Quarantine and Mental Health Challenges for Occupational Medicine: The Case Report of a Nurse Infected With SARS-CoV-2.

This case study draws attention to the psychosocial difficulties that emerged in the context of the coronavirus disease 2019 (COVID-19) outbreak in relation to the remote management of subjects with psychiatric vulnerabilities following exposure to prolonged quarantine. The case involves a 56-year-old hospital nurse, followed by the Occupational Health Department of a major university hospital in central Italy for mood instability in the context of a cyclothymic temperament. She was quarantined for occupationally acquired COVID-19 and remained positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via swab test for more than 2 months between March and May 2020. In this case study, we discuss the challenges presented by the risk of a prolonged quarantine in a psychologically vulnerable employee, the need for occupational medicine to provide adequate health surveillance of all health care workers during the COVID-19 pandemic, the effectiveness of telepsychiatry, and the difficulties in formulating a proper treatment strategy.

CXCL8 and CXCL11 chemokine secretion in dermal fibroblasts is differentially modulated by vanadium pentoxide.

An increase in skin rashes or atopic dermatitis has been observed in individuals working with vanadium. However, to the best of our knowledge no in vivo or in vitro studies have evaluated the effect of exposure to vanadium in dermal fibroblasts. Cells viability and proliferation were assessed by WST­1 assay, cells were treated with increasing concentrations of V2O5 (1, 10 and 100 nM). CXCL8 and CXCL11 concentrations were measured in the supernatants using an ELISA assay. V2O5 was not observed as having a significant effect on dermal fibroblast's viability and proliferation. However, it was revealed that V2O5 was able to induce the secretion of CXCL8 and CXCL11 chemokines into dermal fibroblasts. V2O5 synergistically increased the effect of interferon (IFN)γ on CXCL11 secretion. In addition, V2O5 synergistically increased the effect of the tumor necrosis factor α on CXCL8 secretion and abolished the inhibitory effect of IFNγ. V2O5 induction of CXCL8 and CXCL11 chemokines may lead to the appearance and perpetuation of an inflammatory reaction into the dermal tissue. Further studies are required to evaluate dermal integrity and manifestations in subjects occupationally exposed, or living in polluted areas.

Induction of Th1 chemokine secretion in dermal fibroblasts by vanadium pentoxide.

Vanadium is a soft, silvery­grey metal with a number of different oxidation states. The most common commercial form of vanadium is vanadium pentoxide (V2O5). All vanadium compounds are considered toxic. An increase in skin rashes has been observed in certain vanadium workers, including the development of atopic dermatitis. However, to the best of our knowledge, no prior in vivo or in vitro studies have evaluated the effect of vanadium exposure in human dermal fibroblasts. The present study evaluated the effect of V2O5 on proliferation and chemokine secretion in dermal fibroblasts. The results revealed that V2O5 had no significant effect on the viability or proliferation of fibroblasts, however it was able to induce the secretion of T­helper (Th)1 chemokines from dermal fibroblasts, synergistically increasing the effect of important Th1 cytokines, including interferon­Î³ and tumor necrosis factor­α. Through these processes, V2O5 may lead to the induction and perpetuation of an inflammatory reaction in dermal tissue. The induction and perpetuation of inflammation in the dermis and the variety of involved candidate genes may be at the base of V2O5­induced effects following occupational and environmental exposures. Further studies are necessary to evaluate dermal integrity and manifestations in subjects who are occupationally exposed, or living in polluted areas.

Vanadium pentoxide induces the secretion of CXCL9 and CXCL10 chemokines in thyroid cells.

Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes. Our study demonstrated that V2O5 has no effect on thyroid follicular cell viability or proliferation, but it is able to induce the secretion of T-helper (Th)1 chemokines into the thyroid, synergistically increasing the effect of important Th1 cytokines such as interferon (IFN)γ and tumor necrosis factor (TNF)α. Through this process, V2O5 promotes the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are necessary to evaluate thyroid function, and nodules, in subjects occupationally exposed, or living in polluted areas.

High risk of brain tumors in military personnel: a case control study.

Scientific literature suggests a relationship between military occupation and the development of brain tumors, but no italian study has investigated on the impact of this job on the brain cancer morbidity. In this a study information were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 1999. The study has been conducted as a case-control study. 161, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 483 controls (with other non tumoral neurologic diseases: trauma, hemorrhagic brain disorders, aneurism, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (military vs. non-military occupation). A statistically significant association was seen between brain tumors and military occupation among evaluated patients (p=0.013). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

High risk of brain tumors in farmers: a mini-review of the literature, and report of the results of a case control study.

Even though a relationship between farmer work and the development of brain tumors was suggest by the scientific literature, a small number of italian studies investigate on the impact of this job on the cancer morbidity of farmer population. The informations about this case-control study were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 2000. One hundred and seventy-four, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 522 controls (with other non tumoral neurologic diseases: trauma, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (agricultural vs. non-agricultural). We observed a significant association among brain tumors and rural activity in evaluated patients (P=0.008). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer, particularly in regions where there is an intense agricultural activity and where pesticides are used. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

A Novel Panel of Serum Biomarkers for MPM Diagnosis.

Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.

[Identification and characterization of microRNA involving in malignant pleural mesothelioma]. / Identificazione e caratterizzazione dei microRNA coinvolti nel mesotelioma pleurico maligno.

One of the research areas of modern medicine is to work on the identification of biological markers, such as biomolecular ones, for neoplastic diseases from occupational origin. MiRNA, short RNA no-codifing sequences, are recently identified such as diagnostic markers in several type of cancer. For this reason, the aim of our study is to analyze the possible role of miRNA in malignant pleural mesothelioma, a rare and aggressive tumor with a strong resistance to conventional therapies and poor prognosis. Total RNA, containing also miRNA, was extracted, and RNA was retro-transcripted with specific primers. Then, miRNA expression was tested using real-time PCR method and particular probes for each miRNA. The RNU6B was used such as housekeeping gene, for data normalization. This work represents the first step for the identification of a specific miRNA pattern for MPM, which will be useful in the diagnosis of MPM and for a personalized therapeutic treatment.

[Preliminary study to evaluate the meaning of GGT fractions analysis in a population of workers previously exposed to asbestos]. / Studio preliminare volto all'inquadramento del significato preventive del dosaggio di frazioni di GGT in una popolazione di lavoratori ex-esposti ad Amianto.

The GGT enzyme, considered for years only as a marker of liver disease and alcohol abuse, has now revealed a risk of death for many causes. Through a molecular exclusion chromatography on FPLC system (Fast Protein Liquid Chromatography), it is possible to discriminate four fractions of GGT, defined according to the molecular weight: big-GGT, medium-GGT, small-GGT and free-GGT. The objective was to study the preventing meaning of GGT fractions for asbestos-related diseases. This study was conducted on 129 workers previously exposed to asbestos, 22 patients affected by Malignant Pleural Mesothelioma and 107 healthy workers. Our data demonstrated a statistical significant correlation between the fraction free-GGT with the presence of MPM, suggesting a possible role for this molecule as a biomarker for MPM diagnosis. However, being a preliminary study, further studies are warranted to confirm our results.

[Report of medical surveillance of workers exposed to asbestos at the Operative Unit of Occupational Medicine in Pisa]. / Attività di sorveglianza sanitaria dei lavoratori ex esposti ad amianto presso la Unità Operativa di Medicina Preventiva del Lavoro di Pisa.

We report our experience about the medical surveillance of 739 workers previously exposed to asbestos. They were observed during the period between January 2009 and May 2012. The diagnosis of 594 patients, that were observed for the first time, were analyzed in order to assess the presence of benign or malignant pulmonary diseases that is so found: 16.33% of benign pulmonary diseases related to asbestos, 17.84% benign pulmonary diseases not related to asbestos and 1% of malignant pulmonary diseases probably related to asbestos. The diagnosis of 221 patients, that were followed over time, were analyzed in order to assess the evolution in time: a new onset of pulmonary disease was found in the 2.26%, a worsening of the pulmonary disease was found in the 6.79%.

[Occupational health and safety and gender differences: need for the identification of an adequate risk assessment]. / Salute, sicurezza sul lavoro e differenze di genere: necessità di una adeguata valutazione dei rischi.

Recent legislation has made mandatory to perform the risk assessment taking into account gender differences. This should imply to consider not only the simple differences due to biologic difference between male and female workers, but also what is more related to the social role they really play in the current society. This second aspect of gender difference has not yet been addressed from a technical point of view. The University of Pisa in cooperation with INAIL has recently started a project aimed at identifying technical tools to perform a risk assessment which took into account gender difference.

[Study on the efficacy of personal protective equipment for skin against nicotine absorption through the skin route in tobacco workers]. / Verifica dell'efficacia protettiva dei dispositivi di protezione individuale per la cute, nei confronti dell'esposizione per via cutanea a nicotina, in operatori addetti alla lavorazione del tabacco.

During a previous assessment on the efficacy of some recently installed general dust extraction systems in a tuscan cigar manufacture line, both environmental and biologic monitoring were performed. Although the analysis of environmental samples supported the efficacy of the new general protection implant, these data did not parallel the results from the biologic monitoring, suggesting that nicotine skin absorption needed to be further investigated. We, therefore, carried out a study aimed at evaluating the efficacy of three different kind of PPE for skin (two nitrile gloves of different thickness and one latex glove), to be used by tobacco workers. The results of this study showed that the performance of these three materials in stopping nicotine transfer through the gloves was significantly different. The 0.22 mm thick nicotine gloves resulted, by far, the best gloves in protecting the workers' skin against nicotine exposure.

[Prevalence of thyroid disease in healthcare workers occupationally exposed to ionizing radiation at the University Hospital of Pisa]. / Prevalenza di patologie tiroidee negli operatori sanitari radioesposti dell'Azienda Ospedaliero Universitaria Pisana.

The study analyzes the prevalence of thyroid disease in 1960 healthcare workers, classified as occupationally exposed to ionizing radiation, who have worked at the University Hospital of Pisa. They underwent a medical surveillance protocol from January 2005 until Mars 2012 at the Operative Unit of Occupational Medicine. A positive history of thyroid disease was found in 221 persons, but only 110 (the 5.61% of the population) developed the disease during or after the occupational exposure. Benign thyroid diseases, found in 93 workers, were in order of frequency: Hashimoto's thyroiditis, nodular disease, Basedow's disease, multinodular goiter, subacute thyroiditis and hypothyroidism. Malignant thyroid diseases were found in 17 workers (the 0.87% of the total population), 15 workers suffered from the papillary histotype and 2 from the medullary histotype.

[Assessment of urinary cotinine in a group occupationally exposed to nicotine]. / Valutazione della cotinina urinaria in un gruppo di esposti professionalmente alla nicotina.

In a Tobacco processing company, located in central Italy, both air nicotine and, one of its metabolites, the urinary cotinine were assessed, as part of the evaluation of the effectiveness of recently implemented technical preventive controls. Urinary cotinine measurements ranged from 9,63 to 234,09 microg/gr creat. in non-smokers and from 178,79 to 2476,19 microg/gr creat. in smokers. Urinary cotinine proved useful as an exposure biological index especially in terms of population monitoring. On the contrary, the meaning of the measured values were less clear in single workers, because of significant both intra- and inter-individual variability.

[Methodology and results of an experience of medical surveillance of people previously exposed to asbestos in Tuscany]. / Metodologia e risultati di una esperienza toscana di sorveglianza sanitaria di ex-esposti.

Although medical surveillance of workers previously exposed to asbestos has been made mandatory by several laws since 1991 (recently confirmed by the law 81/08), neither the subject encharged of it nor the medical protocols have been yet established. In the absence of a specific regulation different medical protocols have been proposed by several centers often with no respect of ethical or radioprotectionist principles, such as some screening programs exclusively based on radiologic exams. With the aim of setting up a secondary preventive health program according both to a correct ethical and economic cost-effective balance, we followed up a cohort of 647 workers. The medical protocol included a physical exam, functional respiratory tests, thoracic Xray and low dose CT scans along with some experimental biologic markers such as mesothelin and osteopontin. All the mentioned tests were periodically administered to asbestos workers according to the individual level of risk. This risk-modulated preventive medical protocol allowed us to diagnose respiratory diseases in up to 39% of the investigated population, 2/3 of which were classified as asbestos-related occupational diseases. In conclusion our data suggest that the integration of different kind of exams, with limited use of radiology, is effective in the medical follow-up of asbestos-exposed workers. Regional health politics should begin to take into account this reported evidence.

[Psychiatric support of healthcare workers undergoing periodic health assessment]. / Supporto psichiatrico ai lavoratori della sanità sottoposti a sorveglianza sanitoria periodica.

INTRODUCTION: An integrated mental health surveillance program was developed by the department of occupational medicine at S. Chiara University Hospital in Pisa, Italy, in order to better assist and treat hospital staff suffering from psychiatric disorders in a preventive medical setting. MATERIAL AND METHODS: During the occupational medical surveillance of 4000 employees of S. Chiara Hospital in Pisa (Italy), 30 health care workers with psychiatric disorders were included in our program, which provided psycho-educational support and pharmacological treatment. Measures of effectiveness were: Clinical Global Impression (CGI scale) and a comparison between the average number of lost workdays due to mental illness before and after treatment. RESULTS: At the end of the observation period there was a decrease in the CGI severity score with a improved CGI score ranging from 1 to 2 and a reduction in absenteeism, from an annual average of 36.70 to 25.10 lost workdays. CONCLUSION: Our outcome measures data seem to indicate that a preventive medicine setting can offer effective psychiatric support that is better accepted and tolerated by health care workers and that this approach may reduce absenteeism.

[Epidemiologic surveillance in occupational bladder cancer: a Tuscan experience]. / Intervento di ricerca attiva delle neoplasie vescicali di origine professionale: una esperienza toscana.

The percentage of bladder cancer as occupational disease in West-Europe is of 5/10%, but only a few amount of them are recognized as occupational disease from INAIL. The above mentioned research project is realized in order to decrease the gap between expected and claimed cases of occupational disease and it is conducted with the collaboration of ASL of Pisa, ASL of Empoli, Azienda Ospedaliera Universitaria Pisana and INAIL. 677 patients with bladder cancer were interviewed by phone, among them 64 subjects had a working experience compatible with neoplastic risks because had a previous occupational exposure to aromatic amines and metal working fluids. These cases were discussed into a Medical Staff and 40 cases were considered "probable" for occupational disease, 18 "possible", 3 cases are suspended for more research, 3 cases are considered "no professional disease". The research allows finding out a great number of bladder cancer, increasing the total amount of workers with occupational disease. The integrated approach with the collaboration among different institutions is surely the best way to allow and guarantee a suitable and right protection of workers with occupational disease.

[Evaluation of a series of serum mesothelin in patients with pleural malignant mesothelioma]. / Valutazione di dosaggi seriati di mesotelina sierica in pazienti affetti da mesotelioma maligno della pleura.

Pleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.

[Medical surveillance of previously asbestos-exposed workers: report of a case of lung cancer with high level of serum mesothelin]. / Sorveglianza sanitaria degli ex- esposti ad amianto: riscontro di un caso di tumore polmonare in un soggetto con elevati valori di mesotelina.

Recently, the number of previously asbestos-exposed workers performing, at our department, medical exams aimed at an early diagnosis of asbestos-related tumors, has been progressively increasing. The diagnostical protocol we propose to these subjects include both radiological exams and some serum markers such as mesothelin and osteopontin. In this case-report we illustrate the history of a worker who, after having diagnosed a pulmonary asbestosis, developed a Lung Cancer. The significance of this case is based on the importance of the high mesothelin dosage which prompted further radiological exams resulting into the final diagnosis. In spite of the early diagnosis and treatment the patient finally died. Nevertheless, serum markers like mesothelin and osteopontin (especially the first) may result very helpful in monitoring and screening the population of workers previously exposed to asbestos.

[Serum mesothelin dosages in follow-up of previously exposed workers]. / Il dosaggio della mesotelina sierica nel follow-up dei lavoratori ex esposti ad amianto.

High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).