Search Results (1,073)

Background: Residential wood combustion (RWC) is a major local source of fine particulate matter (PM_2.5) in Nordic regions. We quantified the health impacts and economic costs of long-term exposure to PM_2.5 from RWC in Västerbotten County, northern Sweden. Methods: High-resolution annual mean concentrations of PM_2.5 from small-scale residential heating in 2023 were obtained from a national dispersion-modelling system. Population-weighted exposure was calculated by combining grid-level concentrations with home address coordinates for the resident population. Health impact assessment (HIA) followed the framework used in Nordic studies and the VALESOR project, applying a near-source PM_2.5–mortality exposure–response function with a relative risk of 1.26 per 10 µg/m³ for natural-cause mortality and VALESOR default functions for morbidity (ischaemic heart disease, stroke, COPD, lung cancer, type 2 diabetes, dementia, childhood asthma, cardiovascular hospital admissions). Attributable cases and years of life lost (YLL) were estimated, and the economic valuation used VALESOR unit costs for Sweden to derive central, low and high damage-cost estimates. Results: The population (n = 280,742)-weighted mean RWC-PM_2.5 exposure was 0.16 µg/m³ (interquartile range 0.10–0.21). This was associated with an estimated 30 years of life lost (YLL) per year from natural-cause mortality, plus incident morbidity of approximately 0.3 lung cancer cases, four childhood asthma cases, three COPD cases, three IHD events, one stroke, two dementia cases, one diabetes case and 0.8 cardiovascular hospital admissions annually. The total annual health-related cost attributable to RWC-PM_2.5 was about €7.0 million (95% uncertainty range €4.6–9.4 million), dominated by mortality and disutility costs. Conclusions: PM_2.5 concentrations from residential wood burning are associated with health impacts costing multi-million Euros in a Nordic region, supporting policies to reduce emissions from residential wood heating and to promote cleaner heating alternatives. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies. Full article

Background/Objectives: Actinic keratosis is an intraepithelial lesion that may progress into squamous cell carcinoma; therefore, all lesions should be treated. The study aimed to investigate the potential correlations between patient and lesion characteristics, treatment option choice, and clinical outcomes, analyzing long-term real-world data. Methods: A retrospective study was conducted in a specialized hospital in Milan. Data on patients with actinic keratoses were collected from January 2018 to July 2024. Results: A total of 369 patients were included, with normal weight (58%), higher educational level (83%), personal skin cancer history (51%), childhood sunburns (68%), and face localization (70%), with multiple contiguous distribution (54%) of lesions. In total, 45.5% received multiple treatments. Field-directed therapies were prescribed in 84% of cases (32% of complete clearance). A total of 43% were lost to follow-up. Higher educational level, personal and familiar skin cancer history, previous atypical naevus excision, higher naevus count, and multiple treatments (p < 0.05) were associated with regularity in visit attendance. In multivariable analysis, immunosuppression (OR = 5.01 [0.97, 29.5], p = 0.056) and multiple contiguous lesions (OR = 4.62 [1.75, 14.7], p = 0.004) were found to be significantly associated with incomplete clinical response. Conclusions: Real-world data on patients with actinic keratoses may help identify more personalized management strategies that influence treatment outcomes and adherence to follow-up. Full article

Background/Objectives: Survival in children, adolescents and young adults (CAYA) with bone sarcoma remains inferior to that of many other early-life cancers. Early recognition and treatment initiation may reduce the risk of presenting with advanced disease. We aimed to synthesize evidence on five predefined diagnostic intervals, separately synthesize pathway-specific intervals, and identify factors associated with diagnostic interval duration. Methods: A systematic review was conducted according to PRISMA guidelines. We included studies reporting the duration of a diagnostic interval in at least five patients aged 0–39 years with primary bone sarcomas, including osteosarcoma, Ewing sarcoma, and less common histological subtypes. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus were searched for studies published between 2000 and 2025. Risk of bias was assessed using a custom domain-based tool. Results: Twenty-nine studies including 9271 patients from high-income countries met the inclusion criteria. Substantial heterogeneity in study design, populations, and interval reporting precluded meta-analysis. Reported median intervals were patient intervals of 13–84 days, diagnostic intervals of 15–123 days, total diagnostic intervals of 28–150 days, treatment intervals of 7–24 days, and total intervals of 66–88 days. Older age within the CAYA population and axial tumor location were the factors most consistently associated with longer diagnostic intervals. No consistent association between diagnostic interval duration and survival was identified. Pathway-specific intervals provided additional insight into different components of the diagnostic pathway, particularly after initial healthcare contact, although evidence remained limited. Conclusions: Diagnostic interval durations varied substantially across studies, reflecting methodological heterogeneity and differences in diagnostic pathways. Standardized prospective studies are needed to strengthen the evidence base. Full article

Endocrine-disrupting pesticides (EDPs) are environmental toxicants capable of perturbing hormonal homeostasis through multiple molecular and cellular mechanisms. Growing evidence indicates that these compounds contribute to a broad spectrum of adverse health outcomes extending beyond classical endocrine dysfunction. This review critically synthesizes current knowledge on the toxicological mechanisms of EDPs and evaluates epidemiological evidence linking exposure to human disease. Mechanistically, EDPs act through modulation of nuclear hormone receptors, disruption of membrane-associated signaling pathways, interference with hormone synthesis, metabolism, and transport, induction of oxidative stress and mitochondrial dysfunction, and epigenetic reprogramming. These molecular events converge on shared biological pathways that affect multiple organ systems and life stages. Human and experimental evidence associates EDP exposure with reproductive dysfunction, endocrine-related cancers, metabolic disorders, thyroid abnormalities, and neurodevelopmental impairments. Particular concern surrounds exposure during critical windows of susceptibility, especially prenatal development and early childhood, when endocrine systems are highly vulnerable to disruption and developmental programming. Across disease endpoints, recurring mechanisms, including endocrine receptor perturbation, oxidative stress, inflammation, and epigenetic alterations, support a unifying toxicological framework linking diverse adverse outcomes. Despite substantial progress, important uncertainties remain regarding chronic low-dose exposure, non-monotonic dose–response relationships, cumulative effects of pesticide mixtures, and the translation of mechanistic findings into human risk assessment. Future research should integrate repeated biomonitoring, advanced mixture modeling, mechanistic biomarkers, and multi-omics approaches within longitudinal life-course studies. Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide. Full article

Diffuse midline glioma, H3K27-altered (DMG) is a group of central nervous system (CNS) tumors with no curative treatment options. First described in the early 20th century, prognosis and clinical outcome for patients have changed very little, and the only standard treatment modality remains radiation therapy. The development of targeted therapies against DMG has long been hindered due to the paucity of tumor tissue and disease models for laboratory research. However, access to patient-derived tumor tissue and the subsequent establishment of DMG preclinical models in recent years has led to a deeper understanding of underlying disease mechanisms and aided the development of novel therapeutic agents. Here, we provide an overview of newly established DMG modeling systems in the preclinical setting leading toward immunotherapy clinical trials for patients with DMG. Full article

Cancer predisposition syndromes (CPSs) account for 8.5–18% of all childhood cancer cases. Most of them are inherited in an autosomal dominant pattern; consequently, there is a 50% risk of transmission to offspring. Early detection of CPSs is crucial for choosing patient treatment strategies and for counseling in the family. This study enrolled 886 pediatric patients with hematologic and solid neoplasms from prospective and retrospective cohorts (2018–2025). Clinical exome or multigene panel sequencing was used to analyze blood DNA. Overall, 186 pathogenic/likely pathogenic (PLP) variants in cancer-associated genes were identified in 176/886 (20%) of patients, and the most frequently mutated were the NF1 (n = 35) and TP53 (n = 18) genes. Among the 186 PLP variants, 126/886 (14.2%) were causative for pediatric neoplasms, while 56/886 (6.3%) were heterozygous mutations associated with adult-onset CPSs affecting DNA repair. The highest total mutation rate was revealed in retinoblastoma (80%), peripheral nerve sheath tumors (60%), and pheochromocytoma/paraganglioma (47%), while the lowest rate was found in hematologic malignancies (4.6%) and neuroblastoma (12%). The wide range and high frequency of deleterious variants in pediatric patients, especially in those with solid tumors, highlights the importance of multigene panel sequencing for the accurate determination of CPSs. Full article

Background and Clinical Significance: Varicella, caused by the varicella-zoster virus (VZV), is typically a childhood disease; however, adult cases carry substantially higher morbidity and mortality. Immunocompromised individuals are particularly vulnerable to severe outcomes. Many adults in Japan lack documented varicella vaccination, representing a missed opportunity for preventing primary VZV infection. None of the patients had documented prior varicella vaccination. Case Presentation: We conducted a retrospective review of varicella cases at Hirosaki University Hospital between April 2007 and March 2025. Ten patients (eight adults and two children) were identified. Among the eight adult patients, written informed consent for publication was obtained from five patients, whose clinical courses are described in detail in this report. Four patients had underlying conditions requiring immunosuppressive therapy, and two were undergoing cancer treatment. All immunocompromised patients exhibited hepatic dysfunction, with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. All patients received antiviral therapy with valaciclovir or acyclovir, and some additionally received intravenous immunoglobulin. All five adult patients in this series recovered from varicella without long-term sequelae, although one later died from unrelated causes. We additionally note that one patient later died from cerebral embolism and pneumonia, unrelated to varicella. Conclusions: This retrospective case series illustrates the vulnerability of immunocompromised adults to severe varicella and aligns with current recommendations supporting the vaccination of susceptible high-risk adults. While antiviral therapy remains essential for clinical management, prevention through appropriate vaccination strategies—varicella vaccine for preventing primary infection in eligible individuals and RZV for preventing herpes zoster reactivation in immunocompromised adults—represent an important preventive strategy for reducing overall VZV-related morbidity and mortality. These findings reinforce the importance of preventive strategies, including vaccination and early recognition of varicella in high-risk adults. Full article

This study aimed to investigate the prevalence of human pegivirus type 1 (HPgV-1) among healthy individuals, type 2 diabetes patients, and cancer patients in Taizhou, Jiangsu, China. A total of 2872 participants, including 2052 healthy individuals, 373 type 2 diabetes patients, and 447 cancer patients, were enrolled at Taizhou Fourth People’s Hospital between 2022 and 2024. Serum samples were collected from each participant, and HPgV-1 RNA was detected using a reverse transcription-polymerase chain reaction (RT-PCR) assay. The positive rates were compared across the three groups. The age range of healthy individuals was 5–91 years, while that of type 2 diabetes and cancer patients was 25–85 years and 34–91 years, respectively. The prevalence of HPgV-1 among healthy individuals was 15.3% (313/2052), which was significantly higher than that in type 2 diabetes patients (11.0%, 41/373, p < 0.05) and cancer patients (9.2%, 41/447, p < 0.001). In healthy individuals, the prevalence of HPgV-1 increased from childhood to young adulthood, peaking in the 19–40 years age group, followed by a decline after 40 years of age, indicating an age-related pattern. Similarly, HPgV-1 load increased from childhood to adulthood. No significant gender differences in HPgV-1 prevalence were observed across the three cohorts. In conclusion, HPgV-1 infection exhibits an age-dependent prevalence, with the lowest rate in children and adolescents and the highest in young adults (19–40 years). The significantly lower prevalence of HPgV-1 in type 2 diabetes and cancer patients raises the intriguing question of whether HPgV-1 infection may play a protective or contributory role in the pathogenesis of diabetes and cancers. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL) are at risk of developing long-term adverse effects after survival. This study examined observed proportions of perceived mental distress, fatigue, and executive function (EF) impairment in adult childhood cancer survivors (CCSs) of ALL, AML, and NHL. Secondly, it examined the association between perceived EF impairment and mental distress or fatigue. Participants (n = 132; 57% female) were recruited from two major Norwegian hospitals. Self-report questionnaires included the Behavior Rating Inventory of Executive Function, Adult Version, the Hopkins Symptom Checklist-25, and the Fatigue Severity Scale. Proportions exceeding established clinical thresholds were calculated, and groups were compared using Pearson’s chi-squared test and Newcombe confidence intervals. Overall, 49% and 41% of participants met the clinical thresholds for depression and anxiety; 43% for fatigue; and 28% for EF impairment. Perceived EF impairment was significantly associated with mental distress and fatigue. Mental distress, fatigue, and EF impairment are commonly reported and distressing late effects among CCSs of ALL, AML, and NHL. Follow-up care focusing on neurocognitive and psychological outcomes is important for the long-term functioning and well-being of this survivor group. Targeted neurocognitive rehabilitation may represent a key component of follow-up care. Full article

Background/Objectives: Despite overall excellent outcomes for Wilms tumour, regional variations in stage at diagnosis and care pathways remain a concern across Europe. We evaluated stage distribution, three-year survival, and treatment patterns in Italy, considering hospital care as a proxy for healthcare capacity and migration. Methods: Data were obtained from 26 population-based cancer registries (PBCRs), covering 148 patients (ages 0–14) diagnosed between 2013 and 2017, representing about 80% of the Italian population. Stage was classified according to the Toronto guidelines. Information on treatment and diagnosed/treating hospitals was collected. Stage at diagnosis was further refined using probabilistic linkage with the clinical registry 1.01 Model. Overall survival, defined as all-cause mortality, was estimated using the Kaplan–Meier method. Results: Most patients presented with localized disease (77%), 32% Stage I, while 19% were Stage IV. Three-year survival analysis showed significant differences between stages, ranging from 98% in patients with Stage I to 78% in the ones with Stage IV. No significant disparity across the Italian regions was observed in stage distribution or survival. Diagnoses and treatments were mostly (>90%) centralized in the same region for patients residing in the Centre or North of Italy. However, the cross-regional health migration from the South was of about 30% for diagnosis and larger for treatments. Conclusions: This study shows that standardized staging improves data comparability and highlights challenges in managing metastatic cases and regional care pathways. The results support the use of clinical and PBCR information to interpret survival patterns and guide improvements in paediatric oncology care. Full article

Opisthorchis viverrini (OV) is a liver fluke endemic to the Lower Mekong Basin. Infections often begin in childhood and are causally linked to cholangiocarcinoma, an often-fatal bile duct cancer. Anthelmintic treatment is the primary control strategy, but infection can recur. Therefore, additional strategies are needed. This study assessed the impact of “The Magic Glasses Opisthorchiasis” (MGO), a cartoon-based intervention, on schoolchildren’s OV-related knowledge, attitudes and practices (KAP). A cluster (school)-randomised controlled trial was conducted in Cambodia, Laos and Thailand. Clusters were randomised into either school health education only or with MGO. OV KAP was measured using a standardised questionnaire. FGDs and interviews were also conducted in intervention schools with schoolchildren, parents, and teachers. Cambodia intervention knowledge and attitude scores improved by 19.2 (p < 0.001) and 25.3 (p < 0.001) percentage points, respectively, relative to the control. Laos intervention knowledge and attitude scores improved by 19.0 (p < 0.001) and 14.2 (p < 0.001) percentage points. However, Thailand’s intervention knowledge and attitude scores declined by 23.3 (p < 0.001) and 15.8 percentage points (p < 0.001). There were no improvements in behaviour scores in any country, but parents and schoolchildren in Cambodia and Laos reported improved fish preparation practices, suggesting positive spillover effects from MGO. The findings support MGO as an effective tool for school-based health education. Full article

The incidence of cancer in young adults has risen worldwide. Women comprise a disproportionate share of young-onset cases, among whom breast cancer predominates. This shift parallels globalization and urbanization, including the wider adoption of Western-pattern diets. Although hereditary syndromes explain a minority of cases, the secular rise underscores the impact of modifiable exposures, particularly diet. Prenatal life, neonatal life, childhood, adolescence, and early adulthood are critical periods during which dietary exposures may shape long-term mammary development. Mammary tissue undergoes rapid proliferation and differentiation during development, creating windows of heightened susceptibility to carcinogenic insults. However, most existing studies emphasize dietary exposures during a single developmental period; the entire span of critical developmental windows plays a formative role in shaping young-onset breast cancer (YoBC) risk, and the mechanisms underlying this life-course shaping remain insufficiently characterized. This review comprehensively synthesizes evidence on how nutrition across sensitive developmental windows shapes the risk of YoBC. We evaluate protective and adverse dietary factors within these stages and examine mechanistic pathways linking early-life nutrition to carcinogenesis, focusing on hormonal regulation, epigenetic programming, chronic inflammation, and the gut microbiome. A structured literature search was conducted in PubMed, Embase, and Web of Science for English-language articles published from 1990 through May 2026, supplemented by hand-searching of relevant reviews and key primary studies. By framing nutrition and breast cancer through a life-course lens, this review provides an integrated foundation for stage-specific prevention strategies and identifies priority directions for future research on early-life dietary determinants of YoBC. Full article

Background: Childhood cancer survivors have a higher risk of developing malignancies later in life compared with individuals of similar age in the general population. In Spain, population-based evidence on second malignant neoplasms (SMNs) is limited. This study aimed to estimate survival following childhood cancer diagnosis and to assess the risk of SMNs in Spain. Methods: This population-based registry study used data from 12 cancer registries within the Spanish Network of Cancer Registries (REDECAN). All malignancies of sites and non-malignant central nervous system (CNS) tumors diagnosed before age 15 were included. Age-standardized incidence rates (ASIRw) for 2015–2019 were calculated. Five- and 10-year age-adjusted observed survival rates for 1990–1999 and 2000–2009 were estimated. SMN risk was assessed using standardized incidence ratios (SIRs) and excess absolute risks (EARs). Results: The ASIRw for 2015–2019 was 181.3 per million child-years. Ten-year survival increased from 71.3% in 1990–1999 to 75.5% in 2000–2009. The overall risk of developing an SMN was significantly elevated (SIR = 5.67) at 20 years. Conclusions: Although survival for childhood cancer in Spain was around 75% in 2000–2009, childhood cancer survivors remain at substantially increased risk of SMNs for at least two decades. Efforts to reduce treatment-related toxicity while maintaining survival gains are essential. Full article