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Objectives: The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods: Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993–2015, incidence rates, survival median period and prognostic factors have been evaluated. A case–control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results: Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85–7.31 and OR 3.42, 95% CI 1.93–6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions: For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.

Although the predominant occupation origin of mesothelioma is well known, determinant factors involved in filing compensation are scarcely investigated. A linkage between incident mesothelioma cases collected by Italian mesothelioma register (ReNaM) and compensation claims and assignment by Italian national insurance Institute (INAIL) has been conducted for cases diagnosed in the period 2010-2015 and occupational exposure to asbestos. Logistic regression models and decision tree models have been used to identify demographic, diagnostic and anamnestic factors significant for filing and receiving compensation. We have included in the analyses 5019 mesothelioma cases, and among them, 3321 (66.2 %) were found in INAIL archives as mesothelioma cases who fil claims for compensation. The modalities of asbestos exposure, sector of working activities and job type are crucial factors. Furthermore, gender, age at diagnosis, area of residence have been found to be significant predictors of probability to fil claims. Relative risks to fil claims were obtained for the above determinants and conditions to maximize the probability to obtain compensation identified. Our findings demonstrate that there is a need to enforce policies for improving awareness of the occupational origin for mesothelioma cases. Stakeholders, occupational health and safety institutions can play an important role for improving the sensitization regarding the rights of compensation benefits, ensuring the equity and the effectiveness of insurance, welfare and public health systems.

Objective To develop a short, flexible, and comprehensive tool to measure psychological distress in caregivers of malignant mesothelioma (MM) patients: the Mesothelioma Psychological Distress Tool-Caregivers version (MPDT-C). Methods Based on a systematic review of the relevant literature, aspects associated with caregiver distress were derived. Expert researchers/clinicians developed a pool of items for each identified aspect. Content validity was assessed through a multiple mixed-methods approach. A multicenter study was conducted to explore the factorial structure of the 47-item MPDT-C through Bayesian factor analysis. Results The Bayesian exploratory factor analysis revealed an underlying three-factor structure. Factors were labeled Secondary Traumatic Stress, Engagement in Caring, and Meaningful Cognitive Restructuring. All scales showed sufficient reliability and corrected item-total correlations. Females scored higher than males for Engagement in Caring. Conclusions Taking care of malignant mesothelioma patients is a stressful process that influences the caregiver's physical, emotional, and social wellbeing. Our study offers preliminary evidence in support of the adequate psychometric properties of the MPDT-C, and these should now be replicated. Results suggest that the MPDT-C is a reliable tool with which to detect the psychological distress of this traumatized population.

Objective Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer). Methods Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse. Results Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered. Conclusions Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance.

The aim of the study is to investigate exposures to vinyl chloride monomer (VCM) at workplace in Italy and the related burden of diseases. Measurements data was collected from a nation-wide occupational exposure registry (SIREP, 1996-2016). Potentially exposed workers were estimated for some industrial sectors. Concurrent exposures were investigated using cluster analysis. Proportionate mortality ratios were calculated linking data to national mortality statistics (2005-2015). Overall 8,460 measurements were analyzed. Most exposures occurred in the manufacture of chemicals and plastic products. A total of 12,148 workers potentially exposed was estimated (64% male). Concurrent exposures were detected frequently (83%). An elevated proportion of deaths for liver cancer was found in male exposed workers. Although VCM is a known carcinogen for humans, there are still many exposure situations, albeit at low doses, in the chemical and plastic industries.

Reconstruction of work history of subjects exposed to occupational carcinogens might be extremely challenging and provide unreliable results. This study, carried out in Italy from February to November 2014, aimed to explore the validity of an innovative approach to reconstruct the occupational history of workers who have previously been exposed to asbestos combining the administration of structured questionnaire with the use of administrative data. Subjects recruited in this study were enrolled in the cohorts of COSMOS 1 and 2 studies. Participants indicating an exposure to asbestos were contacted and a structured questionnaire was administered to them to verify the validity of the self-reported asbestos exposure. Subsequently, work histories of respondents were investigated using administrative information. The record linkage with social security archives allowed the reassembling of the complete work history of 487 participants. In detail, administrative files allow the retrieval of 98 % of workers declaring not to be exposed, versus 77 % using the questionnaire. Furthermore, the percentage of retrieved cases is not relevant for high risk sectors but it is almost double for industries with probable presence of asbestos. The combined and integrated use of structured questionnaire with administrative data proved effective in accurately identifying subjects who actually had an asbestos exposure. This innovative strategy, being cost-effective and easily adaptable to other carcinogens, could be particularly useful in selecting subjects to recruit in specific screening and control programs for the early diagnosis of occupational cancers.

Essentials The BCR-ABL negative myeloproliferative neoplasms are subjected to unknown phenotypic modifiers. GATA-1 is upregulated in ET patients, regardless of treatment regimen or mutational status. Myelofibrosis (MF) megakaryocytes displayed decreased GATA-1 staining. GATA-1 may have utility as a diagnostic marker in ET and in its differential diagnosis from MF. Abstract: Background The BCR-ABL-negative myeloproliferative neoplasms, i.e., polycythemia vera, essential thrombocythemia (ET), and myelofibrosis (MF), are characterized by mutations in JAK2, CALR, or MPL. However, an as yet unknown factor drives the precise disease phenotype. The hematopoietic transcription factor GATA-1 and its downstream targets NFE2 and FLI1 are responsible for determining erythroid and megakaryocyte lineages during hematopoietic stem cell differentiation. Previous studies have demonstrated a low level of GATA-1 expression in megakaryocytes from patients with MF. Objectives and methods The expression of GATA-1, NFE2 and FLI1 was studied for changes in the peripheral blood (PB) of ET patients. Peripheral blood samples were obtained from 36 ET patients, 14 MF patients, and seven healthy control donors. Total RNA from PB mononuclear cells (PBMCs) was extracted, and quantitative polymerase chain reaction was used to determine relative changes in gene expression. Protein levels of GATA-1 were also determined in bone marrow sections from ET and MF patients. Results GATA-1 mRNA was upregulated in ET patients, regardless of treatment regimen or mutational status. FLI1 expression was significantly downregulated, whereas NFE2 expression was unaffected by changes in GATA-1 mRNA levels. Megakaryocytes from ET patients showed increased protein levels of GATA-1 as compared with those from MF patients. Conclusions Our results confirmed, in PB, our previous data demonstrating elevated levels of GATA-1 mRNA in total bone marrow of ET patients. GATA-1 mRNA levels are independent of cytoreductive therapies, and may have utility as a diagnostic marker in ET and in its differential diagnosis from MF.

Aims We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy. Methods and results Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013–2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0–5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines. Conclusion PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.

IntroductionThe SARS-CoV-2 pandemic is an impacting challenge for occupational health. Epidemiological surveillance of COVID-19 includes systematic tracking and reporting of the total cases and deaths, but suitable experiences of surveillance systems for identifying the occupational risk factors involved in the COVID-19 pandemic are still missing, despite the interest for occupational safety and health.MethodsA methodological approach has been implemented in Italy to estimate the occupational risk of infection, classifying each economic sector as at low, medium-low, medium-high and high risk, based on three parameters: exposure probability, proximity index and aggregation factor. Furthermore, during the epidemic emergency, the Italian Workers’ Compensation Authority introduced the notation of COVID-19 work-related infection as an occupational injury and collected compensation claims of workers from the entire national territory.ResultsAccording to compensation claims applications, COVID-19 infection in Italy has been acquired at the workplace in a substantial portion of the total cases (19.4%). The distribution of the economic sectors involved is coherent with the activities classified at risk in the lockdown period. The economic sectors mostly involved were human health and social work activities, but occupational compensation claims also include cases in meat and poultry processing plants workers, store clerks, postal workers, pharmacists and cleaning workers.ConclusionsThere is a need to go towards an occupational surveillance system for COVID-19 cases, including an individual anamnestic analysis of the circumstances in which the infection is acquired, for the prevention of occupational infectious risk, supporting insurance system effectiveness and managing vaccination policies.

The aim of this study is to highlight tasks and jobs not commonly considered at high risk for sinonasal cancer (SNC) identified by Regional Operating Centers currently active in the Italian National Sinonasal Cancer Registry (ReNaTuNS), which retrieve occupational histories through a standardized questionnaire. Data on exposures to IARC carcinogenic agents in work settings unknown to be associated with SNC risk were collected and analyzed. Out of 2,208 SNC cases recorded in the ReNaTuNS database, 216 cases and their worked exposure periods were analyzed. Unsuspected jobs with exposure to wood dust include construction-related tasks, production of resins, agriculture and livestock jobs (straw and sawdust), and heel factory work (cork dust). Other examples are hairdressers, bakers (formaldehyde), dressmakers, technical assistants, wool and artificial fiber spinners, and upholsterers (textile dusts). Moreover, settings with coexposure to different agents (e.g., wood with leather dusts and chromium–nickel compounds) were recognized. The study describes jobs where the existence of carcinogenic agents associated with SNC risk is unexpected or not resulting among primary materials employed. The systematic epidemiological surveillance of all epithelial SNC cases with a detailed collection of their work history, as performed by a dedicated population registry, is essential for detecting all potential occupational cases and should be considered in the context of forensic medicine and the compensation process.

Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010–2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10–25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.

Mezei et al's letter (1) is an opportunity to provide more details about our study on pericardial and tunica vaginalis testis (TVT) mesothelioma (2), which is based on the Italian national mesothelioma registry (ReNaM): a surveillance system on mesothelioma, with individual asbestos exposure assessment. Incidence of pericardial mesothelioma has been estimated around 0.5 and 0.2 cases per 10 million person-years in men and women, respectively, and around 1 case for TVT mesothelioma. ReNaM collected 138 cases thanks to its long period of observation (1993-2015) and national coverage. Conducting a population-based case-control study with incidence-density sampling of controls across Italy and over a 23 year time-span should have been planned in 1993 and would have been beyond feasibility and ReNaM scope. We rather exploited two existing series of controls (3). The resulting incomplete time- and spatial matching of cases and controls is a limitation of our study and has been acknowledged in our article. The analysis of case-control studies can nevertheless be accomplished in logistic models accounting for the variables of interest, in both individually and frequency matched studies (4). Furthermore, analyses restricted to (i) regions with enrolled controls, (ii) cases with definite diagnosis, (iii) incidence period 2000-2015, and (iv) subjects born before 1950 have been provided in the manuscript, confirming the strength of the association with asbestos exposure (supplemental material tables S4-7). Following Mezei et al's suggestion, we performed further sensitivity analyses by restriction to regions with controls and fitting conditional regression models using risk-sets made of combinations of age and year of birth categories (5-year classes for both). We confirmed positive associations with occupational exposure to asbestos of pericardial mesothelioma, with odds ratios (OR) (adjusted for region) of 9.16 among women [95% confidence interval (CI) 0.56-150] and 5.63 (95% CI 1.02-31.0) among men; for TVT mesothelioma the OR was 7.70 (95% CI 2.89-20.5). Using risk sets of age categories and introducing year of birth (5-year categories) as a covariate (dummy variables) the OR were similar: OR (adjusted for region) of 9.17 among women (95% CI 0.56-150) and 5.76 (95% CI 1.07-31.0) among men; for TVT the OR was 9.86 (95% CI 3.46-28.1). Possible bias from incomplete geographical overlap between cases and controls has been addressed in the paper (table S4) and above. In spatially restricted analyses, OR were larger than in those including cases from the whole country, indicating that bias was towards the null. Mezei et al further noted that "the regional distribution of controls is different from that of person-time observed". This objection is not relevant because the above analyses were adjusted by region. Our controls were provided by a population-based study on pleural mesothelioma (called MISEM) and a hospital-based study on cholangiocarcinoma (called CARA). In MISEM, the response rate was 48.4%, a low but not unexpected rate as participation among population controls is usually lower and has been declining over time (5). It is important to underline that ReNaM applied the same questionnaire that was used for interviews and carried out the same exposure assessment as both MISEM and CARA. As repeatedly stated in ReNaM papers (6-7), each regional operating center assesses asbestos exposure based on the individual questionnaire, other available information, and knowledge of local industries. Occupational exposure to asbestos is classified as definite, probable or possible. Occupational exposure is (i) definite when the subject`s work was reported or otherwise known to have involved the use of asbestos or asbestos-containing materials (MCA); (ii) probable when subjects worked in factories where asbestos or MCA were used, but their personal exposure could not be documented; and (iii) possible when they were employed in industrial activities known to entail the use of asbestos or MCA. Hence, the definite and probable categories are closer to one another and were combined in our analyses. In any case, restricting analyses to subjects with definite occupational exposure and using each set of controls separately, as suggested by Mezei et al, yielded elevated OR for TVT and pericardial mesothelioma among men using both the above described modelling strategies; the OR could not be calculated for women. There were 70 (25 pericardial and 45 TVT) occupationally exposed mesothelioma cases. In population-based studies, analyses by occupation are limited by the low prevalence of most specific jobs. As briefly reported in our paper, for purely descriptive purposes, the industrial activity of exposure (cases may have multiple exposures), were construction (22 exposures, 7 and 15 for pericardial and TVT mesotheliomas, respectively), steel mills and other metal working industries (4 and 11), textile industries (2 and 3), and agriculture (2 and 5); other sectors had lower exposure frequencies. The absence of industries like asbestos-cement production, shipbuilding and railway carriages production/repair should not be surprising and had already been observed (7). In the Italian multicenter cohort study of asbestos workers (8), given the person-years of observation accrued by workers employed in these industries and gender- and site-specific crude incidence rates, approximately 0.1 case of pericardial and 0.2 of TVT mesothelioma would have been expected from 1970 to 2010. Even increasing ten-fold such figures to account for higher occupational risks among these workers would not change much. Asbestos exposure in agriculture has been repeatedly discussed in ReNaM reports (9: pages 70, 73, 128, 164 and 205). Exposure opportunities included the presence of asbestos in wine production, reuse of hessian bags previously containing asbestos, or construction and maintenance of rural buildings. Similarly, mesothelioma cases and agricultural workers exposed to asbestos have been noted in France (10). In conclusion, the additional analyses we performed according to Mezei et al's suggestions confirm the association between asbestos exposure and pericardial and TVT mesothelioma, supporting the causal role of asbestos for all mesotheliomas. ReNaM`s continuing surveillance system with national coverage is a precious platform for launching analytical studies on pleural and extra pleural mesothelioma. References 1. Mezei G, Chang ET, Mowat FS, Moolgavkar SH. Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis Scand J Work Environ Health. 2021;47(1):85-86. https://doi.org/10.5271/3909 2. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 3. Greenland S. Control-initiated case-control studies. Int J Epidemiol 1985 Mar;14(1):130-4. https://doi.org/10.1093/ije/14.1.130. 4. Pearce N. Analysis of matched case-control studies. BMJ 2016 Feb;352:i969. https://doi.org/10.1136/bmj.i969. 5. Bigert C, Gustavsson P, Straif K, Pesch B, Bruning T, Kendzia B et al. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015 Feb;57(2):202-9. https://doi.org/10.1097/JOM.0000000000000337. 6. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 7. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 8. Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L et al.; the working group. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure. Occup Environ Med 2017 Dec;74(12):887-98. https://doi.org/10.1136/oemed-2016-104100. 9. ReNaM VI Report. Available from: https://www.inail.it/cs/internet/docs/alg-pubbl-registro-nazionale-mesoteliomi-6-rapporto.pdf. Italian 10. Marant Micallef C, Shield KD, Vignat J, Baldi I, Charbotel B, Fervers B et al. Cancers in France in 2015 attributable to occupational exposures. Int J Hyg Environ Health 2019 Jan;222(1):22-9. https://doi.org/10.1016/j.ijheh.2018.07.015.

Purpose: Myelofibrosis is characterized by bone marrow fibrosis, atypical megakaryocytes, splenomegaly, constitutional symptoms, thrombotic and hemorrhagic complications, and a risk of evolution to acute leukemia. The JAK kinase inhibitor ruxolitinib provides therapeutic benefit, but the effects are limited. The purpose of this study was to determine whether targeting AURKA, which has been shown to increase maturation of atypical megakaryocytes, has potential benefit for patients with myelofibrosis. Patients and Methods: Twenty-four patients with myelofibrosis were enrolled in a phase I study at three centers. The objective of the study was to evaluate the safety and preliminary efficacy of alisertib. Correlative studies involved assessment of the effect of alisertib on the megakaryocyte lineage, allele burden, and fibrosis. Results: In addition to being well tolerated, alisertib reduced splenomegaly and symptom burden in 29% and 32% of patients, respectively, despite not consistently reducing the degree of inflammatory cytokines. Moreover, alisertib normalized megakaryocytes and reduced fibrosis in 5 of 7 patients for whom sequential marrows were available. Alisertib also decreased the mutant allele burden in a subset of patients. Conclusions: Given the limitations of ruxolitinib, novel therapies are needed for myelofibrosis. In this study, alisertib provided clinical benefit and exhibited the expected on-target effect on the megakaryocyte lineage, resulting in normalization of these cells and reduced fibrosis in the majority of patients for which sequential marrows were available. Thus, AURKA inhibition should be further developed as a therapeutic option in myelofibrosis. See related commentary by Piszczatowski and Steidl, p. 4868

Background/aim The relationship between air pollution and respiratory morbidity has been widely addressed in urban and metropolitan areas but little is known about the effects in non-urban settings. Our aim was to assess the short-term effects of PM10 and PM2.5 on respiratory admissions in the whole country of Italy during 2006–2015. Methods We estimated daily PM concentrations at the municipality level using satellite data and spatiotemporal predictors. We collected daily counts of respiratory hospital admissions for each Italian municipality. We considered five different outcomes: all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), lower and upper respiratory tract infections (LRTI and URTI). Meta-analysis of province-specific estimates obtained by time-series models, adjusting for temperature, humidity and other confounders, was applied to extrapolate national estimates for each outcome. At last, we tested for effect modification by sex, age, period, and urbanization score. Analyses for PM2.5 were restricted to 2013–2015 cause the goodness of fit of exposure estimation. Results A total of 4,154,887 respiratory admission were registered during 2006–2015, of which 29% for LRTI, 12% for COPD, 6% for URTI, and 3% for asthma. Daily mean PM10 and PM2.5 concentrations over the study period were 23.3 and 17 μg/m3, respectively. For each 10 μg/m3 increases in PM10 and PM2.5 at lag 0–5 days, we found excess risks of total respiratory diseases equal to 1.20% (95% confidence intervals, 0.92, 1.49) and 1.22% (0.76, 1.68), respectively. The effects for the specific diseases were similar, with the strongest ones for asthma and COPD. Higher effects were found in the elderly and in less urbanized areas. Conclusions Short-term exposure to PM is harmful for the respiratory system throughout an entire country, especially in elderly patients. Strong effects can be found also in less urbanized areas.

The pandemic has been afflicting the planet for over a year and from the occupational point of view, healthcare workers have recorded a substantial increase in working hours. The use of personal protective equipment (PPE), necessary to keep safe from COVID-19 increases the chances of overheating, especially during the summer seasons which, due to climate change, are becoming increasingly warm and prolonged. A web survey was carried out in Italy within the WORKLIMATE project during the summer and early autumn 2020. Analysis of variance (ANOVA) was used to evaluate differences between groups. 191 questionnaires were collected (hospital doctor 38.2%, nurses 33.5%, other healthcare professionals 28.3%). The impact of PPE on the thermal stress perception declared by the interviewees was very high on the body areas directly covered by these devices (78% of workers). Workers who used masks for more than 4 h per day perceived PPE as more uncomfortable (p &lt, 0.001) compared to the others and reported a greater productivity loss (p &lt, 0.001). Furthermore, the study highlighted a high perception of thermal stress among healthcare workers that worn COVID-19-PPE and this enhances the need for appropriate heat health warning systems and response measures addressed to the occupational sector.

Objectives This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres. Methods Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied. Results Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446–563; females 1027, 95% CI: 771–1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75–80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos. Conclusions Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.

Lung cancer (LC) mortality remains a consistent part of the total deaths occurring worldwide. Its etiology is complex as it involves multifactorial components. This work aims in providing an epidemiological assessment on occupational and environmental factors associated to LC risk by means of an ecological study involving the 8092 Italian municipalities for the period 2006–2015. We consider mortality data from mesothelioma as proxy of asbestos exposure, as well as PM2.5 and radon levels as a proxy of environmental origin. The compensated cases for occupational respiratory diseases, urbanization and deprivation were included as predictors. We used a negative binomial distribution for the response, with analysis stratified by gender. We estimated that asbestos is responsible for about 1.1% (95% CI: 0.8, 1.4) and 0.5% (95% CI: 0.2, 0.8) of LC mortality in males and females, respectively. The corresponding figures are 14.0% (95% CI: 12.5, 15.7) and 16.3% (95% CI: 16.2, 16.3) for PM2.5 exposure, and 3.9% (95% CI: 3.5, 4.2) and 1.6% (95% CI: 1.4, 1.7) for radon exposure. The assessment of determinants contribution to observed LC deaths is crucial for improving awareness of its origin, leading to increase the equity of the welfare system.

Introduction Telehealth (TH) services rapidly expanded during the COVID-19 pandemic. This rapid deployment precluded the opportunity for initial planning of implementation strategies. The purpose of the quality improvement project was to understand the needs of nurse practitioners and examine TH procedures and interventions designed to promote high-quality, equitable health care for pediatric patients with gastrointestinal concerns. Method The Plan-Do-Study-Act model was used. Survey data from providers and families were collected and analyzed. They were further illuminated through iterative dialog across the research team to determine the quality and efficiency of TH. Results A toolkit of strategies for promoting the quality and efficiency of TH was created according to the three domains of health equity: availability, accessibility, and acceptability. Discussion TH will be used in the postpandemic era. Institutions need to implement evidence-based strategies that ensure health equity across TH platforms to ensure excellent patient care.

COVID 19 is a major planetary emergency and intense workloads and the potential heat stress create critical conditions for healthcare workers. A web survey was carried out in Italy during summer 2020 as part of WORKLIMATE project with the aim of assessing the interaction between Personal Protective Equipment (PPE) and heat stress in healthcare workers. Preliminary results on 191 questionnaires show an increase of heat stress perception in the areas covered by PPE determining symptoms such as thirst, sweating and general distress. This information could be useful to allow preventive measure to safeguard health and productivity of these workers.

Introduction Histological studies reported that the His bundle (HB) is partitioned into narrow cords by collagen running in its long axis, providing the anatomical setting necessary for its longitudinal dissociation. Further confirmations came from the demonstration that direct HB pacing normalizes the QRS axis and duration in subjects with proximal HB lesions causing bundle branch block. However, there is no evidence of the possibility of selective HB partitions pacing destined to the composition of branches and fascicles. Methods and results We describe a case of intra-Hisian left bundle branch block in which permanent distal HB pacing corrects left ventricular delay and produces different QRS morphology at different voltage outputs, as an expression of different selective HB compartments recruitment. Conclusion This case would strengthen the limited data in the literature about HB longitudinal dissociation.

Despite their differences, pleural and peritoneal mesothelioma are frequently lumped together to describe epidemic curves and to forecast future mesothelioma trends. This study aims to describe the malignant peritoneal mesothelioma (MPeM) epidemic in Italy (1996–2016) and to forecast future trends up to 2040 in order to contribute to the assessment of MPeM future burden. All MPeM deaths in Italy from 1996–2016 were collected (as provided by the Italian National Statistical Institute (ISTAT)) in order to estimate MPeM mortality rates for each 3-year period from 1996 to 2016. Poisson age-period-cohort (APC) models were then used to forecast MPeM future trends. Between 2017 and 2040, 1333 MPeM deaths are expected. The number of MPeM deaths, as well as mortality rates, are expected to constantly decrease throughout the considered period. Based on considering the information from this study, it can be concluded that the MPeM epidemic has probably already reached its peak in Italy.

Background Remote control/monitoring (RC/M) of cardiac implantable electronic devices (CIEDs) is still underutilized, with a significant heterogeneity of use across and within countries. Not all models are equivalent in terms of effectiveness and efficiency. Purpose This cost comparative study aimed to analyse different models of following patients with CIEDs in three districts (four implanting facilities) merged into the same administrative area, to assess the impact of RC/M on expenditure, and to propose a common practice with the objectives of standardisation of approach, optimisation of efficiency, and future capillary implementation of RC/M. Methods The workload related to CIED-patient follow-ups was assessed in four public hospitals reflecting three different models with different proportions of patients followed by RC/M and different modus operandi. All CIED-patients in charge were scrutinized at 31/08/2019. The workload analysis was based on one-year data, collected retrospectively. Costs were calculated in terms of nursing and physician hours and based on public tariffs. Five variables, identified as drivers of costs, were tested by the simulation model. The main outcome was a total expenditure and cost per patient followed by RC/M compared to the standard care (SC) (in-office only). Results A total of 6830 patients with CIEDs were followed, 34.8% by RC/M (five platforms, 19.7% high voltage devices). An additional 25.8% had monitorable devices. The proportion of RC/M-patients across centres was 63.3%, 60.6%, 51% and 2.65%. RC/M resulted more costly than SC in all hospitals. Modelling demonstrated the overall cost in the year 2018 to be €228,075. No single factor optimisation tested separately (number of transmissions, nursing time for each transmission revision, doctor time for transmission processing, nursing time for phone calls, time for single enrolment) was able to reduce the cost per patient below the cost of SC. Providing monitoring to all compatible patients increased the costs of total care to €248,785. After the optimisation of other factors, the additional benefit of extending RC/M to compatible devices was achieved, with the final result of a total expenditure of €128,181 and of €15.97 per RC/M-patient per year vs. €27.93 per SC-patient, below the reimbursement tariff of monitoring recently approved in Veneto (€25.55 per patient/year). Conclusion Real-world data from an unselected population confirmed the huge inconsistency in managing patients with CIEDs. RC/M was associated with a significant specific workload. RC/M may be cost-saving compared to the standard in-office follow-up; however, organisation needs to be optimised. Improvement can be achieved by implementing new standards for RC/M procedures using Lean Management tools. A common platform might be of help. Centralisation could represent a further step to ensure high quality service and to save money at the same time. Funding Acknowledgement Type of funding source: None

Background Asbestos is a well-known carcinogen for humans. The aim of this study is to develop a tool to estimate occupational asbestos exposure in Italy after the ban using information collected in a national dataset. Methods Data were collected from firm registries of workers exposed to asbestos in the period 1996–2016. Descriptive statistics (arithmetic mean, standard deviation, geometric mean and geometric standard deviation) were calculated for the main exposure-related variables (activity sector, occupational group and exposure period). An estimate of workers potentially exposed to asbestos was also performed. Results A total of 19 704 airborne measurements of asbestos exposure was selected from the national database of occupational exposures in the sectors of asbestos abatement. Overall, a geometric mean of 7.93 f l−1 was found, and chrysotile was the asbestos type that had more exposures (41%). A total of 46 422 workers was estimated to be potentially at asbestos exposure risk. Exposure data were summarized by calendar period, activity sector and occupational group. Conclusions The construction of a job exposure matrix for different occupation/industry combinations may allow the assessment of occupational exposure to asbestos in several removal and disposal activities, and the estimate of the risks associated with asbestos-related diseases in epidemiological studies.

Background: Patients of malignant mesothelioma (MM) and their caregivers face significant physical and psychological challenges. The purpose of the present study is to examine the emotional impact after the diagnosis of MM in a group of patients and familial caregivers in a National Priority Contaminated Site (NPCS). Methods: A sample of 108 patients and 94 caregivers received a sociodemographic/clinical questionnaire, the Beck Depression Inventory II, the Davidson Trauma Scale, the Coping Orientation to the Problems Experienced&mdash, New Italian Version, and the Defense style questionnaire. The risk of depressive and post-traumatic stress disorder (PTSD) symptoms in relation to the strategies of coping and defense mechanisms was estimated in patients and caregivers separately by logistic regression models. Results: For patients, a high risk of depression was associated with high usage of Defense Style Questionnaire (DSQ) Isolation (OR: 53.33, 95% CI: 3.22&ndash, 882.30, p = 0.01) and DSQ Somatization (OR: 16.97, 95% CI: 1.04&ndash, 275.90, p = 0.05). Other significant risks emerged for some coping strategies and some defenses regarding both depression and trauma in patients and caregivers. Conclusions: This research suggests that for both patients and caregivers unconscious adaptive processes have a central role in dealing with overwhelming feelings related to the disease.

This case describes the feasibility of permanent His bundle pacing (HBP) with a standard bipolar lead positioned through cephalic access without a dedicated delivery sheath. The use of a stylet pre-shaped on an echocardiographic reference allowed a successful procedure without specific technical difficulties. This "simplified" approach may provide some advantages with respect to the only commercially available system.

Background The interatrial conduction time (IACT) is relevant for atrioventricular delay optimization in cardiac resynchronization therapy (CRT) devices. However, this information cannot be easily used as it requires invasive measurements. We tested whether electrical activation of left atrium (LA) could be detected in CRT devices with left ventricular (LV) sensing and used to estimate IACT. Methods The presence of LA activation on LV channel was evaluated in consecutive patients implanted with CRT and quadripolar LV leads whose sensing was temporarily set in the most proximal polarity (Ring LV4-housing). Estimates of IACT during sinus rhythm and atrial pacing were measured and compared with the values obtained with invasive catheterization of coronary sinus. Results Among six patients (50% female; mean age 73.3 ± 4.9 years) included in the analysis, four (66%) had a visible LA signal on the LV channel. The mean IACT measured with device electrograms was 71 ± 8 ms and 133 ± 15 ms during sinus rhythm and atrial pacing, respectively. These values were equivalent to the measurements obtained during invasive catheterization. Both patients without evidence of LA activation had an LV lead with a short total interelectrodes distance (46 mm) resulting in a significant anatomical distance between Ring LV4 and LA. Conclusions In CRT devices with left ventricular sensing, LA signal could be detected and used to estimate IACT especially if long-spaced electrodes are used.

Background The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people. Methods Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines. Results We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects. Conclusions This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties.

IntroductionThe epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.MethodsIncident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.ResultsIn the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.ConclusionsThe consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.

Background Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. Methods The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. Results Mortality was significantly increased for ‘All Causes’ and ‘All Malignant Neoplasm (MN)’, in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. Conclusions Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies. Electronic supplementary material The online version of this article (10.1186/s12940-019-0510-6) contains supplementary material, which is available to authorized users.

The technologically interesting properties of palladium nanoparticles (Pd-NPs) allowed their widespread industrial application, although concerns emerged on increasing general and occupational levels of exposure. In this context, to assess the toxicological behavior of Pd-NPs, and particularly their endocrine disruptive potential, has become a public health priority. Therefore, we evaluated Pd-NP impact on the female endocrine reproductive system of Wistar rats sub-chronically treated for 90 days with increasing doses of this xenobiotic (0.12, 1.2, and 12 µg/kg, administered at days 1, 30, and 60 for cumulative doses of 0.36, 3.6, and 36 µg/kg) via the intravenous route. In this regard, we investigated potential alterations in different sex hormone, for example, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone, progesterone, and testosterone, serum concentrations. All treated groups showed significantly greater levels of FSH compared to controls, suggesting a possible impact of Pd-NPs on the regulatory system that controls the normal physiology of female reproductive function. Although relevant, since obtained under sub-chronic, low-dose conditions of exposure resembling those encountered in real-world scenarios, the present results are preliminary and require confirmation as well as identification of the possible underlining molecular mechanisms. From a public and occupational health perspective, implications for the reproductive health of exposed subjects and the next generations of women exposed during their childbearing age or pregnancy should be elucidated. This information is essential to elaborate adequate preventive strategies for assessing and controlling possible Pd-NPs adverse effects on the endocrine system.

ObjectivesModels based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.MethodsWe used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.ResultsRates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.ConclusionsRates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Personal cooling garments (PCGs) can represent an adaptation solution to counteract heat strain and to improve worker's health and productivity (especially for some outdoor work activities as in agriculture and in the construction industry). The cooling effect of a ventilation jacket was preliminarily investigated carrying out “dry” tests in a climatic chamber on a thermal manikin. A standardized condition with air temperature, ta = 22.4 °C, three different adjustments of the fan velocity ( v f = 0, v f = 2 and v f = 4), and three different ensembles (the single jacket, a work ensemble and a combination of both) were considered. Results showed significant increases in dry heat losses (through convection) for the trunk thermal zones, higher when the fans were on, for all the ensembles considered. Percent changes greatly exceeded 100 % for the thermal zones close to the fans. The air ventilation determined significant decreases of the total thermal insulation ( I T ) values (up to 35 %) compared to the fans-off condition, confirming and quantifying the cooling effect of the ventilation jacket.

Outdoor workers are particularly exposed to climate conditions, and in particular, the increase of environmental temperature directly affects their health and productivity. For these reasons, in recent years, heat-health warning systems have been developed for workers generally using heat stress indicators obtained by the combination of meteorological parameters to describe the thermal stress induced by the outdoor environment on the human body. There are several studies on the verification of the parameters predicted by meteorological models, but very few relating to the validation of heat stress indicators. This study aims to verify the performance of two limited area models, with different spatial resolution, potentially applicable in the occupational heat health warning system developed within the WORKLIMATE project for the Italian territory. A comparison between the Wet Bulb Globe Temperature predicted by the models and that obtained by data from 28 weather stations was carried out over about three summer seasons in different daily time slots, using the most common skill of performance. The two meteorological models were overall comparable for much of the Italian explored territory, while major limits have emerged in areas with complex topography. This study demonstrated the applicability of limited area models in occupational heat health warning systems.

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc.

Since its introduction right ventricular apical (RVA) pacing has been the mainstay in cardiac pacing. However, in recent years there has been an upsurge of interest in permanent His bundle pacing (HBP), given the scientific evidence of the harmful role of dyssynchronous ventricular activation, induced by RVA pacing, in promoting the onset of heart failure and atrial fibrillation. After an intermediate period in which attention was focused on algorithms aimed at minimizing ventricular pacing, with partially inadequate and harmful results, scientific attention shifted to HBP, which proved to ensure a physiological electro-mechanical activation of the ventricles. The encouraging results obtained have allowed the introduction of HBP in recent guidelines for cardiac pacing in patients with bradicardia and cardiac conduction delay. Recent studies have also demonstrated the potential of HBP in patients with left bundle branch block and heart failure. HBP is promising as an attractive way to achieve physiological stimulation in patients with an indication for cardiac resynchronization therapy (CRT). Comparative studies of HB-CRT and biventricular pacing have shown similar results in numerically modest cohorts, although HB-CRT has been shown to promote better ventricular electrical resynchronization as demonstrated by a greater QRS narrowing. A widespread use of this pacing tecnique also depends on improvements in technology, as well as further validation of effectiveness in large randomised clinical trials

Even if the epidemic of malignant pleural mesothelioma (MPM) is still far from being over worldwide, the health effects of regulations banning asbestos can be evaluated in the countries that implemented them early. Estimates of MPM future burden can be useful to inform and support the implementation of anti-asbestos health policies all around the world. With this aim we described the trends of MPM deaths in Italy (1970&ndash, 2014) and predicted the future number of cases in both sexes (2015&ndash, 2039), with consideration of the national asbestos ban that was issued in 1992. The Italian National Statistical Institute (ISTAT) provided MPM mortality figures. Cases ranging from 25 to 89 years of age were included in the analysis. For each five-year period from 1970 to 2014, mortality rates were calculated and age&ndash, period&ndash, cohort Poisson models were used to predict future burden of MPM cases until 2039. During the period 1970&ndash, 2014 a total number of 28,907 MPM deaths were observed. MPM deaths increased constantly over the study period, ranging from 1356 cases in 1970&ndash, 1974 to 5844 cases in 2010&ndash, 2014. The peak of MPM cases is expected to be reached in the period 2020&ndash, 2024 (about 7000 cases). The decrease will be slow: about 26,000 MPM cases are expected to occur in Italy during the next 20 years (2020&ndash, 2039). The MPM epidemic in Italy is far from being concluded despite the national ban implemented in 1992, and the peak is expected in 2020&ndash, 2024, in both sexes. Our results are consistent with international literature.

The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.

As a backup lead in right ventricle (RV) is often used in His-bundle pacing (HBP) implants, in sinus rhythm patients the His lead is connected to the left ventricular (LV) port of a CRT device. In current devices, the backup pacing will be delivered 100% of time due to cross-channel ventricular refractory periods. Beyond an impact on battery, unnecessary RV pacing could find excitable tissue and capture a portion of the myocardium tissue potentially reducing the benefits of physiological HBP as shown in this case report where the switch from biventricular to LV-only pacing improved acute and 2-month echocardiography parameters.

ObjectivesStudies on the effect of temperature on rates of work-related injuries (WRIs) are very recent, and are evolving in depth and scope. However, less is known about potential effects of air pollutants. Our objective was to analyse the association between WRI and NO2, PM10and air temperature in three major Italian cities, and to identify groups of workers more at risk in Italy.DesignTime-stratified case-crossover study.SettingsMilan, Turin, Rome, years 2001–2010.ParticipantsA total of 468 816 WRI occurred between 2001 and 2010 in Milan, Turin and Rome were extracted from the Italian national workers’ compensation authority database.Main outcomesAssociations between WRI and temperature, PM10, NO2, separately in the warm and in the cold season (WS, May–September; CS, November–February). Effect modification was studied by economic sector, occupational activity and indoor/outdoor job activity.ResultsExposure to NO2(lag 0–8) showed the highest effect on the risk of WRI,with ORs ranging from 1.20 (95% CI 1.16 to 1.24) in Milan to 1.30 (95% CI 1.24 to 1.37) in Turin in the WS. The effect of exposure to PM10was milder but consistent across all cities: ORs from 1.09 (95% CI 1.05 to 1.12) in Turin to 1.15 (95% CI 1.11 to 1.18) in Rome. Temperature was associated with risk of WRI only among those working in construction (highest association in Rome 1.06; 95% CI 1.01 to 1.12), transportation (highest association in Milan 1.05; 95% CI 0.96 to 1.14) and the energy industry (highest association in Milan 1.57; 95% CI 1.03 to 2.38) in the WS in all cities. A weak effect of low temperatures was observed in the CS only in Rome.ConclusionsExposures to NO2resulted as strongest hazard for WRIs, mainly in warm months, while the independent effect of temperature was significant only in specific subgroups of workers. These results could be considered to better plan safety prevention programmes.

Simple Summary Asbestos consumption figures could be used to construct epidemiological models to forecast the pleural mesothelioma mortality, although they are not frequently taken into consideration in this kind of analysis. Our purpose is to predict the future burden of pleural mesothelioma deaths in Italy until 2039 and to describe the exposure–response curve considering time lasted from the exposure start. Our results could be of interest to plan future needs of the Italian health system and to provide evidence on the consequences of asbestos exposures useful for countries in which this material is, at present, still used for productive activities. Abstract Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970–2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure–response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20–40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed.

5506 Background: Intensive follow-up in cancer patients, which absorbs a lot of health system resources and can be a source of increased stress for patients, are often proposed on the assumption that an early recognition of relapse will translate in better outcomes. In endometrial cancer few randomized controlled trials were conducted to assess the role of a reduced number of the scheduled visits and of different settings of the follow-up, but did not investigate the contribution of routine serum, cytological or imaging follow-up investigations in improving overall survival or quality of life. The TOTEM study was planned to compare an intensive (INT) vs minimalist (MIN) 5- year follow-up regimen in endometrial cancer patients in terms of overall survival (OS). Methods: Patients surgically treated for endometrial cancer, in complete clinical remission confirmed by imaging, FIGO stage I-IV, were stratified by center and in low (LoR) or high (HiR) risk of recurrence and then randomized to INT or MIN hospital-based follow-up regimens. The main study hypothesis was to demonstrate an improvement from 75% to 80% (expected hazard ratio, HR = 0.78) of the 5-year OS with the INT regimen. Secondary objectives were to compare relapse free survival (RFS), health-related quality of life (HRQL) assessed at baseline, at 6 and 12 months and then yearly (with the SF-12 Physical and Mental Health Summary Scale) and costs. Results: 1884 patients were randomized in 42 centers between 2008 and 2018, and 1847 patients were available for the final analysis (60% LoR). Compliance with the follow-up scheduled visits was 75.3%, similar between INT (74.7%) and MIN (75.9%) arms, whereas the mean number of recorded exams (laboratory or imaging) was markedly higher in the INT than in the MIN arms (9.7 vs 2.9, p < 0.0001). After a median follow-up of 66 months, the overall 5-year OS was 91.3%, 90.6% in the INT and 91.9% in the MIN arms, respectively (HR = 1.12, 95%CI 0.85-1.48, p = 0.429). Comparing the INT vs MIN arms, the 5-year OS were 94.1% and 96.8% (HR = 1.48, 0.92-2.37, p = 0.104) in the LoR and 85.3% and 84.7% (HR = 0.96, 0.68-1.36, p = 0.814) in the HiR group. No relevant differences emerged in RFS between INT and MIN regimens, (HR = 1.13, 0.87-1.48, p = 0.365). At the time of the relapse most women were asymptomatic (146/228, 64.0%), with a tendency of higher proportions in the INT than in the MIN arm, both in the LoR group (78.8% vs 61.1%, p = 0.070) and in the HiR one (64% vs 60%, p = 0.754). HRQL was available only for a subgroup of patients (50% at baseline) and did not differ between arms. Conclusions: Intensive follow-up in endometrial cancer treated patients showed a weak and uncertain advantage in detecting earlier asymptomatic relapses but did not improve OS, even in HiR patients, nor influenced HRQL. Frequent routine use of imaging and laboratory exams in these patients should be discouraged. Clinical trial information: NCT00916708.

Finkelstein1 invited physicians and researchers interested in mesothelioma to investigate on past usage of talcum powders by affected people. In Italy, asbestos contamination in talc for industrial use has been documented,2 and, as he underlines tremolite contamination at low levels of cosmetic and pharmaceutical talc has been reported in USA by Blount3 and Gordon and colleagues.4 In the Italian National Mesothelioma Register (ReNaM), the analysis of intensive exposure to talc has been evaluated with respect to occupational and environmental history. The catalogue of possible asbestos exposure circumstances (a tool for the interviewers) reports the potential presence of industrial talcs in quarries or mines working activities, in leather tanning and in rubber industries. The use of intensive cosmetic talc for personal use is evaluated by means of a structured questionnaire,5 as reported in the ReNaM guidelines (see https://www.inail.it/cs/internet/docs/all-linee-guida-renam.pdf%3Fsection=attivita, p82, p98, in Italian). In our paper regarding gender differences in mesothelioma epidemiology,6 we have presented figures referring to 21 463 MM cases detected by ReNaM with a diagnosis between 1993 and 2012. Among female case list (6087 cases), 4374 cases (71.9%) have been interviewed for defining exposure. During the interview, 30 MM female cases referred an intensive use of talc in the context of occupational or life habits. For five of them, the regional centre has identified an exposure to asbestos due to intensive talc use, classifying such modality of exposure as ‘leisure activities’ (see ReNaM guidelines5). For the remaining 25 cases, an occupational exposure to asbestos in other working (or familiar or environmental) circumstances has been identified and coded. Registry data such as those provided by ReNaM cannot provide estimates of the mesothelioma risk associated with any particular exposure circumstance. We plan to include talc exposure at work and cosmetic talc usage in the analyses of a case–control study on pleural mesothelioma currently under way. A specific survey to compare and discuss how the modalities of exposure to talc have been evaluated in patients with mesothelioma in countries where epidemiological surveillance systems are active could improve knowledge and support prevention policies.

Recently, palladium nanoparticles (PdNPs) have been increasingly used in many industrial sectors, and this has led to a significant release of nano-sized palladium particles into the environment. However, despite the increase in occupational and general population exposure, information on the potential adverse effects of these PdNPs is still limited and their impact on the immune system constitutes a major health concern. Therefore, the aim of this study was to investigate the potential adverse effects induced by subchronic intravenous administration of PdNPs on the immune system of female Wistar rats by evaluating alterations in Interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon (INF)-γ, and Tumor Necrosis Factor (TNF)-α serum levels. Exposed and control animals were randomly divided into five groups (0, 0.012, 0.12, 1.2, and 12 μg PdNPs per kg body weight) which were treated with repeated intravenous injections of vehicle or PdNPs (on day 1, 30, and 60). Subchronic exposure to PdNPs induced a decreasing trend in serum levels in most of the cytokines investigated, with the highest concentration (12 μg/kg) determining significant inhibitory effects. Overall, these results showed that PdNPs are able to alter cytokine serum levels in subchronically treated Wistar rats, suggesting a possible impact of these xenobiotics on the immune system after long-term exposures.

Background Brain metastases (BM) from epithelial ovarian cancer (EOC) are considered a rare and unfavourable event. There is no consensus regarding the best management of these patients. Methods A multicenter retrospective analysis of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of the MITO (Multicenter Italian Trials in Ovarian cancer) group was conducted. Univariate and multivariate analysis were performed. Results A total of 174 women were identified as having BM from EOC. The median time interval between primary diagnosis of EOC and occurrence of BM was 26months (range 2–129months). The median overall survival from primary EOC diagnosis was 48months (95% CI 39.5–56.4months) and from diagnosis of BM was 12months (95% CI 9.6–14.3months). The majority of enrolled women (81.7%) were classified as sensitive to platinum-based chemotherapy. Four variables were significantly associated with poor overall survival in multivariate analysis: multiple BM [HR: 1.86 (95% CI: 1.22–2.84)], presence of extracranial disease [HR: 1.77 (95% CI: 1.11–2.83)] age [HR: 1.74 (95% CI: 1.17–2.59)], and monotherapy [HR: 2.57 (95% CI: 1.64–3.86)]. On the contrary, residual tumor at primary surgery, FIGO stage at primary diagnosis and platinum sensitivity were found to have no significant impact on survival from diagnosis of brain lesions. Conclusions Our results suggest that BM is a rare and late manifestation of EOC, with a 12-month life-span expectation. Multiple approach is a positive independent prognostic factor and should be proposed to carefully selected patients.

Introduction: Fluoropyrimidines such as 5-fluorouracil (5-FU) and its orally active prodrug, capecitabine, are widely used in the treatment of gastrointestinal cancer, including colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) plays an important role in the 5-FU metabolism. Dihydropyrimidine dehydrogenase gene (DPYD) is a highly polymorphic gene with several hundreds of reported genetic variants and DPD activity levels vary considerably among individuals, with different 5-FU-related efficacy and toxicity. About 5% of the population is deficient in DPD enzyme activity. The most well studied DPYD variant is the IVS14+1G>A, also known as DPYD ∗2A. In this report, we present a case of a patient with a double heterozygote DPYD variant (DPYD activity score: 0,5 according to Clinical Pharmacogenetics Implementation Consortium) who experienced a severe fluoropyrimidine-related toxicity resolved without any consequence. Patient concerns: A 46-years-old Caucasian man with diagnosis of left colon adenocarcinoma underwent left hemicolectomy on July 2017: pT3 G3 N1c M0. According to the disease stage, he started an adjuvant therapy with XELOX using capecitabine at 50% of total dose, because of his DPYD IVS14+1G>A variant, detected before the treatment. DIAGNOSIS: After few days, despite of this dose reduction, he experienced life-threatening adverse events such as mucositis G3, diarrhea G3, neutropenia G4, thrombocytopenia G4, and hyperbilirubinemia G3 according to Common Terminology Criteria for Adverse Events v 5.0. Interventions: As first, we set up an intensive rehydration therapy, antibiotic and antifungal prophylaxis, Granulocyte-Colony Stimulating Factors, and supportive blood transfusions. Additional genetic tests revealed a double heterozygote variant of DPYD gene (DPYD IVS14+1G>A and 2846A>T) which is a very rare situation and only 3 cases are described in literature, all of them concluded with patient's death. Outcomes: After 3 weeks of intensive therapy, the patient was fully recovered. Furthermore, all the whole-body CT scans performed since discharge from the hospital until now, have confirmed no evidence of disease. Conclusions: Recent studies demonstrated that screening strategy for the most common DPYD variants allowed for avoiding toxicities and saving money. This report underlines the importance of genotyping DPYD before treatment and emphasizes the role of genotype-guided dose individualization.