An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.
Background: In the Lombardy Region, Italy, HPV vaccination is recommended and offered free of charge to 12-years-old males since 2017. The expected vaccination thresholds are still far to be reached. Methods: A cross-sectional survey to investigate parents’ attitudes towards the HPV vaccine and knowledge about HPV was administered to parents of boys aged 6 to 18 years attending a large pediatric hospital for outpatient specialistic evaluations. Two parallel multiple logistic regression analyses were conducted to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for attitude towards HPV vaccination and perceived need for more information about HPV vaccination. Results: A positive attitude towards HPV vaccination was found in 74% of interviewed parents. Knowledge of HPV, having a generally positive attitude toward vaccination, and mothers filling in the survey were positively associated with a positive attitude to the HPV vaccine. Parents’ perceived need for more information about HPV vaccination was positively associated with the child’s age, general positive attitude toward vaccination, Christian religion, and positive attitude toward HPV vaccination; knowing that HPV vaccination is free of charge significantly reduced the risk of asking for more information on HPV vaccination. Conclusions: The majority of parents of male children and adolescents in our study have a positive attitude toward HPV vaccination. Attitude toward HPV vaccination and perceived need for more information on HPV vaccination were directly related to a positive attitude toward vaccines in general. In addition, knowledge of HPV and related pathologies favors a positive attitude toward HPV vaccination. Future health programs should target an even wider diffusion of evidence-based information on vaccines in general and on the HPV vaccine in young males, to support a positive attitude toward vaccines in the general population.
Background/Objectives: Prevalence and burden of chronic obstructive pulmonary disease (COPD) are projected to increase in the coming decades. Although prognostic models for disease progression and exacerbation risk have proliferated, especially with the advent of machine learning (ML), their methodological rigor, generalizability, and predictive performance remain inconsistent. This study aimed to systematically review prognostic models for disease progression in adults with COPD, including traditional regression-based methods and ML techniques, evaluating model performance, sources of heterogeneity and methodological issues. Methods: PubMed and Embase were searched for all studies that developed and/or validated prognostic models for mortality (overall and cause-specific), exacerbations, or hospitalizations in adults with COPD over a time window of 1–5 years. Methodological quality was appraised using PROBAST. Model performance was summarized descriptively, and discrimination (c-statistic) was meta-analyzed for externally validated models with sufficient homogeneity. Results: Eighty-seven studies presenting 193 prognostic models across 96 unique cohorts were included. Only 7% of models were based on ML. Thirty-eight percent of records were validations of multidimensional indices. All-cause mortality (n = 85), severe exacerbations (n = 38) and moderate/severe exacerbations (n = 16) were the most frequently studied outcomes. Meta-analysis of exacerbation models was hampered by insufficient homogeneity (median c 0.74). As for mortality, BODE outperformed other indices (pooled c 0.75). Over 40% of studies were flawed by a high risk of bias. Conclusions: Despite a comprehensive literature search and thorough data extraction, we were able to provide a meaningful quantitative synthesis only for externally validated mortality models, as pooling results for other individual outcomes was precluded by substantial heterogeneity. Our findings highlight the predominance of regression approaches, the limited use of ML, the presence of persistent methodological limitations and the need for more robust, validated models capable of handling complex, multimodal patient data.
The aim of this study is to evaluate if the alignment with the 2020-2025 Dietary Guidelines for Americans (DGA), measured by the Healthy Eating Index 2020 (HEI-2020), is associated with colorectal cancer (CRC) risk in an Italian population. A multicentric case-control study was carried out in Italy between 1992 and 1996. Cases were 1953 patients (males 58 %, median age = 62 years) admitted to major hospitals with incident, histologically confirmed CRC. Controls were 4154 patients (males 50 %, median age = 58 years) admitted to the same hospitals for acute non-neoplastic conditions. Participants' usual diet before study enrolment was collected using a validated food frequency questionnaire, and the alignment with DGA was assessed using the HEI-2020 score, ranging between 0 (no alignment) and 100 (complete alignment). Odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were estimated using multiple logistic regression models including terms for selected socioeconomic, lifestyle factors, and potential confounders. The HEI-2020 score ranged from 29.4 and 97.0. Subjects in the highest tertile of scores had lower risk of CRC compared to those in the lowest tertile (OR: 0.69, 95 % CI = 0.60-0.80). Similar estimates were found for colon (OR: 0.70, 95 % CI = 0.59 - 0.83) and rectal cancer (OR: 0.69, 95 % CI = 0.56-0.85). The findings were also consistent across strata of different covariates. Alignment with DGA was inversely associated with CRC risk in an Italian population.