• Breaking the obesity-cancer link: assessing European school-based and complementary obesity-prevention strategies and their implementation obstacles.
    3 days ago
    Nowadays, obesity among children and adolescents is considered an additional factor in cancer development during adulthood. These facts are supported by current epidemiological studies. To address these challenges, a wide range of obesity prevention programmes have been launched in Europe, promoting actions for personalized healthy dietary behaviors, physical exercise, and combinations of both, often using e-health platforms. Another pillar of interventions is school-based policies, such as limiting access to high-fat and high-sugar foods or providing healthy food vouchers, which represent another pillar of public health action, complemented by actions that cover out-of-school activities, such as family interventions, tax policies, engagement actions, and so on. However, the main limitations of the current intervention policies are their depth of penetration and, consequently, upscaling issues. Furthermore, there is a lack of a concrete approach to assess these policies within a Multi-Actor, Context-Aware framework. This multi-pillar assessment is presented in this paper for evaluating children's/adolescents' obesity programmes across fourteen European countries. The analysis includes the coverage of each programme, its financial limitations, results obtained in terms of obesity reduction and mitigation of cancer risk, along with structural and educational system limitations.
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  • Estimates of the global burden of HIV-attributable and all-cause AIDS-defining cancers: a population-based modeling study.
    3 days ago
    People living with human immunodeficiency virus (HIV; PLHIV) have elevated risks of AIDS-defining cancers (ADCs), including cervical cancer, non-Hodgkin lymphoma (NHL), and Kaposi sarcoma (KS). Previous studies have quantified the individual global burden of these cancers, we aimed to estimate the pooled global burden of HIV-attributable and all-cause ADCs in 2022 and identify the key drivers across different regions and countries.

    We conducted a systematic review and meta-analysis to update risk ratios (RRs) for cervical cancer, NHL, and KS. RRs were used to calculate population-attributable fractions (PAFs) and age-standardized incidence rates (ASIRs) of HIV-attributable ADCs using country-specific HIV prevalence and 2022 cancer incidence data. Associations with the Human Development Index (HDI) were assessed.

    In 2022, an estimated 101,835 (95% CI 76102-131,298) ADC cases were attributable to HIV, accounting for 8.1% (95% CI 6.2-10.4) of all-cause ADC cases. NHL comprised 62.9% of HIV-attributable ADCs, while cervical cancer accounted for 53.0% of all cases. The highest HIV-attributable ASIRs were in Eswatini (34.9%), Zambia (32.0%), and Mozambique (25.9%). In East and Southern Africa, 27.8% of ADCs were linked to HIV. Among 35 countries with high cancer burden and HIV attribution, 68.6% were in Africa. Lower HDI correlated with higher PAF (r = -0.27), all-cause ASIR (r = -0.25), and HIV-attributable ASIR (r = -0.28).

    HIV significantly contributes to the global ADC burden. Addressing immunosuppression, viral co-infections, and healthcare access through ART expansion, oncogenic virus monitoring, and cancer prevention is essential to mitigate the dual burden of HIV and ADCs globally.
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  • The association of the advanced lung cancer inflammation index with the risk of Helicobacter pylori infection and mortality: a study of populations from two countries.
    3 days ago
    Helicobacter pylori (H. pylori) infection is strongly linked to multiple diseases. Inflammation and nutritional status are intricately intertwined with H. pylori infection; however, most prior studies failed to integrate these two dimensions in a unified assessment.

    This study enrolled 3,718 eligible participants from the 1999-2000 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was utilized to examine the association between the ALI and H. pylori infection. Cox proportional hazards regression was employed to evaluate the association between ALI and all-cause mortality in H. pylori-infected patients. Restricted cubic splines (RCS) were implemented to characterize potential nonlinear relationships. Subgroup analysis explores the consistency of the associations among different populations. An independent duplicate cohort from the Second Affiliated Hospital of Nanchang University was additionally incorporated.

    Elevated ALI emerged as a relevant factor for H. pylori infection. Higher ALI levels were associated with improved survival prognosis. Beyond an inflection point (log2ALI=5.44) this negative association gradually diminished. Subgroup analyses revealed that the interaction test showed that no significant interaction was found for all stratification factors. The association between ALI and H. pylori infection was consistent among the above subgroups. Independent duplicate cohort corroborated that as the level of log2ALI increases, the likelihood of H. pylori infection showed a monotonous increasing trend.

    Higher ALI levels were positively associated with an increased risk of H. pylori infection, and this association was consistent in an independent duplicate cohort. Among H. pylori-infected individuals, higher ALI was related to reduced all-cause mortality, with the association most prominent at lower ALI ranges.
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  • Comparison of live birth rates between calorie-restricted diet and metformin prior to ovulation induction therapy in women with polycystic ovary syndrome and overweight/obesity: a protocol for a multicenter, randomized comparative effectiveness trial.
    3 days ago
    Polycystic ovary syndrome (PCOS) significantly impairs physical and mental health, quality of life, and fertility in women of reproductive age. Strategies to enhance fertility in PCOS have been prioritised in International Guidelines. Whilst Guidelines recommend Letrozole in first line ovulation induction (OI), therapeutic interventions to optimise endocrine and metabolic PCOS features prior to OI have not been adequately researched despite potential to improve live birth and pregnancy outcomes. Whilst both a calorie-restricted (CR) diet and metformin interventions may offer benefits in the context, evidence is limited including for live birth rates, and pregnancy outcomes. Therefore, this study will aim aims to compare the effects of a CR diet versus metformin on live birth, endocrine, reproductive, and metabolic parameters as well as pregnancy outcomes in women with PCOS and overweight/obesity.

    This multicenter, randomized (1:1) comparative effectiveness trial will evaluate and compare the effects of a CR diet versus metformin, administered for 12 weeks prior to OI, on live birth, endocrine, metabolic, reproductive, and pregnancy outcomes in women with PCOS and overweight/obesity. The primary analysis will follow the intention-to-treat principle, including all participants who underwent randomization.

    This trial investigates the comparative efficacy of a CR diet versus metformin over a 12-week period prior to OI therapy in women with PCOS and overweight/obesity. Early therapeutic intervention holds significant potential to disrupt the pathophysiological cycle characterized by hyperandrogenism, excessive adiposity, and insulin resistance for improving fertility and pregnancy outcomes.

    ClinicalTrials.gov, identifier NCT06049186.
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  • Dynamic serum tumor-marker and immune-inflammatory biomarker changes for risk stratification of immune checkpoint inhibitor-associated myasthenia gravis in non-small cell lung cancer.
    3 days ago
    Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of non-small cell lung cancer (NSCLC), but immune-related neuromuscular toxicities remain difficult to anticipate. ICI-associated myasthenia gravis is uncommon, frequently occurs early after treatment initiation, and may overlap with myositis or myocarditis. Clinically accessible blood-based indicators that help identify patients entering this high-risk period remain insufficiently defined.

    This study evaluated whether early dynamic changes in serum tumor markers and immune-inflammatory biomarkers could serve as noninvasive indicators of subsequent ICI-associated myasthenia gravis in patients with NSCLC.

    Consecutive patients with NSCLC who received their first ICI-based therapy between 1 January 2018 and 31 January 2025 were retrospectively screened at a single center. Baseline, Day-21, and Day-42 laboratory windows were prespecified before endpoint modeling. Serum tumor markers included carcinoembryonic antigen, cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, squamous cell carcinoma antigen, and carbohydrate antigen 125. Immune-inflammatory biomarkers included neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, C-reactive protein, lactate dehydrogenase, and albumin. The primary endpoint was definite or probable ICI-associated myasthenia gravis occurring within 180 days after first ICI exposure. Landmark models were developed using Firth bias-reduced logistic regression and internally validated by bootstrap resampling. The Day-21 dynamic score used clinically pragmatic thresholds defined before endpoint modeling.

    The final baseline cohort included 826 patients, of whom 27 developed definite or probable ICI-associated myasthenia gravis within 180 days. The Day-21 landmark cohort included 782 patients and 21 events occurring after Day 21. Compared with non-event patients, patients who later developed ICI-associated myasthenia gravis showed greater Day-21 increases in cytokeratin 19 fragment antigen 21-1, carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, C-reactive protein, and lactate dehydrogenase, together with a larger decline in albumin. A four-component Day-21 dynamic score combining tumor-marker instability, neutrophil-to-lymphocyte ratio activation, C-reactive protein/lactate dehydrogenase flare, and albumin decline stratified event rates after Day 21 from 1.2% in the low-risk group to 6.7% in the high-risk group. The integrated Day-21 model achieved an apparent area under the receiver operating characteristic curve of 0.759 and an optimism-corrected area under the receiver operating characteristic curve of 0.731, indicating moderate internal discrimination.

    Early dynamic changes in routine serum tumor markers and immune-inflammatory biomarkers were associated with increased risk of ICI-associated myasthenia gravis in patients with NSCLC. The Day-21 integrated biomarker score may help identify patients requiring closer neuromuscular and cardiac toxicity surveillance during the first few weeks of ICI therapy, but external validation is required before clinical implementation.
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  • Diagnostic value of endothelial-specific molecule-1 levels in patients with bone tumors.
    3 days ago
    In suspected bone tumors where imaging and histopathological evaluation are fundamental for diagnosis, minimally invasive blood biomarkers are needed for earlier diagnosis, initial assessment, and risk stratification. The aim of this research was to evaluate the diagnostic value of Endothelial-Specific Molecule-1 (ESM-1) levels in determining the presence of bone tumors and distinguishing between benign and malignant tumors.

    This cross-sectional research, conducted at a research hospital, involved 60 participants diagnosed with bone tumors and 30 healthy participants. ESM-1 values were analyzed using Enzyme-Linked Immunosorbent Assay (ELISA). The data obtained were evaluated using binary logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis.

    ESM-1 values were determined to be higher in the bone tumors group than in the control group. ROC analysis showed an Area Under the Curve (AUC) of 0.895. Using a cut-off value of 138.94 ng/L for detecting bone tumors, the sensitivity and specificity were 78.3% and 80.0%, respectively. In addition, ESM-1, erythrocyte sedimentation rate, and C-reactive protein levels were found to be higher in the malignant subgroup than in the benign subgroup. In subgroup ROC analysis, ESM-1 perfectly discriminated against malignant tumors from both benign tumors (AUC = 1.000) and healthy controls (AUC = 1.000), with sensitivities and specificities of 100% at cut-off values of 204.54 ng/L and 195.00 ng/L, respectively. For differentiating benign tumors from healthy controls, the AUC was 0.789, with 70.0% sensitivity and 70.0% specificity at a cut-off value of 125.54 ng/L.

    ESM-1 levels may have potential diagnostic value in distinguishing between bone tumors and malignant tumors; however, these results need to be confirmed in larger samples.
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  • Oral microbiota and serum metabolomics features in newly diagnosed anti-AchR antibody-positive myasthenia gravis patients.
    3 days ago
    Myasthenia gravis (MG) is an autoimmune disorder mediated by autoantibodies. While research regarding the microbiota-gut-brain axis has expanded significantly in recent years, the role of the oral microbiota in MG and its potential association with systemic metabolism remain poorly understood. To address this, we conducted a case-control study to investigate potential alterations in the oral microbiota and serum metabolites in newly diagnosed and treatment-naïve patients with MG.

    In total, 38 newly diagnosed and treatment-naïve anti-AchR antibody-positive MG patients were recruited, including 19 with ocular myasthenia gravis (OMG) and 19 with generalized myasthenia gravis (GMG), along with 29 healthy controls (HCs). Saliva and serum samples were collected for 16S rRNA gene high-throughput sequencing and untargeted metabolomic profiling, respectively. Data processing and integration were performed using multiple bioinformatics and statistical methods, including α- and β-diversity analyses, LEfSe, Spearman correlation, and metabolic pathway enrichment analysis.

    Compared with HCs, patients with OMG and GMG exhibited significant dysbiosis. At the phylum level, the abundance of Bacillota was significantly increased, whereas that of Bacteroidota and Campylobacterota was significantly decreased. At the genus level, the abundances of Streptococcus and Bifidobacterium were significantly elevated; in contrast, those of Prevotella and others were significantly reduced. Serum metabolomics analysis identified distinct metabolic disorders in MG patients, involving key pathways such as lipid metabolism, neuroactive ligand-receptor interaction, and amino acid metabolism. Correlation network analysis further revealed significant associations between specific oral genera (Streptococcus, Bifidobacterium) and differential metabolites primarily involved in lipid metabolism, amino acid metabolism, and terpenoid and polyketide metabolism in both OMG and GMG populations.

    In MG patients, significant oral dysbiosis may be associated with MG-related metabolic alterations by disrupting metabolic pathways, such as those associated with lipid and amino acid metabolism.
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  • Prognostic value of glycemic variability for ICU and in-hospital all-cause mortality in postoperative patients with upper gastrointestinal cancer: a retrospective cohort study.
    3 days ago
    Most studies on upper gastrointestinal cancer (UGIC) only focus on static glycemic markers while neglecting glycemic variability (GV). The prognostic role of GV and its subgroup heterogeneity, especially across coronary artery disease (CAD) status, remain unclear. This study aimed to explore the independent predictive value, non-linear pattern and clinical heterogeneity of GV for Intensive Care Unit (ICU) and in-hospital mortality in UGIC postoperative patients.

    This study retrospectively collected and analyzed clinical data from postoperative patients with UGIC at Quzhou People's Hospital. Survival analyses were employed. They were Kaplan-Meier curves, Cox proportional hazards models, and restricted cubic splines. The study outcomes were 56-day ICU and in-hospital mortality. Subgroup analyses were performed, and three tree-based machine-learning prediction models were implemented, including the random-forest model via the ranger package (version 0.16.0), the XGBoost gradient-boosting model via the XGBoost package (version 1.7.5), and the LightGBM model. Model performance was evaluated and we employed the area under the receiver operating characteristic curve, along with the SHapley Additive exPlanations package, to interpret feature contributions.

    Elevated GV independently predicted higher ICU and in-hospital mortality, with spline curves suggesting a potential non-linear-like trend, although formal statistical tests did not confirm a statistically significant nonlinear association. GV and SOFA score were the top prognostic predictors. The GV-mortality association differed between two endpoints and presented obvious CAD-related subgroup heterogeneity. In-hospital mortality better reflected the full prognostic impact of GV, especially in mechanically ventilated and CAD-free patients.

    GV is a standalone predictor for ICU and in-hospital all-cause mortality in patients with UGIC, exhibiting a non-linear-like trend and demonstrating robustness across diverse patient populations. Maintaining GV may represent a valuable clinical strategy for improving outcomes in this patient population.
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  • Systematic adolescent-centered supportive care program is associated with improved psychological status, treatment adherence, and social adaptation in adolescents with thyroid cancer undergoing radioiodine-131 therapy: a retrospective before-after cohort study with historical controls.
    3 days ago
    Adolescents and young adults (AYAs) with differentiated thyroid cancer (DTC) undergoing radioiodine-131 (131I) therapy endure unique developmental and psychosocial challenges, yet evidence for adolescent-tailored supportive interventions remains scarce. This retrospective before-after cohort program is associated with improvements in psychological distress, treatment adherence, and social reintegration.

    We enrolled 220 eligible patients aged 13-25 years with DTC receiving131I therapy (2016-2024). The control group (n=85) received routine care, while the observation group (n=135) received a multi-component supportive care program. It included narrative medicine interviews, radiation education, fertility and career counseling, social adaptation training, and sustained follow-up. Primary outcomes were anxiety (SAS) and depression (SDS) scores. Secondary outcomes covered adherence, social adaptation, fertility cognition and satisfaction. Linear mixed-effects models analyzed repeated SAS/SDS data; propensity score inverse probability weighting(IPTW), multivariable regression and Benjamini-Hochberg FDR correction were applied to adjust confounders and handle multiple comparisons.

    In linear mixed-effects models, the observation group exhibited significantly lower 6-month SAS and SDS scores (all adjusted P < 0.001).Significant group×time interactions for both scales demonstrated sustained psychological improvements. In multivariable logistic regression analyses adjusting for potential confounders, the observation group also achieved superior treatment adherence( aOR = 2.71   , 95 %CI : ( 1.52 - 4.83 ) , school/work resumption rates ( aOR = 2.35 , 95 % CI : 1.22 - 4.51 ) , and medical satisfaction ( aOR = 2.01 , 95 % CI : 1.11 - 3.64 ) ( allFDR - P < 0.05 ) .IPTW sensitivity analyses corroborated these findings. Exploratory subgroup analyses did not reveal consistent evidence of differential intervention effects across most subgroups.

    A standardized adolescent-centered supportive care program was associated with persistent anxiety and depression relief, improved adherence and social reintegration among AYAs with DTC receiving 131I therapy. While these real-world findings support program feasibility, prospective multicenter randomized trials are required to confirm causal efficacy.
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  • Retrospective Single Center Assessment of Routes to Penile Cancer Diagnosis and the Role of Penile Biopsy.
    3 days ago
    To examine the routes to penile cancer diagnosis and the role of penile biopsy.

    This retrospective observational study from a tertiary referral center included 625 patients referred as urgent suspected penile cancer within the Danish Cancer Patient Pathway (CPP) and 216 patients undergoing penile biopsy outside the CPP between January 1, 2021 and March 31, 2025. The main outcomes were the number of patients diagnosed within and outside the CPP and secondary outcomes included biopsy findings, the ratio between urgent suspected penile cancer referrals and the number of patients subsequently diagnosed with penile cancer.

    Among 529 patients referred under the CPP for suspected penile cancer, only 10% were diagnosed with cancer. Biopsy confirmed cancer was more frequent within the CPP, though overall cancer detection rates were similar (~10%). Patients biopsied outside the CPP were younger and more often had prior biopsies. Complication rates after penile biopsy were low and comparable between groups. Diagnostic concordance between clinical suspicion and histology was slight (κ = 0.20, SE 0.04) for cancer and fair (κ = 0.33, SE 0.05) for PeIN. Biopsies demonstrated both diagnostic and therapeutic value, occasionally altering clinical management.

    The CPP identifies a higher proportion of malignancies but with a low overall conversion ratio, and some cancers are still diagnosed outside the pathway. Penile biopsy is safe and essential for accurate diagnosis due to low clinical-histological concordance, with added therapeutic value. Continued focused penile biopsy use, including re-biopsy in uncertain cases, is warranted to ensure optimal management and oncological safety.
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