Mesothelioma Risk Among Maritime Workers According to Job Title: Data From the Italian Mesothelioma Register (ReNaM).

The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.

Incidence of mesothelioma in young people and causal exposure to asbestos in the Italian national mesothelioma registry (ReNaM).

INTRODUCTION: The epidemiological surveillance of mesothelioma incidence is a crucial key for investigating the occupational and environmental sources of asbestos exposure. The median age at diagnosis is generally high, according to the long latency of the disease. The purposes of this study are to analyse the incidence of mesothelioma in young people and to evaluate the modalities of asbestos exposure. METHODS: Incident malignant mesothelioma (MM) cases in the period 1993-2018 were retrieved from Italian national mesothelioma registry and analysed for gender, incidence period, morphology and exposure. Age-standardised rates have been calculated and the multiple correspondence analysis has been performed. The association between age and asbestos exposure has been tested by χ2 test. RESULTS: From 1993 to 2018, 30 828 incident MM cases have been collected and 1278 (4.1%) presented diagnosis at early age (≤50 years). There is a substantial association between age at diagnosis and the type of asbestos exposure and a significantly lower frequency of cases with occupational exposure to asbestos (497 cases vs 701 expected) in young people has been documented. Paraoccupational and environmental exposure to asbestos have been found more frequent in young MM cases (85 and 93 observed cases vs 52 and 44 expected cases, respectively). CONCLUSIONS: Mesothelioma incidence surveillance at population level and the anamnestic individual research of asbestos exposure is a fundamental tool for monitoring asbestos exposure health effects, supporting the exposure risks prevention policies. Clusters of mesothelioma incident cases in young people are a significant signal of a potential non-occupational exposure to asbestos.

Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018.

OBJECTIVES: Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers. DESIGN: Case-control study. SETTING: Cases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. METHODS: We selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses. RESULTS: The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower. CONCLUSIONS: We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Mesothelioma Risk among Construction Workers According to Job Title: Data from the Italian Mesothelioma Register.

BACKGROUND: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title. METHODS: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer. RESULTS: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past. CONCLUSIONS: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.

Indoor Radon Concentration Levels in Healthcare Settings: The Results of an Environmental Monitoring in a Large Italian University Hospital.

The aim of the study is to determine the radon concentrations in the University Hospital of Bari, Apulia Region, Southern Italy. The monitoring took place from 2017 to 2018 for a total of 402 days and included 3492 premises. Radon environmental sampling was performed with passive dosimeters of the CR-39 type. The highest mean concentration was found in basement rooms (118.9 Bq/m3), followed by ground-floor rooms (88.2 Bq/m3), first-floor rooms (78.1 Bq/m3), second-floor rooms (66.7 Bq/m3), and third-floor rooms (68.9 Bq/m3). An average radon concentration lower than the WHO recommended level of 100 Bq/m3 was detected in 73.5% of monitored environments, while only 0.9% exceeded the reference level of 300 Bq/m3 set by the national law (Legislative Decree 101/2020). The frequency of environments in which radon concentrations exceed 300 Bq/m3 is significantly higher in the basement (p-value < 0.001). As for a previous preliminary investigation in the same hospital conducted on a much smaller number of premises (n = 401), most of the monitored environments had radon concentrations lower than the reference levels set by the new national law, and the risk to the healthcare workers' health derived from occupational exposure to radon could be considered acceptable.

Case report: Mesothelioma and BAP1 tumor predisposition syndrome: Implications for public health.

BRCA-1 associated protein 1 (BAP1) tumour predisposition syndrome (TPDS) is a hereditary condition characterised by germline mutation of the tumour suppressor BAP1. This disorder is associated with the development of various benign and malignant tumours, mainly involving the skin, eyes, kidneys, and mesothelium. In this article, we report the case of a man recruited through the Apulia (Southern Italy) Mesothelioma Regional Operational Centre of the National Register of Mesotheliomas, who suffered from uveal melanoma, renal cancer, and mesothelioma, and a familial cluster of BAP1 germline mutations demonstrated by molecular analyses. The family members of the proband developed multiple malignancies. As tumours arising in this context have specific peculiarities in terms of clinical behaviour, identification of this condition through appropriate genetic counselling should be considered for adequate primary, secondary, and tertiary prevention measures for offspring.

Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).

BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates. OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship. METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42). CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.

Comparison of Three Different Waves in Healthcare Workers during the COVID-19 Pandemic: A Retrospective Observational Study in an Italian University Hospital.

Background: SARS-CoV-2 has infected many healthcare workers and (HCWs) worldwide. The aim of this study was to determine, analyze, and compare the frequency and characteristics of COVID-19 cases among HCWs of the University Hospital of Bari. Methods: A retrospective observational study was conducted after preventive protocol implementation. The SARS-CoV-2 infection frequency was determined by real-time reverse transcription-polymerase chain reaction on nasopharyngeal samples. Results: Overall, 519 HCWs (9%) tested positive among a total of 6030 HCWs during the three waves. The highest frequency of COVID-19 cases (n = 326; 63%) was observed during the 2nd wave, from September 2020 to December 2020, and the lowest (n = 34; 7%) was observed during the 1st wave, from March 2020 to August 2020 (p < 0.001). Working in a designated COVID-19 department was not a risk factor for infection. Conclusions: The correct use of personal protective equipment and the early identification of symptomatic workers are still essential factors to avoid nosocomial clusters, even in this current phase of vaccine availability.

Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.

There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.

Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.

Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.

The impact of COVID-19 on new mesothelioma diagnoses in Italy.

BACKGROUND: The aim of this work was to evaluate the impact of the restrictions put in place to control the COVID-19 pandemic on new diagnoses of malignant mesothelioma (MM) in Italy. METHODS: Twelve of the 21 Italian malignant mesothelioma CORs (regional operating centres) participated. The study included all cases of MM with microscopic confirmation; cases without microscopic confirmation and death certificate only (DCO) were excluded. For each case, information on sex, date of birth, tumor site, morphology, and date of diagnosis was retrieved. We compared the number of incident cases in 2020 with 2019, looking at the overall picture and for four periods: pre-pandemic (January-February), first wave (March-May), low incidence (June-September), and second wave (October-December). RESULTS: A total of 604 cases were registered: 307 in 2019 and 297 in 2020. In the 2020 pre-pandemic period, the incidence was higher than in the same months in 2019 (+45%); there was no significant change during the first wave (+1%) or in the low-incidence period (-3%), while a decrease was observed during the second wave (-32%). However, the data were not homogeneous across the country: the increase in the pre-pandemic period concerned mostly the regions of northern (+61.5%) and central Italy (+43.5%); during the first wave, MM diagnoses increased in the northern (+38.5%) and central (+11.4%) regions but decreased in the southern regions (-52.9%). All these differences are compatible with random fluctuations. CONCLUSION: The COVID-19 pandemic had little or no impact on new MM diagnoses, and variations were not homogeneous throughout the country.

Association between Long COVID and Overweight/Obesity.

BACKGROUND: Long COVID is a syndrome characterized by the persistence of SARS-CoV-2 infection symptoms. Among HCWs, prolonged COVID symptoms could lead to the inability to perform work tasks. The aim of this study is to investigate 35-day long-COVID (35-LC) characteristics and risk factors in a one-year period. METHODS: We carried out a retrospective cohort study during the COVID-19 pandemic at University Hospital of Bari. A total of 5750 HCWs were tested for close contact with a confirmed case, in the absence of personal protective equipment, or for symptom development. RESULTS: Each positive HCW was investigated for cardiovascular risk factors or respiratory diseases. An amount of 352 HCWs (6.1%) were infected by SARS-CoV-2, and 168 cases evolved to long COVID. The 35-LC group showed mean BMI values higher than the non-35-LC group (25.9 kg/m2 vs. 24.8 kg/m2, respectively), and this difference was significant (p-value: 0.020). Moreover, HCWs who suffered from pulmonary disease (OR = 3.7, CL 95%: 1.35-10.53; p-value = 0.007) or overweight (OR = 1.6 CL 95%: 1.05-2.56; p-value = 0.029) had an increased risk of developing 35-LC. CONCLUSIONS: Long COVID is an emerging problem for hospital managers as it may reduce the number of HCWs deployed in the fight against COVID-19. High BMI and previous pulmonary disease could be risk factors for 35-LC development in exposed HCWs.

Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report.

INTRODUCTION: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with poor survival that shares some similarities with the best-known pleural variant, pleural mesothelioma. The recent European Reference Network on Rare Adult Cancers (EURACAN)/International Association for the Study of Lung Cancer (IASLC) proposals attempted to improve the histological diagnosis and patient risk stratification. Herein, we investigated whether the pathology recommendations and suggestions of the pleural proposals were applicable to diffuse malignant peritoneal mesothelioma. METHODS: Fifty multiple laparoscopic biopsies of DMPM were consecutively collected at the Pathology Unit of the University of Bari. A two-tier system, i.e., low, and high grade, was used to categorize 34 epithelioid DMPMs. Architectural patterns, cytological features and stromal changes were also reported. Immunohistochemistry was performed for BRCA1-associated protein 1 (BAP1), programmed death-ligand 1 (PD-L1), and Ki67, while fluorescence in situ hybridization (FISH) was performed for p16/cyclin-dependent kinase inhibitor 2A (CDKN2A). RESULTS: High-grade epithelioid mesothelioma, high Ki67, and p16/CDKN2A deletion were significantly associated with short survival (p = 0.004, p < 0.0001, and p = 0.002, respectively). BAP1 loss and PD-L1 negativity were the most common findings. Multivariate analysis revealed that the nuclear grading system and p16 deletion significantly correlated with survival (p = 0.003 each). CONCLUSIONS: The present study examined the prognostic significance of several factors proposed for pleural mesothelioma in an extra pleural site. Notably, the introduction of a grading system may provide better risk stratification in epithelioid DMPM. Ki67, BAP1 and p16/CDKN2A should also be measured whenever possible. A detailed report with all supportive data would allow us to collect sufficient information for use in further studies on larger case series.

Legionnaires' disease arising with hirsutism: case report of an extremely confusing event.

BACKGROUND: Legionella bacteria is a common cause of pneumonia, but the infection may affect several organs in the most serious cases. A systemic involvement ab initio could be non-specific, leading to a diagnostic misinterpretation. CASE PRESENTATION: A 33-year-old woman had been complaining of mental confusion, restlessness, aggressiveness, and, subsequently, hirsutism. After 3 weeks, the patient developed pneumonia and died during the hospitalization. The autopsy examination revealed a multi-organ necrotizing exudative disease involving the lung, the heart and the brain. The microbiological tests of tracheal aspirate were positive for Legionella pneumophila serotype 1. CONCLUSION: The Legionella infection may show a proteiform clinical course and an extra-pulmonary manifestation may be the first sign of the disease. Herein, we report a case of Legionella infection in a young female, presenting with non-specific neurological symptoms and hirsutism at onset, misdiagnosed as a metabolic disease.

Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature.

Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors.

Silicosis in a paint-production worker: Study of a lung histological specimen with scanning electron microscopy-Energy dispersive X-ray spectrometer.

The occupational risks in silica-exposed workers have been greatly reduced over the last decades; however, only few studies investigated uncommon forms of exposure to crystalline silica as shown by this case of silicosis in a paint-production worker.

Large-scale IgM and IgG SARS-CoV-2 serological screening among healthcare workers with a low infection prevalence based on nasopharyngeal swab tests in an Italian university hospital: Perspectives for public health.

BACKGROUND: Healthcare workers (HCWs) are highly exposed to SARS-CoV-2 infection given their specific tasks. The IgG-IgM serological assay has demonstrated good accuracy in early detection in symptomatic patients, but its role in the diagnosis of asymptomatic patients is uncertain. The aim of our study was to assess IgM and IgG prevalence in sera in a large cohort of HCWs previously subjected to Nasopharyngeal swab test (NST) after accurate risk assessment due to positive COVID-19 patient exposure during an observation period of 90 days. METHODS: 2407 asymptomatic HCWs that had close contact with COVID-19 patients in the period between April 8th and June 7th were screened with NST based on the RT-PCR method. In parallel, they underwent large-scale chemiluminescence immunoassays involving IgM-IgG serological screening to determine actual viral spread in the same cohort. RESULTS: During the 90-day observation period, 18 workers (0.75%) resulted positive for SARS-CoV-2 infection at the NST, whereas the positivity rates for IgM and IgG were 11.51% and 2.37%, respectively (277 workers). Despite high specificity, serological tests were inadequate for detecting SARS-CoV-2 infection in patients with previous positive NST results (IgM and IgG sensitivities of 27.78% and 50.00%, respectively). CONCLUSIONS: These findings indicate a widespread low viral load of SARS-CoV-2 among hospital workers. However, serological screening showed very low sensitivity with respect to NST in identifying infected workers, and negative IgG and IgM results should not exclude the diagnosis of COVID-19. IgG-IgM chemiluminescence immunoassays could increase the diagnosis of COVID-19 only in association with NST, and this association is considered helpful for decision-making regarding returning to work.

Authors' response: Mezei et al's "Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis".

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, Brüning 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.

Asbestos Exposure and Malignant Mesothelioma in Construction Workers-Epidemiological Remarks by the Italian National Mesothelioma Registry (ReNaM).

Notwithstanding the ban in 1992, asbestos exposure for workers in the construction sector in Italy remains a concern. The purpose of this study is to describe the characteristics of malignant mesothelioma (MM) cases recorded by the Italian registry (ReNaM) among construction workers. Incident mesothelioma cases with a definite asbestos exposure have been analyzed. Characteristics of cases and territorial clusters of crude rates of MM in construction workers have been described, as well as the relation between asbestos use before the ban and the historical trend of workforce in the construction sector in Italy. ReNaM has collected 31,572 incident MM cases in the period from 1993 to 2018 and asbestos exposure has been assessed for 24,864 (78.2%) cases. An occupational exposure has been reported for 17,191 MM cases (69.1% of subjects with a definite asbestos exposure). Among them, 3574 had worked in the construction sector, with an increasing trend from 15.8% in the 1993-98 period to 23.9% in 2014-2018 and a ubiquitous territorial distribution. The large use of asbestos in construction sector before the ban makes probability of exposure for workers a real concern still today, particularly for those working in maintenance and removal of old buildings. There is a clear need to assess, inform, and prevent asbestos exposure in this sector.

COVID-19 hospital outbreaks: Protecting healthcare workers to protect frail patients. An Italian observational cohort study.

OBJECTIVES: To determine the prevalence of SARS-CoV-2 infection among exposed healthcare workers (HCWs) after preventive protocol implementation. METHODS: A total of 5750 HCWs were included in the study. Those in contact with COVID-19 patients were allocated into a high-risk or a low-risk group based on contact type (PPE- or non-PPE-protected); high-risk workers underwent nasopharyngeal swab tests, while among low-risk workers, swab tests were carried out only for symptomatic workers (active surveillance). The prevalence was determined by real-time reverse transcriptase-polymerase chain reaction on nasopharyngeal samples. RESULTS: 3570 HCWs had contact with 1065 COVID-19 patients. Among them, 3494 were subjected to active surveillance (low-risk group); 2886 (82.60%) were subjected to a swab test; and 15 were positive (0.52%). Seventy-six HCWs (2.13% of exposed) were included in the high-risk group, and a swab test was mandatory for each participant. Overall, 66 (86.84% of high-risk) were negative, and 10 were positive (13.16%), resulting in a higher risk of infection than in the low-risk group [OR = 29.00; 95% CI:12.56-66.94; p < 0.0001]. CONCLUSION: To date, the SARS-CoV-2 infection prevalence is 0.70% among exposed HCWs and 0.435% among all HCWs working at the examined university hospital. The correct use of PPE and the early identification of symptomatic workers are essential factors to avoiding nosocomial clusters.