The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p′p,p'-DDE

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and $p,p'$-DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and $p$-value for trend were, respectively, 1.00, 1.68, 2.35, and $p$-value = 0.03) and morphology (1.00, 1.36, 2.53, $p$-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between $p,p'$-DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners

Artificial intelligence: The opinions of radiographers and radiation therapists in Ireland

Introduction: Implementation of Artificial Intelligence (AI) into medical imaging is much debated. Diagnostic Radiographers (DRs) and Radiation Therapists (RTTs) are at the forefront of this technological leap, thus an understanding of their views, in particular changes to their current roles, is key to safe, optimal implementation. Methods: An online survey was designed, including themes: role changes, clinical priorities for AI, patient benefits, and education. It was distributed nationally in the Republic of Ireland via the national professional body, clinical management, and social media. Results: 318 DRs and 77 RTTs participated. Priority areas for development included quality assurance, clinical audit, radiation dose optimisation, and improved workflow for DRs and treatment planning algorithm optimisation, clinical audit, and post processing for RTTs. There was resistance regarding AI use for patient facing roles and final image interpretation. 27.6% of DRs and 40.3% of RTTs currently use AI clinically and 46.1% of DRs and 41.2% of RTTs anticipate reduced staffing levels with AI. 64.9% of DRs and 70.6% of RTTs felt AI will be positive for patients, with the majority promoting AI regulation through national legislation. 86.1% of DRs and 94.0% of RTTs were favourable to AI implementation. Conclusion: This research identifies priority AI development and implementation areas for DRs and RTTs. It thus highlights that DRs and RTTs should be involved in development of AI tools that would best support practice, and that clearly defined pathways for AI implementation into these key professions requires discussion so that optimum use and patient safety can ensue. Implications for practice: Understanding opinions of AI has significant implications for practice, for ensuring optimal product development, implementation, and training, together with planning for potential DR and RTT role changes

Comparison of the prognostic value of ECOG-PS, MGPS and BMI/WL: Implications for a clinically important framework in the assessment and treatment of advanced cancer

BACKGROUND AND AIMS:The systemic inflammatory response is associated with the loss of lean tissue, anorexia, weakness, fatigue and reduced survival in patients with advanced cancer and therefore is important in the definition of cancer cachexia. The aim of the present study was to carry out a direct comparison of the prognostic value of Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic Score (mGPS) and Body Mass Index/Weight Loss Grade (BMI/WL grade) in patients with advanced cancer. METHOD:All data were collected prospectively across 18 sites in the UK and Ireland. Patient's age, sex, ECOG-PS, mGPS and BMI/WL grade were recorded, as were details of underlying disease including metastases. Survival data were analysed using univariate and multivariate Cox regression. RESULTS:A total of 730 patients were assessed. The majority of patients were male (53%), over 65 years of age (56%), had an ECOG-PS&gt;0/1 (56%), mGPS≥1 (56%), BMI≥25 (51%), &lt;2.5% weight loss (57%) and had metastatic disease (86%). On multivariate cox regression analysis ECOG-PS (HR 1.61 95%CI 1.42-1.83, p &lt; 0.001), mGPS (HR 1.53, 95%CI 1.39-1.69, p &lt; 0.001) and BMI/WL grade (HR 1.41, 95%CI 1.25-1.60, p &lt; 0.001) remained independently associated with overall survival. In patients with a BMI/WL grade 0/1 both ECOG and mGPS remained independently associated with overall survival. CONCLUSION:The ECOG/mGPS framework may form the basis of risk stratification of survival in patients with advanced cancer

Within-home versus between-home variability of house dust endotoxin in a birth cohort

Endotoxin exposure has been proposed as an environmental determinant of allergen responses in children. To better understand the implications of using a single measurement of house dust endotoxin to characterize exposure in the first year of life, we evaluated room-specific within-home and between-home variability in dust endotoxin obtained from 470 households in Boston, Massachusetts. Homes were sampled up to two times over 5–11 months. We analyzed 1,287 dust samples from the kitchen, family room, and baby’s bedroom for endotoxin. We fit a mixed-effects model to estimate mean levels and the variation of endotoxin between homes, between rooms, and between sampling times. Endotoxin ranged from 2 to 1,945 units per milligram of dust. Levels were highest during summer and lowest in the winter. Mean endotoxin levels varied significantly from room to room. Cross-sectionally, endotoxin was moderately correlated between family room and bedroom floor (r = 0.30), between family room and kitchen (r = 0.32), and between kitchen and bedroom (r = 0.42). Adjusting for season, the correlation of endotoxin levels within homes over time was 0.65 for both the bedroom and kitchen and 0.54 for the family room. The temporal within-home variance of endotoxin was lowest for bedroom floor samples and highest for kitchen samples. Between-home variance was lowest in the family room and highest for kitchen samples. Adjusting for season, within-home variation was less than between-home variation for all three rooms. These results suggest that room-to-room and home-to-home differences in endotoxin influence the total variability more than factors affecting endotoxin levels within a room over time

Environmental Organochlorines and Semen Quality: Results of a Pilot Study

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p'-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p'-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p'-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p'-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p'-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress

Are CT-derived muscle measurements prognostic, independent of systemic inflammation in good performance status patients with advanced cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p &lt; 0.05) and mGPS (p &lt; 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p &lt; 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p &lt; 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer

Lactate dehydrogenase: Relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer

Background: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011–2016, was retrospectively analysed. LDH values were grouped as &lt;250/250–500/&gt;500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. Results: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH &gt; 500 Units/L. LDH was significantly associated with ECOG-PS (p &lt; 0.001), NLR (p &lt; 0.05), mGPS (p &lt; 0.05) and 3-month survival (p &lt; 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p &lt; 0.01), BMI (p &lt; 0.05), skeletal muscle mass (p &lt; 0.01), metastatic disease (p &lt; 0.05), NLR (p &lt; 0.05) and mGPS (p &lt; 0.01). Discussion: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia

The relationship between the BMI-adjusted weight loss grading system and quality of life in patients with incurable cancer

Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)-adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer. A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI-adjusted WLGS into one of five distinct WL grades (grades 0-4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. The Kruskal-Wallis test and multivariate logistic regression analyses were used to assess the relationship between the WLGS and QoL scores. Overall survival was assessed using Kaplan-Meier curve and Cox proportional hazard models. A total of 1027 patients were assessed (51% male, median age: 66 years). Gastrointestinal cancer was most prevalent (40%), and 87% of patients had metastatic disease. Half (58%) of patients had a WL grade of 0-1, while 12%, 20%, and 10% had WL grades of 2, 3, and 4, respectively. Increasing WL grades were significantly associated with poorer QoL functioning and symptoms scales (all P &lt; 0.05). Physical, role, and emotional functioning decreased by a median of &gt;20 points between WL grade 0 and WL grade 4, while appetite loss, pain, dyspnoea, and fatigue increased by a median score &gt;20 points, indicative of a large clinical significant difference. Increasing WL grades were associated with deteriorating QoL summary score. WL grades 2, 3, and 4 were independently associated with a QoL summary score below the median (&lt;77.7) [odds ratio (OR) 1.69, P = 0.034; OR 2.06, P = 0.001; OR 4.29, P &lt; 0.001, respectively]. WL grades 3 and 4 were independently associated with reduced overall survival [hazard ratio 1.54 (95% confidence interval: 1.22-1.93), P &lt; 0.001 and hazard ratio 1.87 (95% confidence interval: 1.42-2.45), P &lt; 0.001, respectively]. Our findings support that the WLGS is useful in identifying patients at risk of poor QoL that deteriorates with increasing WL grades. WL grade 4 is independently associated with a particularly worse prognosis and increased symptom burden. Identification and early referral to palliative care services may benefit these patients