Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. METHODS: Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March-April 2021. RESULTS: Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. CONCLUSIONS: Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented.

Immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers in Milan (Lombardy Region, Northern Italy).

OBJECTIVES: to evaluate immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers (HCWs). DESIGN: cohort study. SETTING AND PARTICIPANTS: in a hospital in Milan (Lombardy Region, Northern Italy) HCWs without ("negative cohort") and with ("positive cohort") history of SARS-CoV-2 infection or elevated serum antibody before the vaccination campaign (27.12.2020) were included. Data collection and follow-up covered the period 27.12.2020-13.05.2022. MAIN OUTCOMES MEASURES: 1. serum anti-spike-1 (anti-S1) antibody levels after vaccination; 2. vaccine effectiveness (VE) against SARS-CoV-2 infections (either symptomatic or not) in the negative cohort. Data on infections were extracted from multiple sources (laboratory, accident reports, questionnaires). Vaccination was treated as a time-dependent variable. Using unvaccinated person-time as reference, hazard ratios (HR) of infections and 95% confidence intervals (95%CI) were calculated with a Cox regression model adjusted for gender, age, and occupation. VE was calculated as (1 - HR)×100. RESULTS: 5,596 HCWs were included, 4,771 in the negative and 825 in the positive cohort. In both cohorts, serum anti-S1 antibodies were high one months after the second dose, halved after six months, and returned to high levels after the third dose. In the negative cohort, 1,401 SARS-CoV-2 infections were identified. VE was 70% (95%CI 54-80; 46 infected) in the first four months after the second dose and later declined to 16% (95%CI 0-43; 97 infected). After the third dose, VE increased to 57% (95%CI 35-71; 61 infected) in the first month but rapidly declined over time, particularly after three months (24% in the fourth month and 1% afterwards). The number of infections avoided by vaccination was estimated to be 643 (95%CI 236-1,237). CONCLUSIONS: in spite of rapidly declining effectiveness, vaccination helped to avoid several hundred infections in the considered hospital.

Loss of consciousness in a helicopter pilot as plausible first sign of insulinoma: a case report.

A 50-year-old man who worked as a helicopter rescue pilot transiently lost consciousness while piloting a helicopter rescue. In the diagnostic process, all tests for the main possible differential diagnoses of loss of consciousness (cardiological and neurological) were performed and yielded normal results. Blood chemistry tests revealed recurrent fasting hypoglycemia and Chromogranin A was at the upper limit of normal. Fine needle aspiration guided by endoscopic ultrasonography was used to diagnose insulinoma-type neuroendocrine tumor of the pancreas. According to the Italian policies, the occupational physician aims to maintain professional skills without neglecting flight safety. A careful analysis of the relationship between the characteristics of the state of health of the aviator and his specific work needs was carried out, and he was given the opportunity to continue working as a rescue pilot thanks to medical therapies associated with organizational interventions in the workplace.

Side effects among healthcare workers from a large Milan university hospital after second dose of BNT162b2 mRNA COVID-19 vaccine.

BACKGROUND: In Italy, healthcare workers (HCWs) were among the first to receive COVID-19 vaccination. Aim of the present study is to evaluate frequency and severity of adverse events (AEs) following the second dose of BNT162b2 vaccine among HCWs of a large university hospital in Milan, Italy. METHODS: One month after having received the second dose of vaccine, HCWs filled-in a form about type, severity, and duration of post-vaccination local and systemic symptoms. We calculated the overall frequency of AEs and used multivariable Poisson regression models (adjusted for sex, age, BMI, smoking, allergy history, previous SARS-CoV-2 infection, anti-hypertensive therapy, and occupation) to calculate risk ratios (RR) and 95% confidence intervals (CI) of AEs according to selected variables. RESULTS: We included 3659 HCWs. Overall, 2801 (76.6%) experienced at least one local event, with pain at injection site being the most frequent (2788, 76.2%). Systemic events were reported by 2080 (56.8%) HCWs, with fatigue (52.3%), muscle pain (42.2%), headache (37.7%), joint pain (31.9%), and fever (26.2%) being the most frequent. Risks of systemic events were associated with female gender (RR=1.14, CI: 1.06-1.23), age (strong decrease with increasing age, p-trend<0.001), allergy history (RR=1.13, CI: 1.05-1.20), and current smoking (RR=0.90, CI: 0.84-0.97). HCWs with previous SARS-CoV-2 infection (even if symptomatic) were not at increased risk. CONCLUSIONS: Both local and systemic acute effects after second dose of BNT162b2 vaccine were frequently reported. However, symptoms were mostly light/mild and of short duration. Thus, our findings support the safety of COVID-19 vaccination in adults in relatively good health.

Estimate of environmental and occupational components in the spatial distribution of malignant mesothelioma incidence in Lombardy (Italy).

INTRODUCTION: Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure. OBJECTIVE: Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure. MATERIALS AND METHODS: We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Mollié model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model. RESULTS: We globally analyzed 6226 MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region. CONCLUSION: The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.

Impact of an asbestos cement factory on mesothelioma incidence in a community in Italy.

BACKGROUND: Broni is a small town (9000 inhabitants) in the province of Pavia, Lombardy, north-west Italy, where the second largest Italian asbestos cement factory (Fibronit) was in operation between 1932 and 1993. Based on Lombardy Mesothelioma Registry (RML) data (2000-2011), we previously showed a high impact of asbestos exposure on malignant mesothelioma (MM) incidence among Fibronit workers, their families, and people living in Broni and in the nearby town of Stradella (11,000 residents). Given the great concern of the community, we have recently updated the data regarding 5 more years (2012-2016). METHODS: From the RML database we extracted subjects who ever worked in Fibronit, their family members, ever residents in Broni, and subjects living in Stradella and nearby towns at the time of diagnosis. For each type of exposure we calculated standardized incidence ratios (SIR = observed/expected cases). RESULTS: In the period 2000-2016 we registered 56 cases (2.52 expected, SIR = 22.2), 49 men (41 pleural, 8 peritoneal MM), 7 women (5 pleural, 2 peritoneal MM) with past occupational exposure in Fibronit. Among subjects never occupationally exposed and never exposed to extra-occupational sources unrelated to Fibronit, we counted 39 cases (4.24 expected, SIR = 9.2), 10 men (all pleural MM), 29 women (28 pleural, 1 peritoneal MM) in Fibronit workers' families, 91 pleural mesothelioma cases (7.43 expected, SIR = 12.2, 31 men, 60 women), ever residents in Broni, and 25 pleural mesothelioma cases (3.05 expected, SIR = 8.2, 6 men, 19 women) living in Stradella at the time of diagnosis. The overall number of excess cases was about 194 (211 against 17.24 expected). In the remaining adjacent (No. 8) and surrounding (No. 17) municipalities (32,000 people) there were 7 cases (1 men, 6 women, 8.85 expected). CONCLUSION: The mesothelioma burden related to the asbestos cement factory is still high on factory workers, their families, and residents in Broni and Stradella towns.

Occupational asthma and rhinitis due to wheat flour: sublingual specific immunotherapy treatment.

BACKGROUND: There are several potential sensitizers in the bakery environment and wheat flour appears to be the dominant sensitizer in most bakeries. Apart from traditional drug therapy or a change in profession, there are no effective therapies for workers who develop serious respiratory symptoms in the workplace. OBJECTIVES: To describe clinical and laboratory findings in workers with asthma and/or rhinitis induced by wheat flour who underwent sublingual specific immunotherapy (SLIT). METHODS: Since drug therapy and prevention strategies were not effective, five bakers were elected to undergo SLIT. A three-year study was led by administering a sublingual wheat flour extract. Questionnaires, allergy and respiratory tests were performed before and after SLIT. RESULTS: After SLIT an improvement in symptoms is observed in every patient: Asthma Control Test and a quality-of-life questionnaire show higher scores and as a result, workers have reduced the use of drug therapy. We observed significantly reduced exhaled nitric oxide (FeNO) and eosinophil cationic protein (ECP) levels after SLIT, hypothesizing that these parameters may be used to monitor the effectiveness of immunotherapy. The improvement of FEV1 (forced expiratory volume in 1second) and responsiveness to bronchoprovocative tests with methacholine denotes a possible role of SLIT in treating patients with low-respiratory tract involvement, even though more data are needed. DISCUSSIONS: This is the first report in the literature on the use of SLIT for baker's asthma and rhinitis. SLIT for occupational wheat flour allergy should be possible and efficient, saving vocational training, professionalism, and avoiding job loss.

Directional Relationship Between Vitamin D Status and Prediabetes: A New Approach from Artificial Neural Network in a Cohort of Workers with Overweight-Obesity.

Objective: Despite the increasing literature on the association of diabetes with inflammation, cardiovascular risk, and vitamin D (25(OH)D) concentrations, strong evidence on the direction of causality among these factors is still lacking. This gap could be addressed by means of artificial neural networks (ANN) analysis.Methods: Retrospective observational study was carried out by means of an innovative data mining analysis-known as auto-contractive map (AutoCM)-and semantic mapping followed by Activation and Competition System on data of workers referring to an occupational-health outpatient clinic. Parameters analyzed included weight, height, waist circumference, body mass index (BMI), percentage of fat mass, glucose, insulin, glycated hemoglobin (HbA1c), creatinine, total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, uric acid, fibrinogen, homocysteine, C-reactive protein (CRP), diastolic and systolic blood pressure, and 25(OH)D.Results: The study included 309 workers. Of these, 23.6% were overweight, 40.5% were classified into the first class of obesity, 23.3% were in the second class, and 12.6% were in the third class (BMI > 40 kg/m ). All mean biochemical values were in normal range, except for total cholesterol, low- and high-density lipoprotein cholesterol, CRP, and 25(OH)D. HbA1c was between 39 and 46 mmol/mol in 51.78%. 25(OH)D levels were sufficient in only 12.6%. Highest inverse correlation for hyperglycemia onset was with BMI and waist circumference, suggesting a protective role of 25(OH)D against their increase. AutoCM processing and the semantic map evidenced direct association of 25(OH)D with high link strength (0.99) to low CRP levels and low high-density lipoprotein cholesterol levels. Low 25(OH)D led to changes in glucose, which affected metabolic syndrome biomarkers, first of which was homeostatic model assessment index and blood glucose, but not 25(OH)D.Conclusions: The use of ANN suggests a key role of 25(OH)D respect to all considered metabolic parameters in the development of diabetes and evidences a causation between low 25(OH)D and high glucose concentrations.

Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.

OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy. METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education. RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency. CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.

Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.

BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions. METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP). RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively). CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.

Determinants of metabolic syndrome in obese workers: gender differences in perceived job-related stress and in psychological characteristics identified using artificial neural networks.

OBJECTIVE: The metabolic syndrome (MS) is a multifactorial disorder associated with a higher risk of developing cardiovascular diseases and type 2 diabetes. However, its pathophysiology and risk factors are still poorly understood. In this study, we investigated the associations among gender, psychosocial variables, job-related stress and the presence of MS in a cohort of obese Caucasian workers. METHODS: A total of 210 outpatients (142 women, 68 men) from an occupational medicine service was enrolled in the study. Age, BMI, waist circumference, fasting glucose, blood pressure, triglycerides and HDL cholesterol were collected to define MS. In addition, we evaluated eating behaviors, depressive symptoms, and work-related stress. Data analyses were performed with an artificial neural network algorithm called Auto Semantic Connectivity Map (AutoCM), using all available variables. RESULTS: MS was diagnosed in 54.4 and 33.1% of the men and women, respectively. AutoCM evidenced gender-specific clusters associated with the presence or absence of MS. Men with a moderate occupational physical activity, obesity, older age and higher levels of decision-making freedom at work were more likely to have a diagnosis of MS than women. Women with lower levels of decision-making freedom, and higher levels of psychological demands and social support at work had a lower incidence of MS but showed higher levels of binge eating and depressive symptomatology. CONCLUSION: We found a complex gender-related association between MS, psychosocial risk factors and occupational determinants. The use of these information in surveillance workplace programs might prevent the onset of MS and decrease the chance of negative long-term outcomes. LEVEL OF EVIDENCE: Level V, observational study.

25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs.

OBJECTIVE: In recent years, the welfare of workers and the prevention of chronic disabling diseases has become a topic of great interest. This study investigates serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight-obese and insulin-resistant northern Italian indoor workers in apparent good health followed a nutritional education program. METHODS: An observational cross-sectional study on 385 patients (females = 291, males = 94), age range 18-69 years and body mass index (BMI) > 25 kg/m2, was performed at the Department of Occupational Medicine Milan, Italy, latitude 45.465454 N. We evaluated nutritional intakes, occupational and leisure physical activity, anthropometric measurements, impedance evaluation, blood pressure, the presence of metabolic syndrome (MetS) and nonalcoholic fatty liver diseases (NAFLD) by fatty liver index (FLI). Hematologic and biochemical parameters and (25(OH)D) levels were evaluated from fasting blood samples. RESULTS: Only 10.91% of subjects had optimal values of 25(OH)D; 17.40% of the remaining 89.09% subjects were severely deficient, with no gender difference and insufficient intake of vitamin D. Only 28% declared leisure physical activity; 39.48% had metabolic syndrome and 62.60% had an FLI > 30. An inverse relationship between 25(OH)D levels and BMI was found, with a significant reduction of total 25(OH)D serum concentrations in winter. The homeostasis model assessment-insulin resistance (HOMA-IR) is positively related to BMI and inversely related to 25(OH)D concentrations. A positive correlation between vitamin D and leisure physical activity was found. At univariate analysis adjusted for age, gender and BMI, an inverse relationship between vitamin D and FLI was observed in both genders. The correlation between 25(OH)D levels, inflammation markers, BMI, and FLI showed an increased risk of cardiovascular disease in this cohort of workers. CONCLUSION: Our results suggest the rationale for a large-scale screening program for vitamin D by means of easily implementable low-cost preventive supplementation.

Pleural malignant mesothelioma in dental laboratory technicians: A case series.

Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.

Delphi consensus on the monitoring tools of main individual risk factors for chronic diseases by the company doctor. / Ricerca di consenso Delphi sugli strumenti per il monitoraggio da parte del medico competente dei principali fattori di rischio individuali per malattie croniche.

BACKGROUND: Data on individual risk factors for chronic diseases (smoking, physical activity, body mass) are collected by company physicians in heterogeneous ways. This makes comparisons, researches and evaluations difficult. OBJECTIVES: The aim of the study was to find a consensus on evaluation tools for chronic diseases risk factors and for health promotion programs in workplaces that could be performed by company physicians during their clinical activity. METHODS: A first set of tools, proposed by a working group of occupational physicians in Bergamo, was submitted through the Delphi technique to a national expert panel of 22 persons including recognized national experts in specific fields and occupational physicians skilled in health promotion. RESULTS: In three Delphi rounds, the panel selected a set of tools to monitor the main individual risk factors for chronic diseases (smoking, alcohol, physical activity, nutrition, stress and mental health) as well as general data related to the worker and his job. CONCLUSIONS: The use of these specific tools, collected in a homogeneous format, should be recommended to all Italian company physicians, in particular those who work in WHP-programs, in order to allow analysis, comparison and evaluation of health promotion programs effectiveness at a national level.

Incidence of mesothelioma in Lombardy, Italy: exposure to asbestos, time patterns and future projections.

OBJECTIVES: In Italy, asbestos has been extensively used from 1945 to 1992. We evaluated the impact of exposure to asbestos on occurrence of malignant mesothelioma (MM) in the Lombardy Region, Northwest Italy, the most populated and industrialised Italian region. METHODS: From the Lombardy Mesothelioma Registry, we selected all incident cases of MM diagnosed between 2000 and 2012. We described sources of exposure to asbestos and examined time trends of MM rates. Using Poisson age-cohort models, we derived projections of burden of MM in the Lombardy population for the period 2013-2029. RESULTS: In 2000-2012, we recorded 4442 cases of MM (2850 men, 1592 women). Occupational exposure to asbestos was more frequent in men (73.6%) than in women (38.2%). Non-occupational exposure was found for 13.6% of women and 3.6% of men. The average number of cases of MM per year was still increasing (+3.6% in men, +3.3% in women). Incidence rates were still increasing in individuals aged 65+ years and declining in younger people. A maximum of 417 cases of MM (267 men, 150 women) are expected in 2019. We forecast there will be 6832 more cases (4397 in men, 2435 in women) in the period 2013-2029, for a total of 11 274 cases of MM (7247 in men, 4027 in women) in 30 years. CONCLUSIONS: This study documented a high burden of MM in both genders in the Lombardy Region, reflecting extensive occupational (mainly in men) and non-occupational (mainly in women) exposure to asbestos in the past. Incidence rates are still increasing; a downturn in occurrence of MM is expected to occur after 2019.

Geographical patterns of mesothelioma incidence and asbestos exposure in Lombardy, Italy.

BACKGROUND: Measuring malignant mesothelioma (MM) occurrence is a useful means to monitor the impact of past asbestos exposure and possibly identify new sources of asbestos exposure. OBJECTIVES: Aim of this study is to describe the results of the MM registry of the Lombardy Region, North-West Italy, the most populated (currently, 10 million inhabitants) and industrialised Italian region. METHODS: We extracted from the Lombardy Region Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) database all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in 2000 through 2012. For each Province, we calculated crude and standardised incidence rates using Italy 2001, European, and world (Segi's) standard populations. To examine spatial patterns of MM occurrence across municipalities we drew maps of crude rates smoothed according to the Besag, York and Mollié (BYM) method. RESULTS: We recorded 4442 MM cases (2850 in men and 1592 in women), representing about one fourth of MM cases occurring in Italy. Occupational exposure was more frequent in men (73.6%) than in women (38.2%). The crude regional rates were 4.7 per 100,000 person-years in men and 2.5 per 100,000 person-years in women. The highest rates were observed in the Pavia Province (crude rates: 8.7 per 100,000 in men and 5.3 and per 100,000 person-years in women). CONCLUSIONS: This study documented high MM occurrence in both genders, attributable to extensive asbestos exposure in the past.

[Malignant mesotheliomas with unknown exposure to asbestos: a re-examination]. / Mesoteliomi maligni con esposizione ad amianto ignota: un riesame a distanza.

INTRODUCTION: Malignant Mesothelioma (MM) is a rare neoplasm associated with asbestos exposure. In 24,5% of MM cases reported to the Lombardy Mesothelioma Registry (LMR), asbestos exposure has been defined as "unknown". OBJECTIVE: To evaluate the cases with "unknown exposure to asbestos" diagnosed in 2000-2004 in agreement with new knowledge about source of asbestos exposure. METHODS: Information regarding exposure has been reviewed in order to select the cases susceptible of further investigations, including: interview of relatives and/or colleagues; further evaluations by local PSAL (Prevention and Security in workplace) services; contact of industrial hygienists; analysis of production processes. The same procedure has been followed for extra-occupational exposure. These cases have been subjected to the LMR evaluation group. RESULTS: Fourthy four out of 364 (12,1%) MM have been reclassified. In 47,7% of the cases, a "possible occupational exposure" has been recognized, 15,9% have been attributed a "certain occupational exposure", while 36,4% an extra-occupational (domestic, environmental and leisure-time) exposure. No significant differences between age, sex, cancer site, diagnostic certainty, residence, year of diagnosis, interviewed subjects were detected. The occupational sector with the highest amount of reclassifications was the clothing production. CONCLUSIONS: The detailed reconstruction of clinical and occupational history and of lifestyle habits of patients affected by MM, close cooperation with Local Services of Occupational Medicine and literature review make it possible for previously overlooked asbestos exposure to be acknowledged.

[Workers with Ehlers-Danlos syndrome: indications for health surveillance and suitable job assignment]. / Lavoratori con syndrome di Ehlers-Danlos: indicazioni per la sorveglianza sanitaria e per un corretto inquadramento lavorativo.

BACKGROUNDS: In Europe 23.5% of the working-age population suffers from chronic or rare diseases, including Ehlers-Danlos syndrome (EDS), an inherited disorder of the connective tissue that frequently leads to impairment also at work. OBJECTIVES: We sought to evaluate the impairment of different functional areas in EDS subjects, using EDS-Disability Test (EDS-DT) (7 visual analogical scales: pain, stiffness, daily activities of life, in the home, outside the home, at work, in social relationships). METHODS: We administered the EDS-DT to 50 workers with EDS (classic type n=35, hypermobile n=14, vascular n=3) and 150 healthy workers (non-EDS). RESULTS: EDS subjects showed higher perceived disability (median 29.31 vs 7.22, p< 0.0001) than non-EDS. We observed a trend suggesting that the hypermobile type has a higher level of pain (54 vs 42) and work impairment (62.5 vs 42.5) (p>0.20), whereas the classic type has greater impairment of daily living activities (18.57 vs 11.43) and in the home (34.29 vs 25.71) (p>0.20). Subjects reporting moderate-to-vigorous occupational physical activities (OPA) showed a higher disability level in the work area (p=0.04). CONCLUSIONS: People with EDS suffer from chronic pain, impaired quality of life and employment difficulties. The hypermobile type seems more compromised in functional areas such as pain and work, while the classic type is more compromised in daily routine and home activities. The employment section was more impaired for EDS subjects who perform tasks with greater physical effort.

Susceptibility to particle health effects, miRNA and exosomes: rationale and study protocol of the SPHERE study.

BACKGROUND: Despite epidemiological findings showing increased air pollution related cardiovascular diseases (CVD), the knowledge of the involved molecular mechanisms remains moderate or weak. Particulate matter (PM) produces a local strong inflammatory reaction in the pulmonary environment but there is no final evidence that PM physically enters and deposits in blood vessels. Extracellular vesicles (EVs) and their miRNA cargo might be the ideal candidate to mediate the effects of PM, since they could be potentially produced by the respiratory system, reach the systemic circulation and lead to the development of cardiovascular effects.The SPHERE ("Susceptibility to Particle Health Effects, miRNAs and Exosomes") project was granted by ERC-2011-StG 282413, to examine possible molecular mechanisms underlying the effects of PM exposure in relation to health outcomes. METHODS/DESIGN: The study population will include 2000 overweight (25 < BMI < 30 kg/cm2) or obese (BMI ≥ 30 kg/cm2) subjects presenting at the Center for Obesity and Work (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy).Each subject donates blood, urine and hair samples. Extensive epidemiological and clinical data are collected. Exposure to PM is assigned to each subject using both daily PM10 concentration series from air quality monitors and pollutant levels estimated by the FARM (Flexible air Quality Regional Model) modelling system and elaborated by the Regional Environmental Protection Agency.The recruitment period started in September 2010 and will continue until 2015. At December 31, 2013 we recruited 1250 subjects, of whom 87% lived in the province of Milan.Primary study outcomes include cardiometabolic and respiratory health effects. The main molecular mechanism we are investigating focuses on EV-associated microRNAs. DISCUSSION: SPHERE is the first large study aimed to explore EVs as a novel potential mechanism of how air pollution exposure acts in a highly susceptible population. The rigorous study design, the availability of banked biological samples and the potential to integrate epidemiological, clinical and molecular data will also furnish a powerful base for investigating different complementary molecular mechanisms. Our findings, if confirmed, could lead to the identification of potentially reversible alterations that might be considered as possible targets for new diagnostic and therapeutic interventions.

Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register.

Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as "at risk" (asbestos-cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.