Analysis of Routine and Integrative Data from Clostridioides difficile Infection Diagnosis and the Consequent Observations

Abstract: Background: Clostridioides difficile Infection (CDI) is an acute disease that needs a fast proper treatment. Unfortunately, the diagnosis, and above all the understanding of the results, remain arduous. Objective: This study analyzed routine and integrative results of all fecal samples from patients over time. Our aim was to understand the dynamics of CDI infection and the meaning of \u201cdifficult to interpret\u201d results, to make physicians better understand the various tools they can use. Methods: We evaluated routine results obtained from 815 diarrheal stools with Enzyme Immunoassay (EIA) that detects C. difficile Glutamate Dehydrogenase (GDH) antigen and toxin B. We also reanalyzed a part of samples using integrative tests: a Real-time polymerase chain reaction (RT-PCR) for C. difficile toxin B gene (tcdB) and the automated immunoassay VIDAS C. difficile system for GDH and toxins A/B. Results: EIA GDH positivity increased through multiple testing over time, with a P value <0.001, depicting a sort of bacterial growth curve. Eighty-five percent of GDH positive/toxin B negative, i.e., discrepant, samples PCR were tcdB positive, 61.5% of discrepant tcdB positive samples were VIDAS toxins A/B positive, and 44.4% of GDH EIA negative stools were VIDAS GDH positive. Conclusion: The results confirmed the low sensitivity of the EIA system for C. difficile GDH and toxins, questioned the use of the latter for concluding any CDI diagnostic algorithm, and led us to indicate the algorithm beginning with tcdB molecular research, and continuing in positive cases with VIDAS CD GDH method, as the most effective for CDI

Reanalysis of updated mortality among vinyl and polyvinyl chloride workers: Confirmation of historical evidence and new findings

<p>Abstract</p> <p>Background</p> <p>The production of vinyl chloride (VC) and polyvinyl chloride (PVC) involves the use of various chemicals, some known to be toxic and potentially or definitely carcinogenic. The related potential risk often has not been properly investigated. Updated cancer mortality among different subgroups of workers employed in a VC-PVC production plant located in Porto Marghera (Italy) was re-analyzed using an internal reference group of workers with low (or null) exposure to VC.</p> <p>Methods</p> <p>Mortality of 1658 male workers was analyzed by Poisson regression. Relative risks (RRs) and 95% confidence intervals (CIs) for blue collar workers and their specific subgroups of PVC baggers, PVC compound, autoclave and other blue collar workers were calculated using technicians and clerks as an internal reference group. The follow-up covered the period 1972–1999.</p> <p>Results</p> <p>Significantly increased mortality rates were observed for all causes of death among the whole blue collar workforce (RR = 1.55; 95% CI = 1.03–2.35; 229 deaths), PVC baggers (1.72; 95% CI = 1.04–2.83; 49 deaths) and PVC compound workers (1.71; 95% CI = 1.09–2.67; 72 deaths). Liver cancer, including angiosarcoma, was increased among autoclave workers (9.57; 95% CI = 3.71–24.68; 7 deaths) and cardiovascular diseases among PVC baggers (2.25; 95% CI = 1.08–4.70; 12 deaths). Hemolymphopoietic system tumors, leukemias and lymphomas prevalently, were found only among exposed workers, with 4, 4 and 6 deaths observed among PVC baggers, PVC compound and other blue collar workers, respectively. An excess of lung cancer was found among PVC baggers.</p> <p>Conclusion</p> <p>This cohort analysis, based on internal comparison, confirmed previously reported specific risk excesses for liver tumors and liver cirrhosis among autoclave workers and for lung cancer among PVC baggers, and revealed PVC compound workers as a possible new at risk group for all causes, all tumors and for liver and lung tumors. In conclusion, RRs for all causes of death and all tumors were increased among all blue collar workers.</p

Epidemiology of Clostridium Difficile Infection in a Large Hospital in Northern Italy: Questioning the Ward-Based Transmission

Background: Clostridium Difficile infection (CDI) is considered a ward-based nosocomial infection, due to contagion among patients. Molecular studies recently questioned ward-based contact for disease spread. Objective: To investigate whether it is plausible that CDI spread in San Martino Hospital of Genoa was due to a ward-based contact and patientto- patient diffusion. Methods: We conducted a retrospective cohort study of CDI cases from April 2010 to March 2015. We referred to Hospital data set and Admission Service. Multilevel modelling approach and ecological analysis were used to assess C. difficile infection risk according to wards and time of occurrence. Six representative CD strains were ribotyped to assess a possible equivalence. Results: The assessment of 514 CDI cases showed that the risk of disease and rate of incidence in wards were independent, while frequency of cases and number of wards involved exhibited a positive relationship, excluding the typical epidemic pattern of contagious diffusion, i.e., many cases in few wards. The extra-binomial variability due to ward clustering was not significant, indicating homogeneity in the probability of CDI occurrence across all wards. Three hundred sixty-eight patients changed ward, without showing connection between the frequency of cases in new wards and incidence among new subjects. Trigonometric components described a significant contribution of seasonality, with excess of CDI cases during the winter months. Molecular analysis showed different ribotypes of CD strains from the same ward. Conclusion: From our results it seems unlikely that in our institution CDI occurrence is due to ward-based contact and inter-human contagion of the organism

Smoking, DNA Adducts and Number of Risk DNA Repair Alleles in Lung Cancer Cases, in Subjects with Benign Lung Diseases and in Controls

Smoke constituents can induce DNA adducts that cause mutations and lead to lung cancer. We have analyzed DNA adducts and polymorphisms in two DNA repair genes, for example, XRCC1 Arg194Trp and Arg399Gln genes and XRCC3 Thr241Met gene, in 34 lung cancer cases in respect to 30 subjects with benign lung cancer disease and 40 healthy controls. When the study population was categorized in base to the number of risk alleles, adducts were significantly increased in individuals bearing 3-4 risk alleles (OR = 4.1 95% C.I. 1.28–13.09, P = .009). A significant association with smoking was noticed in smokers for more than 40 years carrying 3-4 risk alleles (OR = 36.38, 95% C.I. 1.17–1132.84, P = .040). A not statistically significant increment of lung cancer risk was observed in the same group (OR = 4.54, 95% C.I. 0.33–62.93, P = .259). Our results suggest that the analysis of the number of risk alleles predicts the interindividual variation in DNA adducts of smokers and lung cancer cases

Malondialdehyde–Deoxyguanosine Adducts among Workers of a Thai Industrial Estate and Nearby Residents

Background: Humans living near industrial point emissions can experience high levels of exposures to air pollutants. Map Ta Phut Industrial Estate in Thailand is the location of the largest steel, oil refinery, and petrochemical factory complexes in Southeast Asia. Air pollution is an important source of oxidative stress and reactive oxygen species, which interact with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. Objective: We measured the levels of malondialdehyde-deoxyguanosine (dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in petrochemical workers, nearby residents, and subjects living in a control district without proximity to industrial sources. Design: We conducted a cross-sectional study to compare the prevalence of malondialdehyde-dG adducts in groups of subjects experiencing various degrees of air pollution. Results: The multivariate regression analysis shows that the adduct levels were associated with occupational and environmental exposures to air pollution. The highest adduct level was observed in the steel factory workers. In addition, the formation of DNA damage tended to be associated with tobacco smoking, but without reaching statistical significance. A non significant increase in DNA adducts was observed after 4-6 years of employment among the petrochemical complexes. Conclusions: Air pollution emitted from the Map Ta Phut Industrial Estate complexes was associated with increased adduct levels in petrochemical workers and nearby residents. Considering the mutagenic potential of DNA lesions in the carcinogenic process, we recommend measures aimed at reducing the levels of air pollution

Chromosomal Aberrations in Lymphocytes of Healthy Subjects and Risk of Cancer

There is evidence that increased frequency of chromosomal aberration (CA) in peripheral blood lymphocytes is a predictor of cancer, but further data are needed to better characterize CA as marker of cancer risk. From the archives of 15 laboratories we gathered cytogenetic records of 11,834 subjects who were free of cancer at the moment of blood drawing and who underwent cytogenetic examination for preventive purposes in the Czech Republic during 1975–2000. We linked these records to the national cancer registry, revealing a total of 485 cancer cases. Subjects were classified according to the percentiles of CA distribution within each laboratory as low (0–33rd percentile), medium (34–66th percentile), and high (66–100th percentile). Subjects were further classified by occupational exposure and by subclass of CA. We found a significant association between the overall cancer incidence and the presence of chromosome-type aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence interval (CI), 1.03–1.50] but not chromatid-type aberrations. Stomach cancer showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01–60.0). The predictivity of CA observed in subjects exposed to various classes of carcinogens did not significantly differ from the group of nonexposed subjects. This study contributes to validation of CA as a predictive marker of cancer risk, in particular, of stomach cancer; the association between CA frequency and cancer risk might be limited to chromosome-type aberrations

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Càncer de mama; Genètica del càncerCáncer de mama; Genética del cáncerBreast cancer; Cancer geneticsYoung breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.This study received partial financial support by grants from the Italian Ministry of Health - 5 × 1000 funds 2017 (no grant number), the Italian Association for Cancer Research (AIRC; MFAG 2020 ID 24698), and “Les Amis de l’Institut Bordet” foundation (no grant number). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. M.L. acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium) at the time of study conduction. K.P. acknowledges the support from a predoctoral clinical ‘KOOR’ mandate from the University Hospitals Leuven (Leuven, Belgium). F.P.D. acknowledges the support for a postdoctoral clinical mandate (2017-034) from the not-for-profit organization ‘Foundation Against Cancer’ (Brussels, Belgium). A.H.P. acknowledges the support from Susan G. Komen and Breast Cancer Research Foundation (BCRF). J.H. acknowledges the support from the Carlos III National Health Institute funded by FEDER funds—a way to build Europe (PI16/11363). This research was presented in the Poster Spotlight session at the 2020 San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, United States of America, on 8–12 December 2020

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer

Breast cancer fertility; Pregnancy; SurvivalFertilidad y cáncer de mama; Embarazo; SupervivenciaFertilitat i càncer de mama; Embaràs; SupervivènciaBackground Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. Patients and methods This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Results Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. Conclusion This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.The present work was supported by the Italian Association for Cancer Research (‘Associazione Italiana per la Ricerca sul Cancro’, AIRC; MFAG 2020 ID 24698) and the Italian Ministry of Health (5 × 1000 funds 2017). MC and ID acknowledge the Fonds National de la Recherche Scientifique (FNRS and Télévie 7.6508.20) and Fonds Erasme for their financial support

Baseline Micronuclei Frequency in Children: Estimates from Meta- and Pooled Analyses

The number of studies evaluating the effect of environmental exposure to genotoxic agents in children has rapidly increased in the last few years. The frequency of micronuclei (MN) in peripheral blood lymphocytes determined with the cytokinesis block assay is among the most popular biomarkers used for this purpose, although large inter- and intralaboratory variability of this end point has been observed in population studies. The availability of reference measures is therefore necessary for laboratories to validate protocols and analytical procedures, and for molecular epidemiologists, as well, to estimate the statistical power of studies and to assess the quality of data. In this article, we provide estimates of the baseline frequency of MN in children, conducting a meta-analysis of MN frequency reported by field studies in children and a pooled analysis of individual data [available from published studies and from the Human Micronucleus International Collaborative Study (HUMN) database]. Thirteen articles were selected for meta-analysis, and individual data included in the pooled analysis were retrieved from the databases of 12 laboratories. Overall means of 4.48 [95% confidence interval (CI), 3.35–5.98] and 5.70 (95% CI, 4.29–7.56) MN per 1,000 binucleated cells were estimated by the meta- and pooled analysis, respectively. A clear effect of age was detected, even within the restricted range of pediatric age considered, with significantly lower frequency values in newborns. No influence of sex was found. The study showed the advantage of using data from large collaborative studies and suggested a synergistic use of meta- and pooled analysis

Cancer incidence in pet dogs: findings of the Animal Tumor Registry of Genoa, Italy.

Background: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable reference populations. Objectives: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs. Methods: Six thousand seven hundred and forty-three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD-9). Results: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog-years (95% CI: 93.6–105.1) in male dogs and 272.1 (95% CI: 260.7–283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR = 191.8, 95% CI: 182.2–201.4) and for non-Hodgkin's lymphoma (IR = 22.9, 95% CI: 19.7–26.5) in bitches and for non-Hodgkin's lymphoma (IR = 19.9, 95% CI: 17.4–22.7) and skin cancer (IR = 19.1, 95% CI: 16.6–21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4–30.1) and 763.2 (95% CI: 700.4–830.1) in bitches and between 16.5 (95% CI: 12.8–21.1) and 237.6 (95% CI: 209.1–269.0) in male dogs aged ≤3 years and >9–11 years. Conclusion: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population