gender or SES. These results highlight the potential for age to play a critical role in shaping adolescents’ engagement with AI chatbots on social media and their emotional outcomes from such interactions, underscoring the need to consider developmental factors in AI design and policy. Full article

This study assessed the effects of a family function (FF) program on excessive digital behaviors—smartphone overuse (SO) and phubbing—and psychological needs—anxiety, loneliness, and fear of missing out (FoMO)—among 28 Thai female Muslim adolescents randomly assigned to the experimental (M_age = 15.7) and control (M_age = 15.2) groups. The experimental group received two 1.5 h morning sessions of the FF program weekly over four weeks (eight sessions in total). Baseline assessments confirmed group homogeneity. Using repeated-measures ANOVA with Bonferroni correction (p < 0.008), the results indicated a significant improvement in family function for the intervention group (F (1,26) = 11.91, p = 0.002, η²_p = 0.31), with a strong time-by-group interaction (F (1,26) = 19.51, p < 0.001, η²_p = 0.43). While the program did not significantly reduce SO overall, a notable interaction effect suggested group differences (F (1,26) = 10.31, p = 0.004, η²_p = 0.28). Phubbing remained unaffected. For psychological outcomes, interaction effects were found for the FoMO (F = 10.00, p = 0.004) and loneliness (F = 8.67, p = 0.007), though no main effects emerged. Anxiety levels did not significantly change after correction. These findings suggest that the program effectively enhances family functioning and partially alleviates psychosocial risks, but further refinements are needed to address digital overuse and anxiety more effectively. Full article

Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article

Background/Objectives: Biofeedback interventions are increasingly utilized in pediatric and adult care, with evidence in treating specific medical conditions and specific symptoms. However, evidence supporting their efficacy among children and adolescents and young adults (AYAs, aged 15–39) with cancer is limited. The aims of this systematic review are to present, assess, and synthesize the existing research on biofeedback in pediatric and AYA oncology, identify gaps in biofeedback research within this population, and provide recommendations for future research and clinical implications. Methods: A systematic search for articles was conducted using six bibliographic databases—PubMed/MEDLINE (NLM), EMBASE (Elsevier), CINAHL (EBSCO), SPORTDiscus (EBSCO), PsycINFO (OVID), and PEDro (NeuRA)—with an update on 5/7/2025. Included were studies involving pediatric/AYA oncology participants (0–39 years old) and those receiving at least one biofeedback modality. The methodological quality and risk of bias among included articles were assessed using the Cochrane Risk of Bias (ROB) Tool (modified version for non-randomized studies). A narrative synthesis of included studies examined the type of cancer studied, type of biofeedback used, study designs and methodological quality, and key outcomes evaluated. Results: While the literature suggests that biofeedback may offer beneficial outcomes for managing various pediatric/AYA oncology-related symptoms, such as pain, anxiety, and fatigue, only 8 studies out of 1013 screened (<1%) met inclusion criteria. Limitations included low study quality (small sample sizes, lack of control groups, and methodological inconsistencies). Conclusions: While biofeedback shows promise as a feasible and effective intervention, there is a call to action for well-designed, methodologically rigorous studies to substantiate its effectiveness and inform evidence-based practice specifically for pediatric/AYA oncology patients and clinicians. Full article