Club cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining.

OBJECTIVE: The effect marker club cell protein (CC16) is secreted by the epithelium of the small respiratory tract into its lumen and passes into the blood. Increased amounts of CC16 in serum are observed during acute epithelial lung injury due to air pollutants. CC16 in serum was determined as part of this cross-sectional study in underground potash miners on acute and chronic health effects from exposures to diesel exhaust and blasting fumes. METHODS: Nitrogen oxides, carbon monoxide, and diesel particulate matter were measured in 672 workers at a German potash mining site on a person-by-person basis over an early shift or midday shift, together with CC16 serum concentrations before and after the respective shift. CC16 concentrations and CC16 shift-differences were evaluated with respect to personal exposure measurements and other quantitative variables by Spearman rank correlation coefficients. CC16 shift-differences were modeled using multiple linear regression. Above-ground workers as reference group were compared to the exposed underground workers. RESULTS: Serum concentrations of CC16 were influenced by personal characteristics such as age, smoking status, and renal function. Moreover, they showed a circadian rhythm. While no statistically significant effects of work-related exposure on CC16 concentrations were seen in never smokers, such effects were evident in current smokers. CONCLUSION: The small airways of current smokers appeared to be vulnerable to the combination of measured work-related exposures and individual exposure to smoking. Therefore, as health protection of smokers exposed to diesel exhaust and blasting fumes, smoking cessation is strongly recommended.

Underground salt and potash workers exposed to nitrogen oxides and diesel exhaust: assessment of specific effect biomarkers.

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO2) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers' health. METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type. RESULTS: None of the above-ground workers exceeded the OEL for NO2 and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO2; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift. CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO2 or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.

Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.

BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases. METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI). RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen. CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Cancer risks of firefighters: a systematic review and meta-analysis of secular trends and region-specific differences.

PURPOSE: The objective of this study was to conduct a systematic review and meta-analysis to evaluate the cancer risks among firefighters in the time course and from different geographical areas. METHOD: A PubMed search was performed to identify cohort studies about cancer risk and firefighting presented with standardized incidence ratios (SIRs) or standardized mortality ratios (SMRs). Using random-effect models, meta-relative risk estimates (mSIRs, mSMRs) and 95% confidence intervals (CI) were assessed. Cohort studies with employment starting before 1950 were classified as "old", studies starting between 1950 and 1970 as "medium", and later studies as "new". RESULTS: The general cancer risk of firefighters was similar to the general population, but mSMR decreased over time (new studies: mSMR = 0.81, 95% CI 0.70-0.92). We observed an increase of mSIR for melanoma of the skin and prostate cancer as well as a decrease of mSIR for stomach cancer with later employment onset. For those cancer sites, we did not observe a secular trend of mSMRs. Regional differences between relative cancer risks were particularly observed for bladder cancer. CONCLUSIONS: Among other things, innovative firefighting techniques and better personal protective equipment have provided a safer and healthier working environment for firefighters over time leading to a reduction of overall cancer incidence and mortality ratios. Increased general preventive medical checkups and possible additional screenings for firefighters might have led to more findings of malignant melanoma of the skin and prostate cancer in the recent past.

Cancer in glass workers: a systematic review and meta-analysis.

PURPOSE: Due to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports. METHODS: We searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992. RESULTS: From a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97-1.59) and 1.41 (95% CI 1.11-1.77), respectively. The estimated odds ratio (mOR) from five case-control studies was 1.25 (95% CI 0.90-1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23-4.16) based on two cohort studies; the mOR from four case-control studies was 1.35 (95% CI 0.73-2.52). Reports on elevated cancer risks at other sites were not consistent. CONCLUSIONS: Only few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

Self-Reported Survey on Allergy Symptoms Among First-Year Students in Veterinary Medicine: A Preamble to the AllergoVet Cohort Study.

Practical work in veterinary medicine provides exposure to various allergens which could increase the risk of sensitization. With the ongoing prospective "AllergoVet" study, we are investigating patterns of allergic symptoms and sensitization among veterinary students. Here, we report the results of the introductory self-reported survey on the presence of allergies in the first-year students of veterinary medicine, who had begun their studies in the years 2013-2016. The survey included 553 students who answered a questionnaire (63% response rate, 83% female ratio). The median age was 20 years (IQR: 19-22 years). About half of the responders indicated an interest in participating in the prospective study ("candidates"). Those who were uninterested in participating were termed "noncandidates". A doctor's diagnosis of any kind of atopic disease was reported by every fourth student. Hay fever was reported by 71 (13%) and allergic asthma by 38 (6.9%) students. The prevalence of hay fever in "candidates" (n = 294) and "noncandidates" (n = 259) was 13.5% and 12.2%, respectively. Allergic asthma was reported by 9.9% of "candidates" and 3.5% of "noncandidates", the difference being significant (p = 0.003). We conclude that the prevalence of self-reported allergic symptoms in the first-year students of veterinary medicine is similar to that in the general population. Pre-existing allergic asthma may have increased the motivation for the enrolment into the longitudinal "AllergoVet-study".

Exposure to Welding Fumes, Hexavalent Chromium, or Nickel and Risk of Lung Cancer.

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988-1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 µg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 µg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

Incidence of malignant mesothelioma in Germany 2009-2013.

PURPOSE: The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce. METHODS: We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany. RESULTS: In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men. CONCLUSION: Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.

Calretinin as a blood-based biomarker for mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin. METHODS: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype. RESULTS: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00). CONCLUSIONS: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.

Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study.

BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detection of CNVs in tumor-free men. METHODS: The prospective UroScreen study was designed to investigate the performance of UroVysion™ and other tumor tests for the early detection of bladder cancer in chemical workers from 2003-2010. We analyzed a database compiling CNVs of chromosomes 3, 7, and 17 and at 9p21 that were detected in 191,434 exfoliated urothelial cells from 1,595 men. We assessed the accumulation of CNVs in 1,400 cells isolated from serial samples that were collected from 18 cancer cases up to the time of diagnosis. A generalized estimating equation model was applied to evaluate the influence of age, smoking, and urine status on CNVs in cells from tumor-free men. RESULTS: Tetrasomy of chromosomes 3, 7 and 17, and DNA loss at 9p21 were the most frequently observed forms of CNV. In bladder cancer cases, we observed an accumulation of CNVs that started approximately three years before diagnosis. During the year prior to diagnosis, cells from men with high-grade bladder cancer accumulated more CNVs than those obtained from cases with low-grade cancer (CNV < 2: 7.5% vs. 1.1%, CNV > 2: 16-17% vs. 9-11%). About 1% of cells from tumor-free men showed polysomy of chromosomes 3, 7, or 17 or DNA loss at 9p21. Men aged ≥50 years had 1.3-fold more cells with CNVs than younger men; however, we observed no further age-related accumulation of CNVs in tumor-free men. Significantly more cells with CNVs were detected in samples with low creatinine concentrations. CONCLUSIONS: We found an accumulation of CNVs during the development of bladder cancer starting three years before diagnosis, with more altered cells identified in high-grade tumors. Also, a small fraction of cells with CNVs were exfoliated into urine of tumor-free men, mainly exhibiting tetraploidy or DNA loss at 9p21. Whether these cells are preferentially cleared from the urothelium or are artifacts needs further exploration.

Dinitrotoluene exposure in the copper mining industry and renal cancer: a case-cohort study.

OBJECTIVES: To evaluate the association between dinitrotoluene (DNT) exposure and renal cancer in a case-cohort study. METHODS: This case-cohort study was conducted among men born between 1920 and 1974 (n=16 441) who were gainfully employed between 1953 and 1990 in one of two copper mines in Mansfeld, Saxony-Anhalt, former German Democratic Republic, and followed up till 31 December 2006. The study included 109 cases with renal cancer identified by record linkage with the Common Cancer Registry of the New Federal States of Germany (GKR) or by a network of pathology institutes. A comparison subcohort of 999 cohort members was selected at random from the total cohort. Duration and intensity of inhalation and dermal exposure to DNT were assessed on the basis of a job exposure matrix. A time-dependent Cox proportional hazards model modified for case-cohort design was used to assess the relationship between cumulative inhalation and dermal DNT exposure and renal cancer. RESULTS: Elevated risks were found for medium (HR=2.73; 95% CI 1.00 to 7.42) and high (HR=1.81; 95% CI 0.75 to 4.33) dermal exposure to DNT. Relative risks for medium inhalation exposure to DNT were not increased (HR=0.93; 95% CI 0.48 to 1.79) while relative risks for high inhalation exposure to DNT were elevated to 1.36 (95% CI 0.84 to 2.21). We found a statistically significant HR of 2.12 (95% CI 1.03 to 4.37) for combined medium or high inhalation and medium or high dermal exposure to DNT. CONCLUSIONS: According to our case-cohort study, dermal and inhalation exposure to DNT is associated with increased renal cancer risk.

Cancer incidence among workers occupationally exposed to dinitrotoluene in the copper mining industry.

PURPOSE: Epidemiological and toxicological studies point to a potential carcinogenic effect of dinitrotoluene (DNT), particularly with respect to renal and urothelial cancer. METHODS: The cohort comprised all men born between 1920 and 1974 (n = 16,441) who were gainfully employed between 1953 and 1990 in one of two underground copper mines in Mansfeld, Saxony-Anhalt, former German Democratic Republic, and who were followed up for cancer incidence, 1961-2005. Incident cancer cases were identified by record linkage with the Common Cancer Registry of the New Laender. Standardized incidence ratios (SIR) were calculated with the general population of Saxony-Anhalt as the reference. RESULTS: Standardized incidence ratios for all cancers were not significantly elevated in the cohort (SIR = 1.04; 95 % confidence intervals (CI) 0.96-1.14). We found an increase in lung cancer (SIR = 1.29; 1.13-1.46), but not in kidney cancer (SIR = 1.01; 95 % CI 0.79-1.27) or bladder cancer (SIR = 1.04; 95 % CI 0.82-1.30). Standardized incidence ratios stratified by duration of employment with DNT exposure indicated moderately increased risks for kidney and bladder cancer in cohort members with longer exposure. CONCLUSIONS: The SIR analysis of workers in the copper mining industry in comparison with the general population of Saxony-Anhalt overall did not indicate increased risks for renal or bladder cancer. However, results by years of exposure to DNT suggested weakly increased risks for outcomes of a priori interest, bladder and kidney cancer. A subsequent case-cohort analysis including expert assessment of DNT exposure and identification of additional cancer cases from a network of pathology institutes will provide further insight into a potential etiologic role of DNT in renal and urothelial cancer.

Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines.

PURPOSE: To validate urinary markers for the early detection of bladder cancer (BC) in chemical workers. METHODS: UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of the German Social Accident Insurance for active or retired workers with former exposure to aromatic amines. From 2003 to 2010, 1,609 men took part in voluntary annual screens. Cytology, the quantitative NMP22(®) assay, and UroVysion™ were applied to 7,091 urine samples. RESULTS: Fifteen out of 21 tumors were detected following test positivity. The UroVysion/NMP22 panel detected 14 out of 21 tumors versus 8 tumors with cytology alone (sensitivity 66.7 vs. 44.4 %, specificity 94.5 vs. 98.5 %). The sensitivity of the panel increased to 85.7 % in samples collected ≤12 months before diagnosis and when papillomas were excluded, compared to 58.3 % with cytology. About 3 % of NMP22 tests were false-positive. UroVysion results overlapped with cytology due to the preselection of atypical cells. NMP22 was less and UroVysion more frequently positive in diluted urine samples. Leukocytes confounded NMP22 but not UroVysion. The low incidence of BC in this study population yielded low positive predictive values of the markers and high costs per tumor detected with screening. CONCLUSIONS: UroVysion in combination with NMP22 detected more cases than cytology alone, at the expense of a lower specificity. High costs per detected case resulted from a lower BC incidence than in the past when levels of occupational exposure to aromatic amines were higher. Currently, it cannot be recommended to apply these markers for screening in asymptomatic workers. The increase in sensitivity is not balanced by the high costs of UroVysion and the false-positive tests of NMP22.

Changes in mental distress among employees during the three years of the COVID-19 pandemic in Germany.

OBJECTIVES: The COVID-19 pandemic changed the future of work sustainably and led to a general increase in mental stress. A study conducted during the second and third pandemic wave with a retrospective survey of the first wave among 1,545 non-healthcare workers confirmed an increase in anxiety and depression symptoms and showed a correlation with the occupational SARS-CoV-2 infection risk. This online follow-up survey aims to examine changes in mental distress as the pandemic progressed in Germany and to identify factors influencing potential changes. METHODS: Longitudinal data from 260 subjects were available for this analysis. Mental distress related to anxiety and depression symptoms, assessed by the Patient Health Questionnaire-4 (PHQ-4), and occupational risk factors were solicited at the end of 2022 and retrospectively at the fifth wave. Categorized PHQ-4 scores were modelled with mixed ordinal regression models and presented with odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: A previous diagnosis of a depressive or anxiety disorder was a strong risk factor for severe symptoms (OR 3.49, 95% CI 1.71-7.11). The impact of occupational SARS-CoV-2 infection risk on mental distress was increased, albeit failing to reach the formal level of statistical significance (high risk OR 1.83, 95% CI 0.59-5.63; probable risk OR 1.72, 95% CI 0.93-3.15). Mental distress was more pronounced in those with a previous diagnosis of anxiety and depression. Confirmed occupational risk factors were protective measures against occupational SARS-CoV-2 infection perceived as inadequate, chronic work-related stress, overcommitment, reduced interactions with fellow-workers, and work-privacy conflicts. CONCLUSIONS: The pandemic had a negative impact on anxiety and depression symptoms among the studied non-healthcare workers, particularly early in the pandemic, although this effect does not appear to be permanent. There are modifiable risk factors that can protect workers' mental health, including strengthening social interactions among employees and reducing work-privacy conflicts.

Combination of calretinin, MALAT1, and GAS5 as a potential prognostic biomarker to predict disease progression in surgically treated mesothelioma patients.

BACKGROUND: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival. METHODS: Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival. RESULTS: MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %. CONCLUSION: MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.

Chromosomal instability and bladder cancer: the UroVysion(TM) test in the UroScreen study.

UNLABELLED: What's known on the subject? and what does the study add?: UroVysion™ is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 locus in exfoliated urothelial cells. This cell-based test is time-consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay. OBJECTIVE: To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysion™ assay regarding screening. SUBJECTS AND METHODS: In all, 1609 men took part in the prospective study UroScreen. Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010. In all, 191 434 cells in 6517 UroVysion tests were analysed for copy number variations (CNV) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men. We assessed CNVs at single or multiple loci using polysomy indices (PIs, called multiple PI and PI 3, PI 7 and PI 17). We calculated Spearman's rank correlation coefficients (rs ) between these PIs and receiver operating characteristic (ROC) curves with areas under the curves (AUCs). We applied Cox regression to estimate hazard ratios (HRs) to assess the risk of developing bladder cancer. RESULTS: Nine out of 21 bladder tumours detected in 20 participants ('cases') had a positive UroVysion test, including seven high-grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually. No case was found because of a complete loss of 9p21 in at least 12 cells. There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between rs = 0.98 and rs = 0.99 in cases and between rs = 0.84 and rs = 0.88 in non-cases (P < 0.001). Associations were less pronounced with CNVs at 9p21 among cases and were lacking in non-cases. Estimates of the relative risk of DNA gain for developing a bladder tumour assessed with PIs (threshold 10% of cells) were 47.7 (95% confidence interval [CI] 18.3-124.1) for the multiple PI, 44.5 (95%CI 16.5-119.9) for PI 3, 34.7 (95%CI 13.1-92.1) for PI 7 and 52.4 (95%CI 20.7-132.6) for PI 17, as well as 7.9 (95%CI 3.0-20.6) for a complete loss of 9p21 (threshold 2.5% of cells), respectively. ROC analyses showed similar AUCs for multiple PI compared with PIs of single chromosomes 3, 7 and 17 (all AUCs between 0.79 and 0.80) and a lower AUC for a homozygous loss of 9p21 (AUC 0.72). CONCLUSIONS: The UroVysion assay showed a reasonable performance in detecting bladder cancer in the present study population and shared positive test results with cytology, which is much cheaper. A simpler, faster and cheaper version of the UroVysion assay might rely on the very strong correlations between gains at chromosomes 3, 7 and 17, resulting in a similar performance in detecting bladder cancer with single-probe PIs compared with the full set of these probes. Loss of 9p21 was less predictive for developing bladder cancer in UroScreen.