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1. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6⁺B helper T cells in systemic lupus erythematosus

Author

Facciotti, F., Larghi, P., Bosotti, R., Vasco, C., Gagliani, N., Cordiglierif, C., Mazzarag, S., Ranzani, V., Rottoli, E., Curti, S., Penatti, A., Karnani, B., Kobayashi, Y., Crosti, M., Bombaci, M., van Hamburg, J. P., Rossetti, G., Gualtierotti, R., Gerosa, M., Gatti, S., Torretta, S., Pignataro, L., Tas, S. W., Abrignani, S., Pagani, M., Grassi, F., Meroni, P. L., Flavell, R. A., and Geginat, J.

Published
2020

4. Maturation signatures of conventional dendritic cell subtypes in COVID-19 suggest direct viral sensing

Author

Marongiu, L, Protti, G, Facchini, F, Valache, M, Mingozzi, F, Ranzani, V, Putignano, A, Salviati, L, Bevilacqua, V, Curti, S, Crosti, M, Sarnicola, M, D'Angio, M, Bettini, L, Biondi, A, Nespoli, L, Tamini, N, Clementi, N, Mancini, N, Abrignani, S, Spreafico, R, Granucci, F, Marongiu L., Protti G., Facchini F. A., Valache M., Mingozzi F., Ranzani V., Putignano A. R., Salviati L., Bevilacqua V., Curti S., Crosti M., Sarnicola M. L., D'Angio M., Bettini L. R., Biondi A., Nespoli L., Tamini N., Clementi N., Mancini N., Abrignani S., Spreafico R., Granucci F., Marongiu, L, Protti, G, Facchini, F, Valache, M, Mingozzi, F, Ranzani, V, Putignano, A, Salviati, L, Bevilacqua, V, Curti, S, Crosti, M, Sarnicola, M, D'Angio, M, Bettini, L, Biondi, A, Nespoli, L, Tamini, N, Clementi, N, Mancini, N, Abrignani, S, Spreafico, R, Granucci, F, Marongiu L., Protti G., Facchini F. A., Valache M., Mingozzi F., Ranzani V., Putignano A. R., Salviati L., Bevilacqua V., Curti S., Crosti M., Sarnicola M. L., D'Angio M., Bettini L. R., Biondi A., Nespoli L., Tamini N., Clementi N., Mancini N., Abrignani S., Spreafico R., and Granucci F.

Abstract

Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, which negatively affects T-cell activation. The presence of effector T cells in patients with mild disease and dysfunctional T cells in severely ill patients suggests that adequate T-cell responses limit disease severity. Understanding how cDCs cope with SARS-CoV-2 can help elucidate how protective immune responses are generated. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures, with the upregulation of IFN-stimulated genes and IL-6 signaling pathways. Furthermore, comparison of cDCs between patients with severe and mild disease showed severely ill patients to exhibit profound downregulation of genes encoding molecules involved in antigen presentation, such as MHCII, TAP, and costimulatory proteins, whereas we observed the opposite for proinflammatory molecules, such as complement and coagulation factors. Thus, as disease severity increases, cDC2s exhibit enhanced inflammatory properties and lose antigen presentation capacity. Moreover, DC3s showed upregulation of anti-apoptotic genes and accumulated during infection. Direct exposure of cDC2s to the virus in vitro recapitulated the activation profile observed in vivo. Our findings suggest that SARS-CoV-2 interacts directly with cDC2s and implements an efficient immune escape mechanism that correlates with disease severity by downregulating crucial molecules required for T-cell activation.

Published
2022

6. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case–control study and epidemiological remarks

Author

Marinaccio, A., Consonni, D., Mensi, C., Mirabelli, D., Migliore, E., Magnani, C., Di Marzio, D., Gennaro, V., Mazzoleni, G., Girardi, P., Negro, C., Romanelli, A., Chellini, E., Grappasonni, I., Madeo, G., Romeo, E., Ascoli, V., Carrozza, F., Angelillo, I. F., Cavone, D., Tumino, R., Melis, M., Curti, S., Brandi, G., Mattioli, S., Iavicoli, S., Dallari, B., Pesatori, A. C., Riboldi, L., Merletti, F., Gangemi, M., Stura, A., Brentisci, C., Gilardetti, M., Benfatto, L., Canessa, P. A., Malacarne, D., Mazzucco, G., Campi, M. G., Fedeli, U., Bressan, V., Gioffre, F., Ballarin, M. N., Chermaz, C., D'Agostin, F., De Michieli, P., Mangone, L., Storchi, C., Sala, O., Badiali, A. M., Cacciarini, V., Giovannetti, L., Martini, A., Calisti, R., Pascucci, C., Stracci, F., Masanotti, G., Davoli, M., Cavariani, F., Ancona, L., Annunziata, A., Menegozzo, S., Napolitano, F., Pelullo, C. P., Vimercati, L., Cascone, G., Frasca, G., Giurdanella, M. C., Martorana, C., Nicita, C., Rollo, C. P., Spata, E., Dardanoni, G., Scondotto, S., Nieddu, V., Pergola, M., Stecchi, S., Marinaccio, A., Consonni, D., Mensi, C., Mirabelli, D., Migliore, E., Magnani, C., Di Marzio, D., Gennaro, V., Mazzoleni, G., Girardi, P., Negro, C., Romanelli, A., Chellini, E., Grappasonni, I., Madeo, G., Romeo, E., Ascoli, V., Carrozza, F., Angelillo, I. F., Cavone, D., Tumino, R., Melis, M., Curti, S., Brandi, G., Mattioli, S., Iavicoli, S., Dallari, B., Pesatori, A. C., Riboldi, L., Merletti, F., Gangemi, M., Stura, A., Brentisci, C., Gilardetti, M., Benfatto, L., Canessa, P. A., Malacarne, D., Mazzucco, G., Campi, M. G., Fedeli, U., Bressan, V., Gioffre, F., Ballarin, M. N., Chermaz, C., D'Agostin, F., De Michieli, P., Mangone, L., Storchi, C., Sala, O., Badiali, A. M., Cacciarini, V., Giovannetti, L., Martini, A., Calisti, R., Pascucci, C., Stracci, F., Masanotti, G., Davoli, M., Cavariani, F., Ancona, L., Annunziata, A., Menegozzo, S., Napolitano, F., Pelullo, C. P., Vimercati, L., Cascone, G., Frasca, G., Giurdanella, M. C., Martorana, C., Nicita, C., Rollo, C. P., Spata, E., Dardanoni, G., Scondotto, S., Nieddu, V., Pergola, M., Stecchi, S., Marinaccio A., Consonni D., Mensi C., Mirabelli D., Migliore E., Magnani C., Di Marzio D., Gennaro V., Mazzoleni G., Girardi P., Negro C., Romanelli A., Chellini E., Grappasonni I., Madeo G., Romeo E., Ascoli V., Carrozza F., Angelillo I.F., Cavone D., Tumino R., Melis M., Curti S., Brandi G., Mattioli S., Iavicoli S., Dallari B., Pesatori A.C., Riboldi L., Merletti F., Gangemi M., Stura A., Brentisci C., Gilardetti M., Benfatto L., Canessa P.A., Malacarne D., Mazzucco G., Campi M.G., Fedeli U., Bressan V., Gioffre F., Ballarin M.N., Chermaz C., D'agostin F., De Michieli P., Mangone L., Storchi C., Sala O., Badiali A.M., Cacciarini V., Giovannetti L., Martini A., Calisti R., Pascucci C., Stracci F., Masanotti G., Davoli M., Cavariani F., Ancona L., Annunziata A., Menegozzo S., Napolitano F., Pelullo C.P., Vimercati L., Cascone G., Frasca G., Giurdanella M.C., Martorana C., Nicita C., Rollo C.P., Spata E., Dardanoni G., Scondotto S., Nieddu V., Pergola M., Stecchi S., Marinaccio, Alessandro, Consonni, Dario, Mensi, Carolina, Mirabelli, Dario, Migliore, Enrica, Magnani, Corrado, Di Marzio, Davide, Gennaro, Valerio, Mazzoleni, Guido, Girardi, Paolo, Negro, Corrado, Romanelli, Antonio, Chellini, Elisabetta, Grappasonni, Iolanda, Madeo, Gabriella, Romeo, Elisa, Ascoli, Valeria, Carrozza, Francesco, Angelillo, Italo Francesco, Cavone, Domenica, Tumino, Rosario, Melis, Massimo, Curti, Stefania, Brandi, Giovanni, Mattioli, Stefano, and Iavicoli, Sergio

Subjects
medicine.medical_specialty, pericardial and tunica vaginalis testis, Epidemiology, Population, rare disease, national registry, medicine.disease_cause, Epidemiology, Italy, National registry, Rare disease, Asbestos, epidemiology, Italy, national registry, rare disease, NO, 03 medical and health sciences, 0302 clinical medicine, italy, medicine, epidemiology, Italy, Mesothelioma, education, Gynecology, education.field_of_study, business.industry, Public Health, Environmental and Occupational Health, Tunica vaginalis testis, Case-control study, case–control study, Odds ratio, medicine.disease, asbestos, 030210 environmental & occupational health, National registry, exposure, mesothelioma, malignant mesothelioma, Original Article, Public aspects of medicine, RA1-1270, business, Rare disease
Abstract

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.

Published
2020

8. The Morphosyntax Interface in Patients with Alzheimer's Disease

Author

Curti, S, Sanfelici, E, Curti, S., Curti, S, Sanfelici, E, and Curti, S.

Abstract

This paper investigates the morphological competence of Italian-speaking patients diagnosed with Alzheimer’s Disease (AD). More specifically, we test whether and how AD patients can apply the morphological operations involved in complex word formation, i.e., conversion and affixation. The aims are twofold: (i) to detect whether morphological operations are impaired in this population and (ii) to determine whether word formation rules can be a useful marker in AD diagnosis. Previous studies on AD have reported that patients are impaired in various linguistic domains, but little is known about whether and how morphology is affected. This study reports the results of a picture-supported sentence completion task administered to 20 AD patients (MMSE score 0-24) and 20 neurologically age- matched healthy subjects. We found that AD patients’ performance differed from that of neurologically age-matched healthy participants in both the rate of accuracy and the morphological processes exploited to create complex words. While AD patients apply both conversion and affixation, the former operation was selectively applied to create complex verbs derived from nouns and the latter was applied to compose complex nouns from verbs. We conclude that both the low rate of accuracy and the selective application of the two morphological processes distinguish AD patients from neurologically age-matched healthy subjects and can thus be taken as markers in AD diagnosis. From a theoretical viewpoint, our results may suggest that conversion is a form of affixation, as proposed in various studies, e.g., Bauer (2008).

Published
2021

9. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients

Author

Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., Abrignani S., Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., and Abrignani S.

Abstract

To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.

Published
2021

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

Author

Marinaccio A., Consonni D., Mensi C., Mirabelli D., Migliore E., Magnani C., Di Marzio D., Gennaro V., Mazzoleni G., Girardi P., Negro C., Romanelli A., Chellini E., Grappasonni I., Madeo G., Romeo E., Ascoli V., Carrozza F., Angelillo I. F., Cavone D., Tumino R., Melis M., Curti S., Brandi G., Mattioli S., Iavicoli S., Marinaccio, A., Consonni, D., Mensi, C., Mirabelli, D., Migliore, E., Magnani, C., Di Marzio, D., Gennaro, V., Mazzoleni, G., Girardi, P., Negro, C., Romanelli, A., Chellini, E., Grappasonni, I., Madeo, G., Romeo, E., Ascoli, V., Carrozza, F., Angelillo, I. F., Cavone, D., Tumino, R., Melis, M., Curti, S., Brandi, G., Mattioli, S., Iavicoli, S., Marinaccio A., Consonni D., Mensi C., Mirabelli D., Migliore E., Magnani C., Di Marzio D., Gennaro V., Mazzoleni G., Girardi P., Negro C., Romanelli A., Chellini E., Grappasonni I., Madeo G., Romeo E., Ascoli V., Carrozza F., Angelillo I.F., Cavone D., Tumino R., Melis M., Curti S., Brandi G., Mattioli S., and Iavicoli S.

Subjects
Mesothelioma, Tunica vaginalis testis, Economica, Letter, pericardial and tunica vaginalis testis (TVT), Socio-culturale, Ambientale, mesothelioma, ReNaM, Key terms: asbestos, Key terms: asbesto, Pericardium, Malignant mesothelioma
Abstract

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.

Published
2021

11. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus

Author

Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, Geginat J, Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, and Geginat J

Abstract

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (doublestranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Published
2020

12. POS0254 IMMUNE RESPONSE TO SARS-CoV-2 INFECTION IN PATIENTS WITH RHEUMATIC MUSCULOSKELETAL DISEASES: THE MAINSTREAM STUDY

Author

Favalli, E. G., primary, Favalli, A., additional, Andrea, G., additional, Maioli, G., additional, Zagato, E., additional, Bombaci, M., additional, Pesce, E., additional, Donnici, L., additional, Gruarin, P., additional, Biggioggero, M., additional, Curti, S., additional, Manganaro, L., additional, Marchisio, E., additional, Bevilacqua, V., additional, Martinovic, M., additional, Fabbris, T., additional, Sarnicola, M. L., additional, Crosti, M., additional, Marongiu, L., additional, Granucci, F., additional, Notabartolo, S., additional, Bandera, A., additional, Gori, A., additional, De Francesco, R., additional, Abrignani, S., additional, Caporali, R., additional, and Grifantini, R., additional

Published
2022
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15. Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure

Author

Magnani C., Silvestri S., Angelini A., Ranucci A., Azzolina D., Cena T., Chellini E., Merler E., Pavone V., Miligi L., Gorini G., Bressan V., Girardi P., Bauleo L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Mattioli S., Baldassarre A., Barone-Adesi F., Musti M., Mirabelli D., Pirastu R., Marinaccio A., Massari S., Ferrante D, Working Group, Ballarin MN, Brentisci C, Cortini B, Curti S, Gangemi M, Gioffrè F, Legittimo P, Mangone L, Marinelli F, Marinilli P, Panato C, Roncaglia F, Storchi C, Stura A, Vicentini M, Verdi S, Nannavecchia AM, Bisceglia L, Magnani C., Silvestri S., Angelini A., Ranucci A., Azzolina D., Cena T., Chellini E., Merler E., Pavone V., Miligi L., Gorini G., Bressan V., Girardi P., Bauleo L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Mattioli S., Baldassarre A., Barone-Adesi F., Musti M., Mirabelli D., Pirastu R., Marinaccio A., Massari S., Ferrante D, Working Group, Ballarin MN, Brentisci C, Cortini B, Curti S, Gangemi M, Gioffrè F, Legittimo P, Mangone L, Marinelli F, Marinilli P, Panato C, Roncaglia F, Storchi C, Stura A, Vicentini M, Verdi S, Nannavecchia AM, and Bisceglia L

Subjects
Risk, Mesothelioma, Lung Neoplasms, Pleural Neoplasms, Socio-culturale, Asbesto, Cohort Studies, Cause of Death, Occupational Exposure, Asbestos, Glassworks, Rolling stock, Shipyards, Humans, Industry, Peritoneal Neoplasms, Retrospective Studies, Mineral Fibers, Ovarian Neoplasms, Construction Materials, Ambientale, Italy, Urinary Bladder Neoplasms, Asbestosis, Glasswork, Female
Abstract

Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers.Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period.The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer.The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

Published
2020

16. Self-image, representation of the future, and school commitment in children and adolescents with learning disabilities [Rappresentazione di sé e del futuro e impegno scolastico in bambini e adolescenti con disturbo specifico dell’apprendimento]

Author

Magenes, Sara, Cancer, Alice, Curti, S, Monti, F, Antonietti, Alessandro, and Traficante, Daniela

Subjects
self-esteem, school commitment, Settore M-PSI/04 - PSICOLOGIA DELLO SVILUPPO E PSICOLOGIA DELL'EDUCAZIONE, positivity, self-efficacy, Learning disabilities
Published
2021

17. Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression

Author

Bonnal, R.J., Rossetti, G., Lugli, E., Simone, M. De, Gruarin, P., Brummelman, J., Drufuca, L., Passaro, M., Bason, R., Gervasoni, F., Chiara, G. Della, D'Oria, C., Martinovic, M., Curti, S., Ranzani, V., Cordiglieri, C., Alvisi, G., Mazza, E.M.C., Oliveto, S., Silvestri, Y., Carelli, E., Mazzara, S., Bosotti, R., Sarnicola, M.L., Godano, C., Bevilacqua, V., Lorenzo, M., Siena, S. Di, Bonoldi, E., Sartore-Bianchi, A., Amatu, A., Veronesi, G., Novellis, P., Alloisio, M., Giani, A., Zucchini, N., Opocher, E., Ceretti, A.P., Mariani, N., Biffo, S., Prati, D., Bardelli, A., Geginat, J., Lanzavecchia, A., Abrignani, S., Pagani, M., Bonnal, R.J., Rossetti, G., Lugli, E., Simone, M. De, Gruarin, P., Brummelman, J., Drufuca, L., Passaro, M., Bason, R., Gervasoni, F., Chiara, G. Della, D'Oria, C., Martinovic, M., Curti, S., Ranzani, V., Cordiglieri, C., Alvisi, G., Mazza, E.M.C., Oliveto, S., Silvestri, Y., Carelli, E., Mazzara, S., Bosotti, R., Sarnicola, M.L., Godano, C., Bevilacqua, V., Lorenzo, M., Siena, S. Di, Bonoldi, E., Sartore-Bianchi, A., Amatu, A., Veronesi, G., Novellis, P., Alloisio, M., Giani, A., Zucchini, N., Opocher, E., Ceretti, A.P., Mariani, N., Biffo, S., Prati, D., Bardelli, A., Geginat, J., Lanzavecchia, A., Abrignani, S., and Pagani, M.

Abstract

Item does not contain fulltext

Published
2021

18. Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy

Author

Girardi P., Merler E., Ferrante D., Silvestri S., Chellini E., Angelini A., Luberto F., Fedeli U., Oddone E., Vicentini M., Barone-Adesi F., Cena T., Mirabelli D., Mangone L., Roncaglia F., Sala O., Menegozzo S., Pirastu R., Azzolina D., Tunesi S., Miligi L., Perticaroli P., Pettinari A., Cuccaro F., Nannavecchia A. M., Bisceglia L., Marinaccio A., Pavone V. L. M., Magnani C., Working Group, Ancona L., Baldassarre A., Brentisci C., Cortini B., Curti S., Gangemi M., Gorini G., Legittimo P., Marinelli F., Marinilli P., Bressan V., Mattioli S., Ranucci A., Romeo E., Scarnato C., Storchi C., Stura A., Verdi S., Girardi P., Merler E., Ferrante D., Silvestri S., Chellini E., Angelini A., Luberto F., Fedeli U., Oddone E., Vicentini M., Barone-Adesi F., Cena T., Mirabelli D., Mangone L., Roncaglia F., Sala O., Menegozzo S., Pirastu R., Azzolina D., Tunesi S., Miligi L., Perticaroli P., Pettinari A., Cuccaro F., Nannavecchia A.M., Bisceglia L., Marinaccio A., Pavone V.L.M., Magnani C., Working Group, Ancona L., Baldassarre A., Brentisci C., Cortini B., Curti S., Gangemi M., Gorini G., Legittimo P., Marinelli F., Marinilli P., Bressan V., Mattioli S., Ranucci A., Romeo E., Scarnato C., Storchi C., Stura A., and Verdi S.

Subjects
Male, Asbestos, Serpentine, Asbestosis, Cumulative Exposure, Asbesto, cohort mortality study, medicine.disease_cause, Asbestos, Settore MED/01 - Statistica Medica, NO, 03 medical and health sciences, asbestos exposure, 0302 clinical medicine, Occupational Exposure, Chrysotile, Medicine, Humans, 030212 general & internal medicine, Asbestos-related diseases, Asbestos-related disease, business.industry, Asbestos exposure, Cohort mortality study, Retrospective assessment, asbestos-related diseases, asbestosis, retrospective assessment, Public Health, Environmental and Occupational Health, Asbestosi, Middle Aged, medicine.disease, 030210 environmental & occupational health, Asbestos cement, Cohort effect, Italy, Cohort, Female, business, Settore SECS-S/01 - Statistica, Demography, Human
Abstract

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.

Published
2019

19. Systematic reviews in occupational health and safety: Where are we and where should we go?

Author

Verbeek, J., Mattioli, S., Curti, S., Verbeek J., Mattioli S., and Curti S.

Subjects
Systematic reviews, effectiveness of interventions, effects of exposures, Sitting Position, Revisioni sistematiche, education, effetti delle esposizioni, Reproducibility of Results, Reproducibility of Result, Systematic reviews, effects of exposures, Effectiveness of intervention, NO, Effects of exposure, Systematic review, Humans, Original Article, effectiveness of interventions, Occupational Health, Revisioni sistematiche, efficacia degli interventi, effetti delle esposizioni, efficacia degli interventi, Human, Systematic Reviews as Topic
Abstract

Systematic Reviews have been introduced to improve the synthesis of available evidence and to reduce bias in the conclusions about a body of evidence. Nowadays, Systematic Review is an established method also in the Occupational Safety and Health (OSH) field. It is the Cochrane Work Review Group that facilitates authors to produce Cochrane reviews of intervention topics in this area. A variety of guidelines used Cochrane Work reviews for underpinning their recommendations. Due to the comprehensive search and reproducibility of the methods of a systematic review, it turned out that systematic reviews can be powerful in changing beliefs. For example, studies published in the eighties advocated the use of back schools. Nowadays, we know that the total body of evidence has changed the traditional view that training in lifting techniques could prevent back pain. 'Sitting is the new smoking' is an eye catching nicely alliterating motto, but it is of course highly overstated. The findings of a Cochrane review of the effects of interventions to decrease sitting at work showed that sitting time can be reduced by a bit less than two hours per day by providing sit-stand desks plus education. However, it is unclear if this is sufficient to counter the effects of sitting. A wealth of evidence on OSH interventions has been collected by international collaboration in the Cochrane Work Review Group. This can be extended to systematic reviews of the effects of exposure of workers to assess to which risks of adverse health effects they are exposed.

Published
2019

20. Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy

Author

Luberto F., Ferrante D., Silvestri S., Angelini A., Cuccaro F., Nannavecchia A. M., Oddone E., Vicentini M., Barone-Adesi F., Cena T., Mirabelli D., Mangone L., Roncaglia F., Sala O., Menegozzo S., Pirastu R., Azzolina D., Tunesi S., Chellini E., Miligi L., Perticaroli P., Pettinari A., Bressan V., Merler E., Girardi P., Bisceglia L., Marinaccio A., Massari S., Magnani C., Working group, Curti S., Mattioli S., Luberto F., Ferrante D., Silvestri S., Angelini A., Cuccaro F., Nannavecchia A.M., Oddone E., Vicentini M., Barone-Adesi F., Cena T., Mirabelli D., Mangone L., Roncaglia F., Sala O., Menegozzo S., Pirastu R., Azzolina D., Tunesi S., Chellini E., Miligi L., Perticaroli P., Pettinari A., Bressan V., Merler E., Girardi P., Bisceglia L., Marinaccio A., Massari S., Magnani C., Working group, Curti S., and Mattioli S.

Subjects
Male, Mesothelioma, Asbestos, Asbestos-cement, Dose response relationship, Mesothelioma, Lung cancer, Ovarian Cancer, Epidemiology, Time Factors, Epidemiology, Health, Toxicology and Mutagenesis, Asbestosis, Physiology, Cumulative Exposure, medicine.disease_cause, Cohort Studies, Neoplasms, Chrysotile, Asbestos-related diseases, 0303 health sciences, lcsh:Public aspects of medicine, Middle Aged, Asbestos-cement, Asbestos cement, Ovarian Cancer, Italy, Dose response relationship, lcsh:Industrial medicine. Industrial hygiene, Female, Lung cancer, Settore SECS-S/01 - Statistica, Adult, Asbesto, Asbestos, Settore MED/01 - Statistica Medica, NO, 03 medical and health sciences, lcsh:RC963-969, Young Adult, Sex Factors, Occupational Exposure, medicine, Humans, business.industry, Research, Public Health, Environmental and Occupational Health, 030311 toxicology, lcsh:RA1-1270, medicine.disease, business
Abstract

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.

Published
2019

21. Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies

Author

Barone-Adesi F., Ferrante D., Chellini E., Merler E., Pavone V., Silvestri S., Miligi L., Gorini G., Bressan V., Girardi P., Ancona L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Curti S., Baldassarre A., Cena T., Angelini A., Marinaccio A., Mirabelli D., Musti M., Pirastu R., Ranucci A., Magnani C., Working Group, Mattioli S., Barone-Adesi F., Ferrante D., Chellini E., Merler E., Pavone V., Silvestri S., Miligi L., Gorini G., Bressan V., Girardi P., Ancona L., Romeo E., Luberto F., Sala O., Scarnato C., Menegozzo S., Oddone E., Tunesi S., Perticaroli P., Pettinari A., Cuccaro F., Curti S., Baldassarre A., Cena T., Angelini A., Marinaccio A., Mirabelli D., Musti M., Pirastu R., Ranucci A., Magnani C., Working Group, and Mattioli S.

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Time Factors, Time Factor, Adolescent, Pleural Neoplasms, asbestos, epidemiology, mesothelioma, Asbesto, medicine.disease_cause, Asbestos, Settore MED/01 - Statistica Medica, NO, 03 medical and health sciences, Peritoneal Neoplasm, Young Adult, 0302 clinical medicine, Internal medicine, Occupational Exposure, Epidemiology, medicine, Humans, Pleural Neoplasm, Mesothelioma, Young adult, Peritoneal Neoplasms, business.industry, Public Health, Environmental and Occupational Health, Cancer, asbestos, epidemiology, mesothelioma, Adolescent, Adult, Italy, Middle Aged, Models, Theoretical, medicine.disease, 030210 environmental & occupational health, Occupational Disease, Occupational Diseases, asbestos, epidemiology, mesothelioma, Italy, 030220 oncology & carcinogenesis, Female, business, Human, Cohort study
Abstract

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.

Published
2019

25. Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6 + B helper T cells in systemic lupus erythematosus

Author

Facciotti, F., primary, Larghi, P., additional, Bosotti, R., additional, Vasco, C., additional, Gagliani, N., additional, Cordiglieri, C., additional, Mazzara, S., additional, Ranzani, V., additional, Rottoli, E., additional, Curti, S., additional, Penatti, A., additional, Karnani, B., additional, Kobayashi, Y., additional, Crosti, M., additional, Bombaci, M., additional, van Hamburg, J. P., additional, Rossetti, G., additional, Gualtierotti, R., additional, Gerosa, M., additional, Gatti, S., additional, Torretta, S., additional, Pignataro, L., additional, Tas, S. W., additional, Abrignani, S., additional, Pagani, M., additional, Grassi, F., additional, Meroni, P. L., additional, Flavell, R. A., additional, and Geginat, J., additional

Published
2020
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27. I DELITTI DI MANOMISSIONE DI CADAVERE

Author

Lupariello, F., Tattoli, L., Cena, G., Bosco, C., Curti, S., and Di Vella, G.

Subjects
distruzione, occultamento, sottrazione, vilipendio, distruzione, soppressione, sottrazione, occultamento, uso illegittimo di cadavere, vilipendio, uso illegittimo di cadavere, soppressione
Published
2019

29. I DELITTI CONTRO LA FAMIGLIA

Author

Tattoli, L., Bosco, C., Lupariello, F., Cena, G., Curti, S., and Di Vella, G.

Subjects
abuso dei mezzi di correzione o di disciplina, incesto, abuso dei mezzi di correzione o di disciplina, maltrattamenti nei confronti di familiari o conviventi, incesto, maltrattamenti nei confronti di familiari o conviventi
Published
2019

33. I DELITTI DI ABORTO

Author

Cena, G., Tattoli, L., Bosco, C., Curti, S., Lupariello, F., and Di Vella, G.

Subjects
aborto illegale
Published
2019

38. Documento di consenso. Il Medico del Lavoro nell’iter diagnostico e nella gestione degli obblighi documentali per le malattie lavoro-correlate. Strumenti di orientamento e aggiornamento in Medicina del Lavoro, Società Italiana di Medicina del Lavoro ed Igiene Industriale (SIMLII)

Author

Baldasseroni, A., Bertazzi, Pa, Campo, G., Clemente, M., Colosio, C., Curti, S., Ferrari, F., Deidda, B., Farioli, A., Fostinelli, J., Giachino, Gm, Goggiamani, A., L Madeo G, Isolani, Stefano Mattioli, Mancini, G., Pietroiusti, A., Riboldi, L., Romano, C., Soleo, L., Violante, Fs, and Baldasseroni A, Bertazzi PA, Campo G, Clemente M, Colosio C, Curti S, De Ferrari F, Deidda B, Farioli A, Fostinelli J, Giachino GM, Goggiamani A, Isolani L Madeo G, Mattioli S, Mancini G, Pietroiusti A, Riboldi L, Romano C, Soleo L, Violante FS.

Subjects
Economica, medicina del lavoro, fattori di rischio, malattie professionali, malattie da lavoro, iter diagnostico, malattie da lavoro, Socio-culturale, fattori di rischio, iter diagnostico, medicina del lavoro, malattie professionali
Abstract

Nel contesto legislativo attuale si colloca l'iniziativa della SIML che cerca, attraverso l'istituzione di un gruppo di lavoro specifico, di mettere a fuoco ed aggiornare i molteplici aspetti (diagnostici, medico-legali, previdenziali) coinvolti nel problema delle malattie lavoro-correlate

Published
2017

39. Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments

Author

Tavolari, S., primary, Deserti, M., additional, Vasuri, F., additional, Curti, S., additional, Palloni, A., additional, Pinna, A.D., additional, Cescon, M., additional, Frega, G., additional, De Lorenzo, S., additional, Barbera, M.A., additional, Garajova, I., additional, Ricciardiello, L., additional, Malvi, D., additional, D'Errico-Grigioni, A., additional, Pantaleo, M.A., additional, and Brandi, G., additional

Published
2019
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40. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Author

Facciotti, F., Larghi, P., Bosotti, R., Vasco, C., Gagliani, N., Cordiglieri, C., Mazzara, S., Ranzani, V., Rottoli, E., Curti, S., Penatti, A., Karnani, B., Kobayashi, Y., Crosti, M., Bombaci, M., van Hamburg, J. P., Rossetti, G., Gualtierotti, R., Gerosa, M., and Gatti, S.

Subjects
T helper cells, SYSTEMIC lupus erythematosus, B cells, CELL populations, IMMUNOGLOBULIN G
Abstract

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (doublestranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Il Sistema di Sorveglianza MALPROF

Author

Campo, G., Curti, S., Stefano Mattioli, Campo G, Curti S, and Mattioli S

Subjects
Economica, Malattie professionali, Socio-culturale, MALPROF, Sistema di sorveglianza
Abstract

Il Sistema di sorveglianza delle malattie professionali, denominato MALPROF, avviato in una fase sperimentale in Lombardia ed in Toscana, ad inizio degli anni 2000, ed in anni successivi esteso ad altre Regioni, è stato sostenuto dal 2007 dal Ministero della Salute al fine di attivare un sistema di sorveglianza esteso su scala nazionale gestito dall’INAIL. Tale sistema, nel raccogliere e classificare le segnalazioni di malattie lavoro-correlabili che pervengono ai Servizi di Prevenzione delle ASL, utilizza un modello di analisi per l’attribuzione dell’eventuale nesso di causa in funzione delle informazioni disponibili sull’anamnesi lavorativa e sulla qualità della diagnosi.

Published
2014

46. Patologie muscoloscheletriche in agricoltura

Author

Stefano Mattioli, Curti, S., Argentino, A., Violante, Fs, Mattioli S, Curti S, Argentino A, and Violante FS

Subjects
Economica, MUSCULOSKELETAL DISEASES, immune system diseases, Agricultural Workers' Disease, Socio-culturale, food and beverages, BIOMECHANICAL OVERLOAD, Agricultural Workers' Diseases, respiratory tract diseases
Abstract

Musculoskeletal disorders are a relevant issue among farmers. From the literature it emerges a convincing evidence for an association of arthritis of the hip and work in the agricultural sector, while there is a less evidence when studying knee osteoarthritis and farming. For what concerns cervicobrachial pain, current available epidemiological data are not sufficient to define farmers at risk. Moreover, there is uncertainty about the role of hand-arm vibration as a strong risk factor among farmers. Overall, the high occurrence of musculoskeletal disorders among farmers highligths the need for more specific studies in order to assess the various tasks performed by agricultural workers from which to derive appropriate prevention interventions.

Published
2013

47. Retinal detachment and occupational lifting: rediscovering lost knowledge

Author

Stefano Mattioli, Curti, S., Farioli, A., Violante, Fs, Mattioli S, Curti S, Farioli A, and Violante FS

Subjects
LIFTING, Economica, MANUAL WORK, Socio-culturale, RETINAL DETACHMENT
Abstract

Retinal detachment (RD) is the separation of the neurosensory retina from the underlying retinal pigment epithelium. Studies of the incidence of RD give estimates ranging from 6.3 to 17.9 cases per 100.000 person-years. We hypothesize that the Valsalva manoeuvre performed during lifting might increase the risk of RD. However, little is known about the changes in intraocular pressure during lifting. Experimental studies should be carried out to study the dose–response relationship between the lifted weight and the increase in intraocular pressure, also taking into account personal factors (e.g. gender, body shape) and working conditions (e.g. frequency of lifting, posture). There is also no firm epidemiological evidence about the exposure–response relationship between lifting tasks and the risk of RD. Future studies should investigate the time window between the exposure and occurrence of the disease. Finally, retinal diseases and their risk factors should be added to the criteria for the evaluation of fitness to work for jobs involving manual material handling.

Published
2013

49. Linee Guida per la prevenzione dei disturbi e delle patologie muscoloscheletriche del rachide da movimentazione manuale dei carichi

Author

Violante, Fs, Bonfiglioli, R., Graziosi, F., Stefano Mattioli, Brach Del Prever, E., Baracco, A., Romano, C., Perbellini, L., Bovenzi, M., Draicchio, F., Baldasseroni, A., Camagni, A., Curti, S., Farioli, A., Zanardi, F., Apostoli, P., Violante FS, Bonfiglioli R, Graziosi F, Mattioli S, Brach del Prever E, Baracco A, Romano C, Perbellini L, Bovenzi M, Draicchio F, Baldasseroni A, Camagni A, Curti S, Farioli A, Zanardi F, and Apostoli P

Subjects
Economica, VALUTAZIONE DEL RISCHIO, movimentazione manuale carichi, Socio-culturale, DISTURBI MUSCOLOSCHELETRICI
Abstract

La prima edizione delle Linee Guida SIMLII sul rischio associato alla movimentazione manuale di carichi è stata pubblicata nel maggio 2004. Da allora sia in campo scientifico che legislativo si sono verificate numerose novità che hanno imposto una nuova edizione delle Linee Guida stesse. La movimentazione manuale di carichi è un compito lavorativo (e non) che può essere associato a un rischio per la salute (a causa di un possibile sovraccarico biomeccanico) e di questo un medico del lavoro dovrebbe comunque occuparsi, indipendentemente dall’eventuale esistenza di specifici obblighi normativi.

Published
2012

50. EFFECTIVENESS OF A GLOBAL POSTURE REEDUCATION PROGRAM FOR PATIENTS WITH LOW BACK PAIN

Author

Bonetti, F., Curti, M., Curti, S., Ferrari, C., Stefano Mattioli, Mugnai, R., Pasanisi, C., Vanti, C., Pillastrini, P., Bonetti F., Curti M., Curti S., Ferrari C., Mattioli S., Mugnai R., Pasanisi C., Vanti C., and Pillastrini P.

Subjects
BACK, Economica, LOW BACK, Socio-culturale, EPIDEMIOLOGY, INTERVENTION STUDIES
Abstract

Purpose: Aim of this study was to evaluate the effectiveness of a Global Posture Reeducation (GPR) program in comparison to a physical therapy Standard Treatment (ST) in patients with low back pain (LBP) at short- and long-term follow-up (i.e. 3 and 6 months). Relevance: To our knowledge, this is the first controlled study comparing a GPR program to a physical therapy ST in patients with chronic LBP. Participants: 100 consecutive patients with a primary complaint of LBP were included in the study: 50 entered the GPR group and 50 entered the ST group. Methods: A multicentre, prospective, non-randomized, rater-blinded study was conducted between March 2008 and September 2009. Primary outcome measures were Roland and Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI). Secondary outcome measures were lumbar Visual Analogical Scale (VAS) and Fingertip-to- Floor test (FFT). Outcome measures were captured at baseline and at 3/6 months by a physical therapist blind to group allocation. Both groups received a treatment delivered by experienced physical therapists; and the number of sessions, the duration of each session and the total amount of treatment were identical. Moreover, both treatments consisted of a one-to-one supervised exercise program actively involving the patient. Analysis: Continuous data were expressed as means and standard deviations (SD), while categorical data were presented as absolute numbers and percentages (%). In order to compare the baseline characteristics of the GPR and ST group, the Student’s t test was used for continuous variables, whereas categorical variables were assessed using the X2 test or the Fisher’s exact test, as appropriate. An intention to treat approach was used to analyze participants according to the group to which they were originally randomly assigned. The way of dealing with missing data was substitution with data of the 3rd-month follow-up (when available for the subject) and with the mean of the non-worsened subjects in ST group and of the non-improved subjects in RPG group. Results: Of the 100 initial participants, 78 completed the study, 42 in GPR and 36 in ST group, respectively. At baseline, the two groups did not differ significantly with respect to gender, age, BMI and outcome measures. At the 6th-month follow-up, when examining differences from baseline, the RPG group revealed a significant reduction of all the outcome measures with respect to ST Group. Conclusions: Our findings point to the relevance of a GPR intervention performed by a physical therapist in improving pain, disability and flexibility as opposed to a ST program, in patients with LBP. These results must be confirmed by further studies with higher methodological standards, including randomisation, large sample size, long-term follow-up and initial clinical assessment for subgrouping classification. Implications: When considering the clinical impact of our research, we can state that the GPR program produced a clinically meaningful improvement. In fact, 48% of subjects in the GPR group obtained a reduction of at least 30% in their RMDQ and VAS scores, compared to the 12% in the ST group.

Published
2011

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