The Impact of Russia-Ukraine geopolitical conflict on the air quality and toxicological properties of ambient PM2.5 in Milan, Italy.

The geopolitical conflict between Russia and Ukraine has disrupted Europe's natural gas supplies, driving up gas prices and leading to a shift towards biomass for residential heating during colder months. This study assessed the consequent air quality and toxicological impacts in Milan, Italy, focusing on fine particulate matter (PM2.5, dp < 2.5 µm) emissions. PM2.5 samples were analyzed for their chemical composition and assessed for their oxidative potential using the dithiothreitol (DTT) assay across three periods reflecting residential heating deployment (RHD): pre-RHD, intra-RHD, and post-RHD periods. During the intra-RHD period, PM2.5 levels were significantly higher than those in other periods, with concentrations reaching 57.94 ± 7.57 µg/m3, indicating a deterioration in air quality. Moreover, levoglucosan was 9.2 times higher during the intra-RHD period compared to the pre-RHD period, correlating with elevated levels of elemental carbon (EC) and polycyclic aromatic hydrocarbons (PAHs). These findings were compared with previous local studies before the conflict, underscoring a significant rise in biomass-related emissions. DTT assay levels during the intra-RHD were 2.1 times higher than those observed during the same period in 2022, strongly correlating with biomass burning emissions. Our findings highlight the necessity for policies to mitigate the indirect health effects of increased biomass burning emissions due to the energy crisis triggered by the geopolitical conflict.

Implant replacement and anaplastic large cell lymphoma associated with breast implants: a quantitative analysis.

Introduction: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma associated with breast reconstruction post-mastectomy or cosmetic-additive mammoplasty. The increasing use of implants for cosmetic purposes is expected to lead to an increase in BIA-ALCL cases. This study investigated the main characteristics of the disease and the factors predicting BIA-ALCL onset in patients with and without an implant replacement. Methods: A quantitative analysis was performed by two independent researchers on cases extracted from 52 primary studies (case report, case series, and systematic review) published until April 2022 and searched in PubMed, Scopus, and Google-Scholar databases using "Breast-Implant" AND/OR "Associated" AND/OR "Anaplastic-Large-Cell-Lymphoma". The statistical significance was verified by Student's t-test for continuous variables, while Fisher's exact test was applied for qualitative variables. Cox model with time-dependent covariates was used to estimate BIA-ALCL's onset time. The Kaplan-Meier model allowed the estimation of the probability of survival after therapy according to breast implant exposure time. Results: Overall, 232 patients with BIA-ALCL were extracted. The mean age at diagnosis was 55 years old, with a mean time to disease onset from the first implant of 10.3 years. The hazard of developing BIA-ALCL in a shorter time resulted significantly higher for patients not having an implant replacement (hazard ratio = 0.03; 95%CI: 0.005-0.19; p-value < 0.01). Patients with implant replacement were significantly older than patients without previous replacement at diagnosis, having a median time to diagnosis since the first implant of 13 years (7 years in patients without replacement); anyway, the median time to BIA-ALCL occurrence since the last implantation was equal to 5 years. Discussion: Our findings suggest that, in BIA-ALCL patients, the implant substitution and/or capsulectomy may delay the disease's onset. However, the risk of reoccurrence in an earlier time should be considered in these patients. Moreover, the time to BIA-ALCL onset slightly increased with age. Selection bias, lack of awareness, misdiagnosis, and limited data availability could be identified as limits of our study. An implant replacement should be considered according to a risk stratification approach to delay the BIA-ALCL occurrence in asymptomatic patients, although a stricter follow-up after the implant substitution should be recommended. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023446726.

Causes of death in women with breast cancer: a risks and rates study on a population-based cohort.

Introduction: The increasing survival of patients with breast cancer has prompted the assessment of mortality due to all causes of death in these patients. We estimated the absolute risks of death from different causes, useful for health-care planning and clinical prediction, as well as cause-specific hazards, useful for hypothesis generation on etiology and risk factors. Materials and methods: Using data from population-based cancer registries we performed a retrospective study on a cohort of women diagnosed with primary breast cancer. We carried out a competing-cause analysis computing cumulative incidence functions (CIFs) and cause-specific hazards (CSHs) in the whole cohort, separately by age, stage and registry area. Results: The study cohort comprised 12,742 women followed up for six years. Breast cancer showed the highest CIF, 13.71%, and cardiovascular disease was the second leading cause of death with a CIF of 3.60%. The contribution of breast cancer deaths to the CIF for all causes varied widely by age class: 89.25% in women diagnosed at age <50 years, 72.94% in women diagnosed at age 50-69 and 48.25% in women diagnosed at age ≥70. Greater CIF variations were observed according to stage: the contribution of causes other than breast cancer to CIF for all causes was 73.4% in women with stage I disease, 42.9% in stage II-III and only 13.2% in stage IV. CSH computation revealed temporal variations: in women diagnosed at age ≥70 the CSH for breast cancer was equaled by that for cardiovascular disease and "other diseases" in the sixth year following diagnosis, and an early peak for breast cancer was identified in the first year following diagnosis. Among women aged 50-69 we identified an early peak for breast cancer followed by a further peak near the second year of follow-up. Comparison by geographic area highlighted conspicuous variations: the highest CIF for cardiovascular disease was more than 70% higher than the lowest, while for breast cancer the highest CIF doubled the lowest. Conclusion: The integrated interpretation of absolute risks and hazards suggests the need for multidisciplinary surveillance and prevention using community-based, holistic and well-coordinated survivorship care models.

Comparison between two cancer registry quality check systems: functional features and differences in an Italian network of cancer registries dataset.

Purpose: The aim of this study was to compare the functional characteristics of two computer-based systems for quality control of cancer registry data through analysis of their output differences. Methods: The study used cancer incidence data from 22 of the 49 registries of the Italian Network of Cancer Registries registered between 1986 and 2017. Two different data checking systems developed by the WHO International Agency for Research on Cancer (IARC) and the Joint Research Center (JRC) with the European Network of Cancer Registries (ENCR) and routinely used by registrars were used to check the quality of the data. The outputs generated by the two systems on the same dataset of each registry were analyzed and compared. Results: The study included a total of 1,305,689 cancer cases. The overall quality of the dataset was high, with 86% (81.7-94.1) microscopically verified cases and only 1.3% (0.03-3.06) cases with a diagnosis by death certificate only. The two check systems identified a low percentage of errors (JRC-ENCR 0.17% and IARC 0.003%) and about the same proportion of warnings (JRC-ENCR 2.79% and IARC 2.42%) in the dataset. Forty-two cases (2% of errors) and 7067 cases (11.5% of warnings) were identified by both systems in equivalent categories. 11.7% of warnings related to TNM staging were identified by the JRC-ENCR system only. The IARC system identified mainly incorrect combination of tumor grade and morphology (72.5% of warnings). Conclusion: Both systems apply checks on a common set of variables, but some variables are checked by only one of the systems (for example, checks on patient follow-up and tumor stage at diagnosis are included by the JRC-ENCR system only). Most errors and warnings were categorized differently by the two systems, but usually described the same issues, with warnings related to "morphology" (JRC-ENCR) and "histology" (IARC) being the most frequent. It is important to find the right balance between the need to maintain high standards of data quality and the workability of such systems in the daily routine of the cancer registry.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

[Global evaluation of the mortality and hospitalization in the Italian contaminated sites included in the SENTIERI project]. / Stime globali della mortalità e ospedalizzazione nei siti contaminati italiani inclusi nel progetto SENTIERI.

Since 2006, epidemiological surveillance of populations living in Italian contaminated sites has been ongoing (SENTIERI Project). Updated global estimates of mortality (2013-2017) and hospitalization (2014-2018) are reported. The excess deaths (observed-expected) for the main groups of diseases were calculated for all the 46 sites together. Through a random-effect meta-analysis of the standardized mortality and hospitalization rates (SMR/SHR), the pooled SMR/SHR for all the sites and their groupings were estimated. In the 46 sites, 8,342 exceeding deaths (1,668/year) were estimated, 4,353 in males and 3,989 in females, resulting in an excess risk of 2% in both genders. The risk of hospitalization for all causes was in excess of 3%. These excesses are mainly attributable to malignant tumours. In subgroups of sites, exceeding SMRs were observed for all mesotheliomas and pleural mesotheliomas, lung and colorectal cancers in both genders. SHR for all causes were observed in excess in the first year of life (+8%), in the group 0-19 and 20-29 years (+3-5%); no excesses of mortality were observed in the group 0-29 years.

Influence of Sex and Age on Site of Onset, Morphology, and Site of Metastasis in Colorectal Cancer: A Population-Based Study on Data from Four Italian Cancer Registries.

The prognosis of colorectal cancer is affected by factors such as site of origin, tumor morphology, and metastasis at diagnosis, but also age and sex seem to play a role. This study aimed to investigate within the Italian population how sex and age interact in influencing certain aspects of the disease and how they affect patient survival, particularly in the metastatic cohort. Data from four cancer registries were collected, and patients were classified by sex and age (<50, 50-69, and >69 years). Two separate analyses were conducted: one for patients having right or left colon cancer with adenocarcinoma or mucinous morphology, and one for patients having metastases at diagnosis. Women showed significant differences in right colon cases from the youngest to oldest age group (36% vs. 45% vs. 60%). Men <50 years had a significantly higher mucinous carcinoma percentage than their female counterparts (22% vs. 11%), while in the oldest age group women had the highest percentage (15% vs. 11%). The metastatic pattern differed between men and women and by age. The three-year relative survival in the <50 age group was better for women than men, but this survival advantage was reversed in the oldest group. In conclusion, sex and age are factors that influence the biological and clinical characteristics of colorectal cancer, affecting the metastatic pattern as well as patient survival.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.

BACKGROUND: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. METHODS: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. RESULTS: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. CONCLUSIONS: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths.

An Epidemiological Study to Investigate Links between Atmospheric Pollution from Farming and SARS-CoV-2 Mortality.

Exposure to atmospheric particulate matter and nitrogen dioxide has been linked to SARS-CoV-2 infection and death. We hypothesized that long-term exposure to farming-related air pollutants might predispose to an increased risk of COVID-19-related death. To test this hypothesis, we performed an ecological study of five Italian Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna and Sicily), linking all-cause mortality by province (administrative entities within regions) to data on atmospheric concentrations of particulate matter (PM2.5 and PM10) and ammonia (NH3), which are mainly produced by agricultural activities. The study outcome was change in all-cause mortality during March-April 2020 compared with March-April 2015-2019 (period). We estimated all-cause mortality rate ratios (MRRs) by multivariate negative binomial regression models adjusting for air temperature, humidity, international import-export, gross domestic product and population density. We documented a 6.9% excess in MRR (proxy for COVID-19 mortality) for each tonne/km2 increase in NH3 emissions, explained by the interaction of the period variable with NH3 exposure, considering all pollutants together. Despite the limitations of the ecological design of the study, following the precautionary principle, we recommend the implementation of public health measures to limit environmental NH3 exposure, particularly while the COVID-19 pandemic continues. Future studies are needed to investigate any causal link between COVID-19 and farming-related pollution.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Molecular Subtypes, Metastatic Pattern and Patient Age in Breast Cancer: An Analysis of Italian Network of Cancer Registries (AIRTUM) Data.

Breast cancer stage at diagnosis, patient age and molecular tumor subtype influence disease progression. The aim of this study was to analyze the relationships between these factors and survival in breast cancer patients among the Italian population using data from the AIRTUM national database. We enrolled women with primary breast cancer from 17 population-based cancer registries. Patients were subdivided into older (>69 years), middle (50-69 years) and younger age groups (<50 years) and their primary tumors categorized into four molecular subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. There were 8831 patients diagnosed between 2010 and 2012 included. The most represented age group was 50-69 years (41.7%). In 5735 cases the molecular subtype was identified: HER2-/HR+ was the most frequent (66.2%) and HER2+/HR- the least (6.2%). Of the 390 women with metastases at diagnosis, 38% had simultaneous involvement of multiple sites, independent of age and molecular profile. In women with a single metastatic site, bone (20% of cases), liver (11%), lung (7%) and brain (3%) were the most frequent. In the studied age groups with different receptor expression profiles, the tumor metastasized to target organs with differing frequencies, affecting survival. Five-year survival was lowest in women with triple-negative (HER2-/HR-) tumors and women with brain metastases at diagnosis.

Variation of Cancer Incidence between and within GRELL Countries.

Variation in cancer incidence between countries and groups of countries has been well studied. However cancer incidence is linked to risk factors that may vary within countries, and may subsist in localized geographic areas. In this study we investigated between- and within-country variation in the incidence of all cancers combined for countries belonging to the Group for Cancer Epidemiology and Registration in Latin Language Countries (GRELL). We hypothesized that investigation at the micro-level (circumscribed regions and local cancer registry areas) would reveal incidence variations not evident at the macro level and allow identification of cancer incidence hotspots for research, public health, and to fight social inequalities. Data for all cancers diagnosed in 2008-2012 were extracted from Cancer Incidence in Five Continents, Vol XI. Incidence variation within a country or region was quantified as r/R, defined as the difference between the highest and lowest incidence rates for cancer registries within a country/region (r), divided by the incidence rate for the entire country/region × 100. We found that the area with the highest male incidence had an ASRw 4.3 times higher than the area with the lowest incidence. The area with the highest female incidence had an ASRw 3.3 times higher than the area with the lowest incidence. Areas with the highest male ASRws were Azores (Portugal), Florianopolis (Brazil), Metropolitan France, north Spain, Belgium, and north-west and north-east Italy. Areas with the highest female ASRws were Florianopolis (Brazil), Belgium, north-west Italy, north-east Italy, central Italy, Switzerland and Metropolitan France. Our analysis has shown that cancer incidence varies markedly across GRELL countries but also within several countries: the presence of several areas with high cancer incidence suggests the presence of area-specific risk factors that deserve further investigation.

Municipality Data as a Rapid and Effective Tool to Analyse Spatial and Temporal Variations of All-Cause Mortality by Town District: The Experience in Genoa (Italy).

The main objective of this study was to analyse the space-time epidemiological differences by sex during the 2009-2020 period in the total mortality recorded among residents in each of the 25 districts of the Genoa municipality, net of the age effect. The analysis was based on official statistical data relating to total mortality and on the resident population. An estimate of the expected deaths was made to calculate the sex-specific age-standardised mortality ratio (SMR). The temporal trends and age-standardized death rates (SDRs) with respect to those of the European population specific to sex and calendar year were identified for each district. Over the entire observation period, the SMR for males ranged from 124.4 (Cornigliano) to 82.0 (Albaro); for females, the values ranged between 133.4 (Cornigliano) and 85.6 (Nervi-Quinto-S. Ilario). Between 2019 and 2020, Genoa recorded an increase in SDR of 24.5%, more pronounced in males (+26.7%) than in females (+22.4%). This epidemiological methodology is replicable and allows to quickly identify spatial, temporal, sex, and age differences in the general mortality within a municipality.

Water and Soil Pollution: Ecological Environmental Study Methodologies Useful for Public Health Projects. A Literature Review.

Health risks at population level may be investigated with different types of environmental studies depending on access to data and funds. Options include ecological studies, case-control studies with individual interviews and human sample analysis, risk assessment or cohort studies. Most public health projects use data and methodologies already available due to the cost of ad-hoc data collection. The aim of the article is to perform a literature review of environmental exposure and health outcomes with main focus on methodologies for assessing an association between water and/or soil pollutants and cancer. A systematic literature search was performed in May 2019 using PubMed. Articles were assessed by four independent reviewers. Forty articles were identified and divided into four groups, according to the data and methods they used, i.e.: (1) regression models with data by geographical area; (2) regression models with data at individual level; (3) exposure intensity threshold values for evaluating health outcome trends; (4) analyses of distance between source of pollutant and health outcome clusters. The issue of exposure assessment has been investigated for over 40 years and the most important innovations regard technologies developed to measure pollutants, statistical methodologies to assess exposure, and software development. Thanks to these changes, it has been possible to develop and apply geo-coding and statistical methods to reduce the ecological bias when considering the relationship between humans, geographic areas, pollutants, and health outcomes. The results of the present review may contribute to optimize the use of public health resources.

Prevalence and mortality in children with congenital diaphragmatic hernia: a multicountry study.

PURPOSE: This study determined the prevalence, mortality, and time trends of children with congenital diaphragmatic hernia (CDH). METHODS: Twenty-five hospital- and population-based surveillance programs in 19 International Clearinghouse for Birth Defects Surveillance and Research member countries provided birth defects mortality data between 1974 and 2015. CDH cases included live births, stillbirths, or elective termination of pregnancy for fetal anomalies. Prevalence, cumulative mortality rates, and 95% confidence intervals (CIs) were calculated using Poisson regression and a Kaplan-Meier product-limit method. Joinpoint regression analyses were conducted to assess time trends. RESULTS: The prevalence of CDH was 2.6 per 10,000 total births (95% CI: 2.5-2.7), slightly increasing between 2001 and 2012 (average annual percent change = 0.5%; 95% CI:-0.6 to 1.6). The total percent mortality of CDH was 37.7%, with hospital-based registries having more deaths among live births than population-based registries (45.1% vs. 33.8%). Mortality rates decreased over time (average annual percent change = -2.4%; 95% CI: -3.8 to 1.1). Most deaths due to CDH occurred among 2- to 6-day-old infants for both registry types (36.3%, hospital-based; 12.1%, population-based). CONCLUSIONS: The mortality of CDH has decreased over time. Mortality remains high during the first week and varied by registry type.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

Incidence of Thyroid Cancer in Italian Contaminated Sites.

Some human literature suggests a possible role of endocrine disruptors (EDs) exposure in thyroid cancer (TC) development. We investigated TC incidence in selected Italian National Priority Contaminated Sites (NPCS) with documented presence of EDs considered thyroid carcinogens. Adjusted Standardized Incidence Ratios (SIRs), with their 90% confidence intervals, were computed by gender, and age-specific groups (aged 15-39 years, and 40 years or over) for each NPCS in the period 2006 to 2013. In the age group of 15-39 years, a significant excess of TC risk was found in two NPCSs in males; non-significant excess risks were observed in four NPCSs in males, and in five in females. In the age group of 40 years and over, significant excess risks were found in six NPCSs in males and in seven NPCSs in females; non-significant excess risks were identified in two NPCSs in males and females. The findings of several excesses in incidence, mainly observed in adults aged 40 years or over, are suggestive of a possible adverse effect associated with residence in NPCSs, even if a role of other factors cannot be excluded, due to the adoption of an ecological study design. Future analytical studies are needed to clarify if EDs are a TC risk factor for individuals living in NPCSs.