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Background: Lung cancer screening (LCS) combined with smoking cessation programs is a critical strategy for reducing lung cancer mortality. Understanding the perspectives of cigarette users and former ones on these interventions is essential for enhancing their acceptability and effectiveness. This study aimed to explore, in Italy, the perceptions and experiences of individuals eligible for LCS within the context of a smoking cessation program., Methods and Findings: This multicenter qualitative study was conducted in two Italian regions as part of a larger project the Italian League against Cancer promoted. Using purposive sampling, we included (a) cigarette users and former ones who participated in an Italian trial, ITALUNG study, and (b) cigarette users who had been offered individual or group smoking cessation interventions and were theoretically eligible for screening in the following years (aged 50-70, ≥15 pack-years). Data were collected through open-ended semi-structured interviews and focus group meetings and analyzed using reflexive thematic analysis. The data analysis yielded six themes covering participants' views on the interactions between the two types of interventions (screening and smoking cessation program). Across their data, we generated the following themes: (i) depreciation and fatalism toward the risk of smoking, (ii) self-blaming and ethicality, (iii) ambivalent impact of the screening on smoking, (iv) LCS-related information and concerns, (v) teachable and motivating moments, and (vi) non-stigmatizing communication and testimony by professionals., Conclusions: Our study underscores the importance of avoiding stigma and respecting the dignity of cigarette users in implementing LCS and smoking cessation programs. Clear communication and supportive interactions with healthcare providers are crucial for enhancing the acceptability and effectiveness of these interventions. Future research should focus on quantifying these findings and exploring additional factors influencing the acceptability and effectiveness of combined LCS and smoking cessation programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ghirotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR 1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa., Methods: Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient., Results: When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships., Conclusions: miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Association between dietary factors and the risk of developing inflammatory bowel disease (IBD) has been studied extensively. However, identification of deleterious dietary patterns merits further study., Aim: To investigate the risk of developing Crohn's disease (CD) and ulcerative colitis (UC) according to the inflammatory score of the diet (ISD) in the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: We used validated food frequency questionnaires collected at baseline to compute ISD scores. We estimated the association between ISD score and risks of CD and UC risks using Cox models stratified by centre, sex and age. We adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake., Results: We included 394,255 individuals including 184 incident cases of CD and 459 of UC after median follow-up of 13.6 years (4,889,910 person-years). High ISD scores were associated with a higher risk of CD (fourth vs. first quartile-adjusted HR: 1.88, 95% CI: 1.14-3.10; p-trend < 0.01) but not of UC (adjusted HR: 0.85, 95% CI: 0.63-1.15; p-trend 0.21). For CD, this association was mainly observed for women (adjusted HR: 2.14, 95% CI: 1.17-3.91; p-trend < 0.01). On subgroup analyses, those differences were mainly driven by low intakes of fibre, mono-unsaturated fatty acids, vitamin C, magnesium, onion and alcohol., Conclusions: A high ISD score is associated with a higher risk of developing CD but not UC. These results should be taken into account in high-risk populations., (© 2025 John Wiley & Sons Ltd.)

Outdoor air pollution is a significant risk factor for tracheal, bronchus, and lung (TBL) cancer. This study employs a Bayesian approach to evaluate TBL cancer mortality due to air pollution in Tuscany, Central Italy, in 2023. Using locally validated data, we assessed the impact of fine particulate matter (PM 10 and PM 2.5 ) and nitrogen dioxide (NO 2 ) in terms of attributable deaths and years of life lost (YLL). Our three-step methodology included: (1) Bayesian modeling to derive posterior distributions for life expectancy, pollution levels, mortality rates, and exposure-response functions (inputs); (2) Monte Carlo simulations to propagate uncertainty from the inputs to the impact metrics (outputs); and (3) Global Sensitivity Analysis (GSA) to quantify the influence of each input on the outputs. The largest impact was estimated for PM 2.5 , with 432 deaths (50% CrI: 174;705) and 6,500 YLL (50% CrI: 2,624;10,613) in the region due to annual average concentrations exceeding the WHO threshold of 5μg/m 3 . Central districts, with higher exposure levels, were particularly affected, reporting 14 attributable deaths and 207 attributable YLL per 100,000 inhabitants. The GSA indicated that uncertainty in exposure-response functions and annual average concentrations of air pollutants significantly affected outcomes, highlighting the need to strengthen the regional air quality network and conduct local studies to address effects heterogeneity. Our findings highlight the value of high-quality local health assessments for identifying critical areas, setting intervention priorities, and informing context-specific action plans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Aims: Dicarbonyl compounds such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) are present in numerous foods. They are pro-inflammatory and pro-oxidative, but their potential role in cardiovascular disease (CVD) development has been scarcely studied. We explored associations between dietary dicarbonyls with fatal and non-fatal CVD., Methods and Results: We conducted a case-cohort analysis based on 32 873 subjects drawn from 346 055 participants of the multi-national prospective EPIC cohort. Cases (15 863 subjects) were CVD-free at baseline and later developed CVD [coronary heart disease (CHD) and/or stroke] with non-fatal (n CVD = 17 837; n CHD = 12 003; n stroke = 6791; not mutually exclusive) and/or fatal (n CVD = 2894; n CHD = 2284; n stroke = 908) outcomes. Dietary intake of dicarbonyl compounds was estimated using country-specific questionnaires linked to a food composition database of dicarbonyl compounds. Multivariable prentice weighted Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident non-fatal and fatal CVD. The main food sources of dicarbonyl compounds include cereals, sugar and confectionaries, coffee, fruits, and vegetables. Higher dietary dicarbonyl intakes were inversely associated with non-fatal CVD (per 1 SD increase, GO: HR = 0.95, 95% CI 0.92-0.98; 3-DG: HR = 0.95, 95% CI 0.92-0.98), fatal CVD (MGO: HR = 0.92, 95% CI 0.87-0.97; GO: HR = 0.91, 0.86-0.96; 3-DG: HR = 0.93, 0.86-0.99), non-fatal CHD (3-DG: HR = 0.95, 0.92-0.99), non-fatal stroke (MGO: HR = 0.93, 95% CI 0.90-0.96; GO: HR = 0.90, 95% CI 0.86-0.95; 3-DG: HR = 0.92, 95% CI 0.89-0.96), and fatal CHD (MGO: HR = 0.94, 95% CI 0.88-0.99; GO: HR = 0.92, 0.86-0.98; 3-DG: HR = 0.89, 0.82-0.96)., Conclusion: Higher intakes of dietary MGO, GO, and 3-DG intake are associated with lower risk of non-fatal or fatal CVD. Further research is required to confirm these findings, assess circulating levels of dicarbonyls, and explore potential underlying mechanisms for their observed CVD risk associations., Lay Summary: Dicarbonyl compounds are known to promote oxidative stress, inflammation, endothelial dysfunction, and vascular complications. They are formed endogenously in the body as a byproduct in glucose metabolism but are also present in some foods during food preparation and processing. We studied the role of three major dicarbonyl compounds coming from foods on cardiovascular diseases using data from the prospective EPIC cohort, which includes over 520 000 participants from 10 European countries.We observed that higher consumption of dietary dicarbonyl compounds resulted in a lower risk of non-fatal or fatal CVD.Our findings highlight the need to better understand the roles of these dietary compounds along with their potential underlying mechanisms of action., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: Associations of saturated and unsaturated fatty acids (FAs) with cardiovascular disease (CVD) remain controversial. We therefore aimed to investigate the prospective associations of objectively measured FAs with CVD, including incident coronary heart disease (CHD) and stroke, as well as CVD mortality., Methods and Results: Circulating FA concentrations expressed as the percentage of total FAs were assayed in 172 891 participants without prior vascular disease at baseline from the European Prospective Investigation into Cancer and Nutrition-CVD (EPIC-CVD) (7343 CHD; 6499 stroke), UK Biobank (1825; 1474), and INTERVAL (285; 209) cohort studies. Hazard ratio (HR) per 1-standard deviation (SD) higher FA concentrations was estimated using Cox regression models and pooled by random-effects meta-analysis. Systematic reviews with meta-analysis published by 6 May 2023 on associations between FAs and CVDs were systematically searched and updated meta-analyses using random-effects model were conducted. Evidence from randomized controlled trials (RCTs) was also summarized. Higher concentrations of total saturated FAs (SFAs) were associated with higher cardiovascular risks in the combined analysis, with differential findings noted for SFA sub-types in further analysis restricted to EPIC-CVD: positive associations for even-chain SFA [HR for CHD 1.24 (95% CI: 1.18-1.32); stroke 1.23 (1.10-1.38)] and negative associations for odd-chain [0.82 (0.76-0.87); 0.73 (0.67-0.78)] and longer-chain [0.95 (0.80-1.12); 0.84 (0.72-0.99)] SFA. In the combined analysis, total n-3 polyunsaturated FA (PUFA) [0.91 (0.85-0.97)], including docosahexaenoic acid (DHA) [0.91 (0.84-0.98)], was negatively associated with incident CHD risk. Similarly, total n-6 PUFA [0.94 (0.91-0.98)], including linoleic acid (LA) [0.89 (0.83-0.95)], was negatively associated with incident stroke risk. In contrast, more detailed analyses in EPIC-CVD revealed that several downstream n-6 PUFAs of LA were positively associated with CHD risk. Updated meta-analyses of 37 FAs including 49 non-overlapping studies, involving between 7787 and 22 802 CHD cases and between 6499 and 14 221 stroke cases, showed broadly similar results as our combined empirical analysis and further suggested significant inverse associations of individual long-chain n-3 PUFAs and LA on both CHD and stroke. The findings of long-chain n-3 PUFAs were consistent with those from published RCTs on CHD despite insufficient evidence in monotherapy, while RCT evidence remained unclear for the rest of the explored FAs., Conclusion: Our study provides an overview of the most recent evidence on the associations between objectively measured FAs and CVD outcomes. Collectively, the data reveal notable differences in associations by SFA sub-types and call for further studies, especially RCTs, to explore these links., Competing Interests: Conflict of interest: E.S. and L.S. contributed to this work while employed full-time by the University of Cambridge, but are currently employed full-time by AstraZeneca PLC (E.S.) and Regeneron Genetics Center LLC (L.S.). T.Y.N.T. for grant support from Medical Research Council (MR/M012190/1) and UK Research and Innovation (MR/X032809/1); N.F. for reimbursement of travel expenses for meetings of the EAT-Lancet Commission on food, health and planetary sustainability; J.D. for grants outside of present manuscript from Astra Zeneca, Merck Sharp & Dohme Corporation and Novartis; and A.S.B. for grants outside of this work from AstraZeneca, Bayer, BioMarin, Regeneron and Sanofi. J.D. stated other relationships, interests, or activities, including Cambridge University Hospital NHS Foundation Trust (Honorary Consultant), UK Biobank (Steering Committee), MRC International Advisory Group (Member), MRC High Throughput Science ‘Omics Panel (Member), Scientific Advisory Committee for Sanofi (Member), Wellcome Sanger Institute (Faculty Member) and Novartis (Advisor)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach., Methods: Analyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (more than 20 000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the association., Results: MR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits., Conclusion: The results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The association between socioeconomic position (SEP) and non-communicable diseases (NCDs) is well established, but its role in driving multimorbidity remains unclear. Multimorbidity, defined as the co-occurrence of more than one chronic condition, is linked to higher mortality and reduced quality of life. This study investigates the association between SEP and multimorbidity using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Incident cases of cancer, type 2 diabetes (T2D), and cardiovascular diseases (CVDs) were analysed alongside lifestyle factors such as smoking status, alcohol intake, body mass index (BMI), physical activity and diet. Multimorbidity was defined as the presence of at least two of the studied NCDs. SEP was assessed using the Relative Index of Inequality (RII) and categorized into high, medium, and low SEP. The cohort included 277 302 participants (60.7% women) from seven countries, enrolled between 1992-2000 and followed until the first diagnosis, end of follow-up (31/12/2007), or death. For transitions to multimorbidity, follow-up extended from the first diagnosis to the second diagnosis, end of follow-up, or death. Multistate models were used to examine the nine possible transitions to first diagnoses and multimorbidity combinations. Lifestyle factors were risk factors for all the transitions, except alcohol intake. In the main model, not stratified by sex, low SEP was associated with higher risks of progressing from cancer to CVD (Hazard Ratio (HR): 1.23, CI: 1.02-1.50), CVD to T2D (HR: 1.35, CI: 1.07-1.71), and cancer to T2D (HR: 1.37, CI: 1.10-1.69). These findings highlight the persistent influence of social inequalities on the risk of multimorbidity, even in individuals with an existing chronic condition.

Industrial food processing has been linked to various health outcomes including cancer. To examine associations between the degree of food processing and risk of colorectal cancer (CRC) and its sub-sites, data from the European Prospective Investigation into Cancer (EPIC) including 6155 incident CRC cases (n = 450,111 participants), were analyzed. Dietary intakes were assessed using baseline food frequency questionnaires. Foods were classified into culinary ingredients, unprocessed, processed (PFs), and ultra-processed foods (UPFs) according to the Nova classification. Cox proportional hazards models, adjusted for established CRC risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with a 10% increase in proportion of consumption (%g/d) of each Nova group. Substitution analysis examined the effect of replacing UPFs and PFs with unprocessed foods on CRC risk. A 10% increase in proportion of UPFs was associated with 6% higher CRC risk (95% CI:1.02-1.10). A positive association was also found between PFs and CRC risk (HR per 10% increase: 1.10 [95% CI, 1.05-1.15]). Conversely, unprocessed food consumption was inversely associated with CRC risk (HR per 10% increase: 0.93[95% CI, 0.90-0.95]). Substitution of 10% of the overall proportion of the diet comprising UPFs or PFs with 10% unprocessed foods was associated with a decreased risk of CRC (HR UPFs : 0.94 [95% CI, 0.90-0.97]; HR PFs : 0.90 [95% CI, 0.86-0.94]). In conclusion, UPF was positively associated with CRC risk while diets richer in unprocessed foods were associated with lower CRC risk. Further studies are needed to understand the mechanisms by which food processing affects CRC risk., (© 2025 UICC.)

Background: The lockdowns imposed by the government during coronavirus disease 2019 (COVID-19) pandemic have had a significant impact on the Italian population habits., Methods: LOckdown and lifeSTyles in Italy and in Tuscany studies collected data on a representative sample of the Italian adult population in 2020 (n = 6,003) followed up through 2023 via four additional surveys (3,000 ≤ n ≤ 6,600) through an online self-administered questionnaire. The Alcohol Use Disorders Identification Test-Concise was used to identify at-risk drinkers. Considering the cohort of individuals who took part to the first and at least one other wave (n = 5,378), a multilevel logistic model was used to derive odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of being at-risk drinkers., Results: The prevalence of at-risk drinkers was 26.4% before, 23.4% during the first lockdown, and stabilized around 30.0% thereafter. Being at-risk alcohol consumers decreased with decreasing economic status (P for trend <0.001), was less frequent among middle-aged compared to younger (OR 0.73; 95% CI, 0.60-0.89) and among divorced/separated (OR 0.77; 95% CI, 0.60-0.99) or single (OR 0.75; 95% CI, 0.64-0.89) compared to married individuals. It was more frequent among individuals with anxiety or depressive symptoms (OR 1.24; 95% CI, 1.12-1.37), those using psychotropic drugs (OR 1.99; 95% CI, 1.69-2.35) and users of conventional and/or alternative nicotine products (OR 3.67; 95% CI, 3.00-4.48)., Conclusion: The long-term trends in alcohol consumption after the COVID-19 pandemic are unfavorable in Italy. The results point to an increased vulnerability for at-risk alcohol consumption among younger individuals, women with higher economic status, and married individuals. At-risk drinking is strongly related to mental health symptoms and nicotine consumption.

Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear., Methods: Targeted metabolomics data from 6,055 participants in the EPIC cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-CRC association., Results: PA was inversely associated with CRC risk (odds ratio [OR] per category change: 0.90, 95% confidence intervals [CI]: 0.83, 0.97; p-value = 0.009). PA levels were associated with 24 circulating metabolites after false discovery rate correction (FDR), with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated the PA-CRC association (natural indirect effect: 0.991, 95% CI: 0.982, 0.999; p-value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature., Conclusions: PC ae C34:3 mediates part of the PA-CRC inverse association, but further studies with improved PA measures and extended metabolomic panels are needed., Impact: These findings provide insights into PA-related biological mechanisms influencing CRC risk and suggest potential targets for cancer prevention interventions.

Background: The aim of the study is to evaluate the incidence of recurrence of acquired cholesteatoma and functional outcomes in patients who underwent CWD tympanoplasty with cavity obliteration using an inferior-based musculoperiosteal flap. A comparison between children and adults was conducted. Methods: All surgeries performed by the same expert surgeon from 2016 to 2019 were considered for the study. Patients younger than 18 years old, operated on at Meyer's Children Hospital, formed group A. Patients older than eighteen, operated on at Santo Stefano Hospital, formed group B. Clinical, audiological, and radiological data were collected from medical records. The Air Bone Gap (ABG) was used to assess the audiological results, and outpatient evaluations were considered to detect cases of recurrence. Results: Group A and Group B are composed of 23 and 25 patients, respectively. The postoperative ABG is 30.7 dBHL in group A and 29.5 dBHL in group B. The rate of recurrence is 17.2% in children and 8% in adults. The recurrence of cholesteatoma occurred in five children (21.8%) after an average follow-up of 18 months and in three adults (12%) after an average follow-up of 24 months. Conclusion: The surgical approach to CCOM in children aims to be as conservative as possible. The greater extension of the pathology is correlated with a greater erosion of the ossicular chain. According to our experience, open tympanoplasty with the obliterative technique allows us to obtain good anatomical and audiological outcomes, both in adults and children.

BackgroundTobacco use is linked to increased cancer risk, and people who smoke represent a large proportion of newly diagnosed patients with cancer. The fact that smoking cessation at the time of diagnosis can improve the patient's life expectancy is still not broadly understood. We conducted a systematic review and meta-analysis to quantify the survival benefits obtainable by quitting smoking on diagnosis.We included articles found in MEDLINE and EMBASE until 2 January 2024. We conducted a random effects meta-analysis, studying correlates of between-studies heterogeneity and exploring the presence of publication bias.There were 36 eligible studies published in 1980-2023, totalling over 17 000 actively smoking patients with cancer. The most studied cancer sites were the lung (n=17) and head and neck (n=14). The median proportion of patients who quit on diagnosis was 42.5%. Postdiagnosis cessation was associated with longer overall survival (summary HR (sHR) 0.71, 95% CI 0.65 to 0.78), progression-free survival (sHR 0.64, 95% CI 0.41 to 0.98), disease-free/recurrence-free survival (sHR 0.59, 95% CI 0.43 to 0.81) and improved local/locoregional control (sHR 0.69, 95% CI 0.50 to 0.94). Heterogeneity was generally large; for overall survival, study results were stronger when properly adjusted but did not vary across cancer sites. There was evidence for publication bias, but the results were only marginally altered on imputation of potentially missing studies.Postdiagnosis smoking cessation is effective in improving the chances of survival for patients with cancer. Cessation support programmes should be integrated into the routine management of patients with cancer as they may favourably affect survival., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population., Methods: This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions. Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding. The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here). This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment. The safety population comprised patients who received the study intervention at least once after randomisation. The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting., Findings: Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n=365) or endocrine therapy (n=366). This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2). Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group. 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment. The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group. At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p=0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p<0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p=0·045) favouring radiotherapy. Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89). The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each). Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group. There were no treatment-related deaths in either group., Interpretation: Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months. While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions., Funding: Fondazione Radioterapia Oncologica., Competing Interests: Declaration of interests IM has received occasional fees for advisory board participation supported by Eli Lilly, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini StemLine, outside the submitted work. ML has reported advisory roles supported by Roche, Eli Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini StemLine; speaker honoraria from Roche, Eli Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Knight, Daiichi Sankyo, Gilead, and Menarini StemLine; and travel grants from Gilead, Daiichi Sankyo, and Roche. VS has reported honoraria from Nucletron and Elekta. TS discloses unrestricted grants for programmes of Europa Donna Slovenia, as well as speaker honoraria from Pfizer, MSD, Roche, and AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Whole-slide imaging (WSI) has been adopted in many fields of pathology for education, quality assurance, and remote diagnostics. In 2021, the College of American Pathologists (CAP) updated guidelines to support pathology laboratories regarding the WSI systems validation process. However, the majority of published literature refers to histopathology rather than cytology. The aim of this study was to compare conventional light microscopy (CLM) and WSI in thin-layer cervical samples evaluation according to CAP guideline., Methods: A sample set of 64 thin-layer cervical specimens from women 25-64 years old who participated in cervical cancer screening programs in Tuscany was distributed among five cytologists at Institute for Cancer Research, Prevention and Clinical Network (Florence, Italy) for CLM analysis. After 2 weeks, the corresponding 64 digitally scanned slides were available at several magnifications for WSI evaluation., Results: Substantial/near perfect agreement between CLM and WSI evaluation (0.77 ≥ κ ≥1) was observed for the negative for intraepithelial lesion or malignancy (NILM) class with concordance rates from 83.3% to 100%.Variability in concordance was observed among all the cytologists: 50%-85.7% for low-grade squamous intraepithelial lesion (LSIL), 47.1%-100% for high-grade squamous intraepithelial lesion (HSIL), 50%-100% for atypical glandular cells (AGCs) favors adenocarcinoma (ADK) with moderate/near perfect agreement (0.47 ≥ κ ≥1). Concordance and agreement rates were also variable within the "borderline" cytological categories of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells cannot exclude an HSIL (ASC-H), and AGCs with lower or not computable kappa for some readers. The overall intralaboratory concordance between CLM and WSI was 92.9% with a near perfect agreement (κ = 0.84) for NILM. Substantial agreement (κ ≥0.65) was assessed for LSIL, HSIL/squamous cell carcinoma, AGCs, and ADK categories whereas the agreement was lower (κ ≤0.39) for ASC-US and ASC-H., Conclusions: This study showed an overall substantial/near perfect agreement between CLM and WSI for all the cytological categories except the "borderline" ASC-US and ASC-H. Further progress in cytology WSI systems are needed before introducing it in routine diagnostics., (© 2024 American Cancer Society.)

Background: Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain., Methods: A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline). Proportional hazards models were fitted in 245,699 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to identify robust environmental predictors. Polygenic risk scores (PRS) of 5 proxies of adiposity [BMI, WHR, and three body shape phenotypes (PCs)] were computed using genetic weights from an independent cohort (UK Biobank). Environmental and genetic models were validated in 29,953 EPIC participants., Findings: Environmental models presented a remarkable predictive ability (AUC BMI : 0.69, 95% CI: 0.68-0.70; AUC WHR : 0.75, 95% CI: 0.74-0.77). The genetic geographic distribution for WHR and PC1 (overall adiposity) showed higher predisposition in North than South Europe. Predictive ability of PRSs was null (AUC: ∼0.52) and did not improve when combined with environmental models. However, PRSs of BMI and PC1 showed some prediction ability for BMI gain from self-reported BMI at 20 years old to baseline observation (early adulthood) (AUC: 0.60-0.62)., Interpretation: Our study indicates that environmental models to discriminate European individuals at higher risk of adiposity gain can be integrated in standard prevention protocols. PRSs may play a robust role in predicting adiposity gain at early rather than mid-late adulthood suggesting a more important role of genetic factors in this life period., Funding: French National Cancer Institute (INCA&#95;N°2019-176) 1220, German Research Foundation (BA 5459/2-1), Instituto de Salud Carlos III (Miguel Servet Program CP21/00058)., Competing Interests: Declaration of interests L.M. discloses that an immediate family member holds stocks in Novo Nordisk. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Mycotoxins have been hypothesized to contribute to a diversity of adverse health effects in humans, even at low concentrations. Certain mycotoxins are established human carcinogens, whereas for others research suggests potential carcinogenic effects. The aim of this study was to determine the association between dietary exposure to mycotoxins and hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. EPIC questionnaire data were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority to assess long-term dietary mycotoxin exposure (expressed as μg/kg body weight/day) and then relate them to the risk of hepatocellular carcinoma (HCC) (n = 255) and biliary tract cancers (n = 273). Analyses were conducted using multivariable Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (95% CI). Key food groups contributing to mycotoxin exposure were cereals and cereal-based products, vegetables, non-alcoholic beverages (including fruit juices) and fruits. Estimated intake of deoxynivalenol (DON) and its derivatives was positively associated with HCC risk (HRT3vsT1: 1.90, 95% CI: 1.18-3.05, p-trend <0.01). No statistically significant associations were found for the other mycotoxins. Further research to confirm our observations and investigate potential underlying mechanisms of these compounds is warranted. These data may provide evidence of HCC risks associated with higher dietary intake levels of DON, which has not yet been classified as a human carcinogen., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huybrechts et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective : Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods : We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction. Results : Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes ( p < 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16-3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09-0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing. Conclusions : The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.

Objective: This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT)., Materials and Methods: Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software., Results: In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage., Conclusion: Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events., Competing Interests: Declarations. Conflict of interest: Icro Meattini declares occasional small fees received for advisory boards supported by Eli Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, Gilead, SeaGen, Pfizer, and Menarini StemLine. Roberto Pellegrini is an employee of Elekta AB (Stockholm, Sweden). Isacco Desideri, Jacopo Nori, and Lorenzo Livi are editors in this journal. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Florence. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication., (© 2024. Italian Society of Medical Radiology.)

Background and Objective: Psychosis represents one of the most challenging clinical presentations in psychiatry. Schizophrenia and bipolar disorder may both present psychotic features, and cariprazine may offer improvement in the treatment and care of these conditions. Therefore, the objective of the current work was to synthesise results of efficacy for cariprazine in these disorders., Methods: In total, five electronic databases were searched for randomized controlled trials enrolling patients across the psychosis spectrum, using the search term 'Cariprazine' (PubMed, Embase, clinicaltrials.gov, EUDRACT, Cochrane-last search January 2024). No filter or limits were employed. Effect sizes were extracted, by the mean difference in psychometric variables before and after the intervention (Clinical Global Impression Scale, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, Hamilton Anxiety Rating Scale)., Results: In total, 12 studies enrolling either patients with schizophrenia or bipolar disorder were included (total n = 6477; n = 4814 patients treated with cariprazine, n = 1663 controls treated with placebo). Cariprazine was effective in reducing global clinical severity, and higher improvements were observed at increasing dosages (- 0.25 at ≤ 1.5 mg/day, - 0.45 at ≥ 3 mg/day). Cariprazine also effectively reduced psychotic total scores: - 6.74, [95% confidence interval (CI) - 8.31; - 5.17], depression: - 1.78, [95% CI - 2.54; - 1.02], mania: - 5.72, [95% CI - 6.95; - 4.49], and anxiety symptoms: - 1.24, [95% CI - 1.92; - 0.56]., Conclusions: Cariprazine was observed as efficacious across retrieved studies, offering a potential for tailored treatments across the psychosis spectrum., Registration Number: https://osf.io/pmyhq ., (© 2024. The Author(s).)

A guideline panel formulated a set of recommendations for breast cancer screening and diagnosis to implement clinical activities in Italy in alignment with the European Breast Cancer Guidelines on Screening and Diagnosis (European Commission Initiative on Breast Cancer-ECIBC). The panel issued national recommendations through adopting, adapting, and/or developing recommendations from the European guidelines (ADOLOPMENT approach). This process utilizes the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence to decision (EtD) framework. An additional PubMed search was conducted using search terms specific to Italy to tailor the EU guidelines to the national context. Nine articles were included as contextual evidence in the EtD. A total of 13 recommendations were finalized, either adapted or adopted to suit the national context. Organized breast cancer screening is strongly recommended for women aged 50-69 every 2 years, and it is conditionally recommended every 3 years for women aged 70-74, as well as every 1 or 2 years for women aged 45-49. Annual mammography received a strong recommendation against for women aged 50 and older. Developing shared national guidelines for the management of mammography screening will improve the standardization of processes across all settings, thereby promoting health equity., Competing Interests: Declarations. Conflict of interest: Silvia Deandrea is the President of the Italian Mammography Screening Group; Marco Rosselli Del Turco was a medical consultant for senology at FORA s.p.a. Paolo Giorgi Rossi is a member of the panel that developed the European guidelines on breast cancer screening and diagnosis, referred document for the ADOLOPMENT process; Livia Giordano is a member of the panel that developed the European guidelines on breast cancer screening and diagnosis, referred document for the ADOLOPMENT process; Elena Parmelli was a contract staff member at the Joint Research Centre (JRC) of the European Commission, Ispra, VA (Italy); Cannatà Vittorio has been Vice-President of the Italian Association of Medical Physics (AIFM); Isabella Castellano has been professional consultant for symposium “Choosing the best therapy in ER + /HER2- breast cancer” (Token of attendance at the National Congress of Anatomic Pathology, October 2019), Myriad Genetics, s.r.l.; Stefano Pacifici is the President of the Italian Association of Senology Radiographers (AITeRS); Trianni Annalisa is a member of the Italian Association of Medical Physics (AIFM); Paola Golinelli was reimbursed for participation in the European Federation of Organization for Medical Physics (EFOMP) Working Group on mammographic tomosynthesis equipment. Pierpaolo Pattacini received a software by I-CAD. The other authors have no relevant financial or non-financial interest to disclose. Competing interests: All panellists were required to disclose all financial, non-financial, personal, and institutional interests relevant to the scope of the guidelines by completing a standardized form, following SNLG guidance. The Scientific Committee (SC) assessed each individual interest, and ultimately, no panellist was excluded from the voting procedures. This policy was upheld throughout the entire process, including the selection of panel members, the generation and prioritization of research questions, and participation in the formulation of recommendations. The SC consistently monitored the declaration of conflicts of interest (COI). Ethical approval: Ethical approval was not necessary for this kind of scientific work. Informed consent: Not applicable., (© 2024. Italian Society of Medical Radiology.)

Background: Lung cancer ranks as the leading cause of cancer-related deaths worldwide. There is evidence that second-hand smoke (SHS) exposure is a risk factor for the development of lung cancer in never-smokers. This systematic review and meta-analysis aims to provide the most accurate quantification of the association between SHS exposure and lung cancer risk in never-smokers., Materials and Methods: Through the use of an innovative method to identify original publications, we conducted a systematic review of the literature, with corresponding meta-analysis, of all epidemiological studies evaluating the association between SHS exposure and lung cancer risk among never-smokers, published up to May 2023. Pooled relative risks were obtained using random-effects models. Dose-response relationships were derived using log-linear functions or cubic splines., Results: Out of 126 identified eligible studies, 97 original articles were included in the meta-analysis. The pooled relative risk for lung cancer for overall exposure to SHS was 1.24 (95% CI 1.16-1.32, number of articles, n=82). Setting-specific relative risks were 1.20 (95% CI 1.12-1.28, n=67) for SHS exposure at home, 1.38 (95% CI 1.28-1.62, n=30) at a workplace, 1.37 (95% CI 1.22-1.53, n=28) at home or a workplace and 1.27 (95% CI 1.11-1.44, n=24) in nonspecified settings. The risk of lung cancer significantly increased with the duration, intensity and pack-years of SHS exposure., Conclusions: This meta-analysis shows that exposure to SHS increases by more than 20% the risk of lung cancer among never-smokers, providing definitive evidence of the association between SHS exposure and lung cancer risk., Competing Interests: Conflict of interest: All authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright ©The authors 2024.)

Background: Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality., Objectives: Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework., Methods: A nested case-control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics., Results: Thirteen microbial metabolites were identified nominally associated with PD risk (P-value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD-associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals., Conclusion: Changes in microbial metabolites may represent a pre-diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Comprehensive legislation covering the use of all types of tobacco and nicotine products to provide a smoke- and aerosol-free environment (SAFE) should be part of strategies aimed at phasing out tobacco use. There is a need to identify challenges and opportunities for advancing SAFE policies and their implementation. This study aims to identify barriers and opportunities to extend, enforce, and comply with SAFE policies in Europe., Methods: Within the Joint Action on Tobacco Control 2, a cross-sectional expert consultation was launched in 2022. Data obtained through an online questionnaire including closed and open-ended questions on barriers, opportunities, and interference by the tobacco and/or nicotine industry (TNI) on the extension, and compliance with/enforcement of SAFE policies, were analyzed thematically and descriptively., Results: From 29 European countries, 61 experts (response rate: 55.5%) were included in our sample. The most commonly identified barriers for the extension of SAFE policies were tobacco industry lobbying and funding activities, while the most commonly reported opportunity was extending SAFE policies to specific outdoor public or private places, especially where children are present. In terms of compliance with/enforcement of SAFE policies, the lack of human and financial resources and capacity to monitor/enforce compliance were the most commonly identified barriers, while opportunities included more powerful enforcement authorities with increased capacity. The experts identified greater TNI interference on the extension than on the enforcement of SAFE policies., Conclusions: Comprehensive regulation of TNI interference and allocation of human/financial resources for policy enforcement, should be a priority for the extension of SAFE policies in Europe., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Pénzes M. et al.)

Introduction: Several studies have described how the restrictive measures due to COVID-19 have delayed melanoma diagnoses, resulting in an increased rate of more severe cases. Summarizing the sparse results in this context might help to understand the real impact of the COVID-19 pandemic on melanoma. We conducted a systematic review and meta-analysis to investigate how the clinical and prognostic factors of new melanoma diagnoses changed after COVID-19., Methods: A literature search in MEDLINE, EMBASE, and Scopus was conducted in September 2023. We included studies published in peer-reviewed journals reporting histopathological data on new diagnoses of cutaneous melanoma in adult patients during and/or after the lockdown compared to those diagnosed before the COVID-19 pandemic. A meta-analysis was conducted utilizing a random effects model. The between-study heterogeneity was assessed via Higgins's I 2 statistic. Publication bias was assessed using the Begg and Egger test. This study adhered to the updated PRISMA guidelines. The primary outcome was a comparison of melanoma thickness between the pre-COVID-19 and post-lockdown periods. The secondary outcomes were evaluations of the histopathological subtype, stage, and presence of ulceration and mitosis in melanomas diagnosed in these two pandemic phases., Results: The study included 45 articles. We found a significantly higher proportion of all factors indicating worse prognosis in the post-lockdown period compared to the pre-COVID-19 phase, including high thickness (SOR = 1.14, 95%CI 1.08-1.20 for 1-2 mm; SOR = 1.62, 95%CI 1.08-2.40, for >2 mm), the presence of ulcerations (SOR = 1.35, 95%CI 1.18-1.54), nodular subtype (SOR = 1.19, 95%CI 1.07-1.32), the presence of mitosis (SOR = 1.57, 95% CI 1.17-2.11), and stage III (SOR = 1.39, 95%CI 1.19-1.52) and IV (SOR = 1.44, 95%CI 1.26-1.63). Limitations include the limited studies' geographical distribution and moderate heterogeneity affecting meta-analysis estimates., Conclusions: Our meta-analysis provided evidence of more advanced melanomas diagnosed in the post-COVID-19 pandemic period, emphasizing the importance of creating and updating pandemic preparedness plans to limit the impact of any future events on oncological care.

Background: Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive., Methods: We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors., Results: Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR 1-SD 1.25, 95% CI 1.07-1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR 1-SD 1.41, 95% CI 1.18-1.69) and BC-specific mortality (HR 1-SD 1.31, 95% CI 1.03-1.66), (P Heterogeneity (pre/postmenopausal)  < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR 1-SD 1.19, 95% CI 1.02-1.40 and HR 1-SD 1.28, 95% CI 1.06-1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR 1-SD 1.35, 95% CI 1.10-1.65 and HR 1-SD 1.42 95% CI 1.08-1.86), while TNF-α was associated with all-cause mortality in HER2- (HR 1-SD 1.31, 95% CI 1.07-1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR 1-SD 1.30, 95% CI 1.07-1.58)., Conclusions: Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality., (© 2024. The Author(s).)

Radiomics of cardiac magnetic resonance (MR) imaging has proved to be potentially useful in the study of various myocardial diseases. Therefore, assessing the repeatability degree in radiomic features measurement is of fundamental importance. The aim of this study was to assess test-retest repeatability of myocardial radiomic features extracted from quantitative T1 and T2 maps. A representative group of 24 subjects (mean age 54 ± 18 years) referred for clinical cardiac MR imaging were enrolled in the study. For each subject, T1 and T2 mapping through MOLLI and T2-prepared TrueFISP acquisition sequences, respectively, were performed at 1.5 T. Then, 98 radiomic features of different classes (shape, first-order, second-order) were extracted from a region of interest encompassing the whole left ventricle myocardium in a short axis slice. The repeatability was assessed performing different and complementary analyses: intraclass correlation coefficient (ICC) and limits of agreement (LOA) (i.e., the interval within which 95% of the percentage differences between two repeated measures are expected to lie). Radiomic features were characterized by a relatively wide range of repeatability degree in terms of both ICC and LOA. Overall, 44.9% and 38.8% of radiomic features showed ICC values > 0.75 for T1 and T2 maps, respectively, while 25.5% and 23.4% of radiomic features showed LOA between ±10%. A subset of radiomic features for T1 (Mean, Median, 10Percentile, 90Percentile, RootMeanSquared, Imc2, RunLengthNonUniformityNormalized, RunPercentage and ShortRunEmphasis) and T2 (MaximumDiameter, RunLengthNonUniformityNormalized, RunPercentage, ShortRunEmphasis) maps presented both ICC > 0.75 and LOA between ±5%. Overall, radiomic features extracted from T1 maps showed better repeatability performance than those extracted from T2 maps, with shape features characterized by better repeatability than first-order and textural features. Moreover, only a limited subset of 9 and 4 radiomic features for T1 and T2 maps, respectively, showed high repeatability degree in terms of both ICC and LOA. These results confirm the importance of assessing test-retest repeatability degree in radiomic feature estimation and might be useful for a more effective/reliable use of myocardial T1 and T2 mapping radiomics in clinical or research studies., Competing Interests: Declaration of competing interest The Authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Literature indicates a potential association between dairy consumption and risk of Parkinson´s disease (PD), especially among men, yet the results remain inconclusive. We investigated this association in a large prospective European cohort. Dietary and non-dietary data was collected from 183,225 participants of the EPIC-for-Neurodegenerative-Diseases (EPIC4ND) cohort, a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Crude and multivariable-adjusted Cox proportional hazards models were employed to examine potential associations between baseline dietary intake of dairy, calcium and vitamin D with incident PD risk. No relationship was observed between dairy consumption (HR 1.07, 95% CI 0.82-1.39), individual dairy products (milk: HR 0.95, 95% CI 0.73-1.23; yogurt: HR 1.03, 95% CI 0.82-1.29; cheese: HR 1.13, 95% CI 0.85-1.51), or vitamin D (HR 1.08, 95% CI 0.80-1.45) with PD risk. However, we observed a risk-increasing association with higher calcium intakes (HR 1.33, 95% CI 1.00-1.78, p for trend = 0.031), which was more pronounced in men (HR 1.50, 95% CI 1.00-2.25, p for trend = 0.044) and in ever smokers (HR 1.64, 95% CI 1.06-2.53, p for trend = 0.014). No compelling evidence was found for an association between dairy products or vitamin D intake and PD risk indicating a potentially limited relevance of dairy intake in PD risk than previously described. Our observations of a positive association between dietary calcium intake and PD risk in men and in ever smokers require further validation., Competing Interests: Declarations. Ethical approval: The studies involving human participants were reviewed and approved by IARC Ethics Committee (IEC). Consent to participate: The patients/participants provided their written informed consent to participate in this study. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organisation, the authors alone are responsible for the view expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Aims/hypothesis: The aim of the present study was to investigate the association between dietary exposures to dioxins, dioxin-like polychlorinated biphenyls (DL-PCBs) and non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and the incidence of type 2 diabetes mellitus (T2DM) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: This prospective cohort study with a median 11.7 years of follow-up, included 318,416 individuals recruited in 21 centers in eight countries. Dietary intake of dioxins and PCBs was calculated by combining EPIC food consumption data with food contamination data from the European Food Safety Authority (EFSA). To identify incident cases of T2DM, a thorough review of various sources including self-reported information, linkage to primary and secondary care registers, drug registers, hospital admissions, and mortality data was conducted. Associations between dietary intake of dioxins and PCBs and T2DM were evaluated using multivariable Cox regressions., Results: Higher T2DM risk was observed for higher estimated dietary intake of non-dioxin-like PCBs (NDL-PCBs; HR per 1 SD increment = 1.03 [95 %CI 1.01;1.04], and HR (Q4 = 1.15 [1.08;1.22], P-trend < 0.001). The results were consistent in analyses stratified by gender, body mass index, country, median follow-up, or self-reported hypertension and hyperlipidemia, as well as when adjusting for fat intake. No consistent association was observed between dioxins+DL-PCBs intake and T2DM risk.vs Q1) = 1.15 [1.08;1.22], P-trend < 0.001). The results were consistent in analyses stratified by gender, body mass index, country, median follow-up, or self-reported hypertension and hyperlipidemia, as well as when adjusting for fat intake. No consistent association was observed between dioxins+DL-PCBs intake and T2DM risk., Conclusion / Interpretation: Results obtained in this large European prospective study indicate a positive and linear association between dietary intake of NDL-PCBs and risk of T2DM. This association remained consistent across various stratified and sensitivity analyses. Further studies are warranted to better understand the biological mechanisms underlying this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Over the past decade, several randomized controlled trials have compared single-day dexamethasone (dexamethasone-sparing) regimens to the current standard multi-day dexamethasone antiemetic regimen for chemotherapy-induced nausea and vomiting (CINV). The aim of this systematic review and meta-analysis is to compare the efficacy and safety of dexamethasone-sparing regimens to standard multi-day dexamethasone, used for the prophylaxis of CINV., Methods: Ovid Medline and Embase were searched from database inception to March 2024. Studies were included if they reported on randomized controlled trials of adult cancer patients receiving different scheduling of dexamethasone, for the endpoints of complete response, complete control, no nausea, no vomiting, and no use of rescue medication. Safety was also assessed. Meta-analysis, leave-one-out meta-analysis, and cumulative meta-analysis were conducted to generate summary effect estimates and assess the influence of single trials on the summary effect estimate., Results: Ten trials reporting on 2234 patients were included. Dexamethasone-sparing regimens were found to be no different to control arm in the acute (Risk Ratio [RR] 1.01; 95% CI, 0.94-1.08), delayed (RR 0.97; 95% CI, 0.89-1.05) and overall phases (RR 0.98; 95% CI, 0.90-1.06) for complete response. There was likewise no difference for complete control, no nausea, no vomiting, and no use of rescue medication. Safety profile was similar. There was no concern for bias in the published literature. No difference was found between studies reporting on anthracycline/cyclophosphamide-based highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC)., Conclusion: In this comprehensive systematic review and meta-analysis, dexamethasone-sparing regimens were found to be no different to current multi-day regimens with respect to efficacy and safety for MEC and anthracycline/cyclophosphamide-based regimens. Clinicians and future guidelines should strongly consider greater adoption and endorsement of dexamethasone-sparing regimens., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Smoke-free legislation has been shown to positively impact reducing secondhand smoke (SHS) exposure, especially in countries that have implemented comprehensive legislation rather than partial bans. Also, secondhand aerosols (SHA) that come from the heating of tobacco or liquids, with or without nicotine, in electronic nicotine delivery systems (ENDS) have been proven to increase levels of harmful substances in the air. Therefore, protection against SHS and SHA exposure and expansion of smoke- and aerosol-free environments (SAFE) should be taken into account when creating or trying to expand or enforce clean air policies. This article aims to present the protocol for a consultation with experts on tobacco and nicotine control in order to identify best practices, barriers, and opportunities for the expansion of SAFE in Europe. We identified experts among policymakers, researchers, and tobacco regulators in European countries and invited them to participate in the consultation by completing an online survey designed, programmed, and pilot-tested using Survey Monkey. The responses to the questionnaire contained quantitative and qualitative information that was thematically analyzed. The experts' consultation allowed us to produce a report on barriers and opportunities for SAFE, a report and a position paper on SAFE best practices, a web-based repository of best practices, and a weight of evidence paper that assembles evidence supporting the expansion of SAFE on indoor and outdoor spaces., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Carnicer-Pont D. et al.)

Background: A large fraction of the disease burden in the Italian population is due to behavioral risk factors. The objective of this work is to provide a tool to estimate the impact of preventive interventions that reduce the exposure to smoking and sedentary lifestyle of the Italian population, with the goal of selecting optimal interventions., Methods: We construct a Markovian model that simulates the state of each subject of the Italian population. The model predicts the distribution of subjects in each health status and risk factor status for every year of the simulation. Based on this distribution, the model provides a rich output summary, such as the number of incident and prevalent cases for each tracing disease and the Disability Adjusted Life Years (DALY), used to assess the impact of preventive interventions, and how this impact is shaped in time., Results: This paper focuses on the methodological aspects of the model. The proposed model is flexible and can be applied to estimate the impact of complex interventions on the two risk factors and adapted to consider different cohorts. We validate the model by simulating the evolution of the Italian population from 2009 to 2017 and comparing the output with historical data. Furthermore, as a case-study, we simulate a counterfactual scenario where both tobacco and sedentary lifestyle are eradicated from the Italian population in 2019 and estimate the impact of such intervention over the following 20 years., Conclusions: We propose a Markovian model to estimate how interventions on smoking and sedentary lifestyle can affect the reduction of the disease burden, and validate the model on historical data. The model is flexible and allows to extend the analysis to consider more risk factors in future research. However, we are aware that, given the ever-increasing availability of data, it is necessary in the future to increase the complexity of the model, to be closer to reality and to provide decision-making support to the policy-makers., (© 2024. The Author(s).)

Background: Lung cancer (LC) is among the most common neoplasms, mostly caused by smoking. This study, carried out within the ACAB project, aims to provide local, updated and systematic estimates of years lived with disability (YLD) from LC due to smoking in the Tuscany region, Italy., Methods: We estimated YLD for the year 2022 for the whole region and at subregional level by local health unit (LHU) using data from the Tuscany Cancer Registry and local surveys. YLD were calculated by applying the severity-specific LC prevalence, estimated with an incidence-based disease model, to the corresponding disability weight. The burden from smoking was computed by: modelling the prevalence of smokers with a Bayesian Dirichlet-Multinomial regression model; estimating the distribution of smokers by pack-years simulating individual smoking histories; collecting relative risks from the literature., Results: In 2022 in Tuscany, LC caused 7.79 (95% uncertainty interval [UI] = 2.26, 17.27) and 25.50 (95% UI = 7.30, 52.68) YLDs per 100,000 females and males, respectively, with slight variations by LHU, and 53% and 66% of the YLDs were caused by smoking., Conclusion: The updated estimates of the burden of LC attributable to smoking for the Tuscany region as a whole and for each LHU provide indications to inform strategic prevention plans and set public health priorities. The impact of smoking on YLDs from LC is not negligible and heterogeneous by LHU, thus requiring local interventions., (© 2024. The Author(s).)

Background and Aim: Lead (Pb) is a toxic heavy metal and pervasive environmental contaminant, and a class 2 A carcinogen according to the IARC classification, yet its link with cancer at several body sites remains uncertain. Here, we aimed at summarizing the scientific evidence regarding its association with cancer risk and mortality, focusing on studies that carried out Pb measurements in biological samples., Methods: We reviewed articles published in PubMed and EMBASE until January 2nd, 2024, that quantified the epidemiological association between Pb measured in blood, urine, nails, and other biological media, and cancer risk and mortality (overall and by cancer site/type)., Results: We included 46 articles (out of 8022 screened) published in 1995-2023 and reporting on investigations conducted in fifteen countries. In terms of design, 20 were prospective, 24 were retrospective case-control studies, and 2 were cross-sectional. Pb levels were determined in blood in the majority of studies (n=28). The most consistent evidence was for the association of Pb with cancer of the gastrointestinal tract, particularly the oesophagus, stomach (RR ranging from 0.80 to 2.66), colon-rectum, and pancreas; and of the bladder and urinary tract (RR from 1.10 to 2.89). For other specific malignancies, the data were conflicting or too limited to draw reliable conclusions. Finally, increased Pb concentration in blood and urine was consistently associated with higher overall cancer incidence and mortality., Conclusions: Lead is a widespread and highly persistent environmental pollutant associated with cancer at multiple body sites. Comprehensive primary prevention interventions aiming at reducing opportunities for Pb exposure need to be continuously promoted and implemented., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear., Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls)., Findings: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk., Interpretation: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis., Funding: Funding for IIG&#95;FULL&#95;2021&#95;008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA&#95;15849 was obtained from Institut National du Cancer (INCa)., Competing Interests: Declaration of interests EJC is the president of the Peaches Womb Cancer Trust and the research advisory committee chair of the Eve Appeal, both roles are voluntary and unpaid. All other authors declare no conflicts of interest., (Copyright © 2024 World Health Organization. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials., Methods: Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3-5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization., Results: LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive)., Conclusions: LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)