Long-term Survival Outcomes for Men Who Provided Ejaculate Specimens for Prostate Cancer Research: Implications for Patient Management

Background: Determining whether men diagnosed with early prostate cancer (PCa) will live long enough to benefit from interventions with curative intent is difficult. Although validated instruments for predicting patient survival are available, these do not have clinical utility so are not used routinely in practice. Objective: To test the hypothesis that volunteers who provided ejaculate specimens had a high survival rate at 10 and 15 yr and beyond. Design, setting, and participants: A total of 290 patients investigated because of high serum prostate-specific antigen donated ejaculate specimens for research between January 1992 and May 2003. The median age at the time of ejaculation was 63.5 yr. 153 of the donors were diagnosed with PCa and followed up to December 31, 2013. Outcome measurements and statistical analysis: Survival outcomes were compared with those for the whole population, as indicated by life expectancy tables up to 20 yr. Results and limitations: Men in the PCa group had life expectancies comparable with values listed in life expectancy tables for the whole population. Overall, PCa-specific and relative survival were significantly better for men in the non-PCa and PCa groups in comparison with men diagnosed with PCa in Queensland during the same period. Relative survival for those aged 20-49, 50-64, and ≥65 yr was >100% for ejaculate donors and 81.5%, 82.7%, and 65.2%, respectively, for the Queensland Cancer Registry reference at 10 yr. These findings for this highly selected patient cohort support the hypothesis that an ability to provide an ejaculate specimen is associated with a high likelihood of surviving 10-20 yr after donation, whether or not PCa was detected. Conclusion: Life expectancy tables may serve as a quick and simple life expectancy indicator for biopsy patients who donate ejaculate. Patient summary: Life expectancy tables indicated survival of up to 20 yr for men who provided ejaculate specimens for prostate cancer research. Life expectancy tables indicated survival of up to 20 yr for men who provided ejaculate specimens for prostate cancer research

Seminal plasma enables selection and monitoring of active surveillance candidates using nuclear magnetic resonance-based metabolomics: A preliminary investigation

Background: Diagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort. Materials and methods: Seminal plasma samples of 151 men being investigated for prostate cancer were analyzed with 1H-NMR spectroscopy. After adjustment for buffer (add-to-subtract) and endogenous enzyme influence on metabolites, metabolite profiling was performed with multivariate statistical analysis (principal components analysis, partial least squares) and targeted quantitation. Results: Seminal plasma metabolites best predicted low- and intermediate-risk prostate cancer with differences observed between these groups and benign samples. Lipids/lipoproteins dominated spectra of high grade samples with less metabolite contributions. Overall prostate cancer prediction using previously described metabolites was not validated. Conclusion: Metabolomics of seminal plasma in vitro may assist urologists with diagnosis and monitoring of either low or intermediate grade prostate cancer. Less clinical benefit may be observed for high-risk patients. Further investigation in active surveillance cohorts, and/or in combination with in vivo magnetic resonance spectroscopic imaging may further optimize localized prostate cancer outcomes

Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers

Background Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers. Methods Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D\u27Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis. Results From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size. Conclusion PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination–urine markers

Measurement of SARS-CoV-2 in air and on surfaces in Scottish hospitals

BackgroundThere are still uncertainties in our knowledge of the amount of SARS-CoV-2 virus present in the environment; where it can be found, and potential exposure determinants, limiting our ability to effectively model and compare interventions for risk management.AimThis study measured SARS-CoV-2 in three hospitals in Scotland on surfaces and air, alongside ventilation and patient care activities.MethodsAir sampling at 200 L/min for 20 minutes and surface sampling were performed in two wards designated to treat COVID-19 -positive patients and two non-COVID-19 wards across three hospitals in November and December 2020. FindingsDetectable samples of SARS-CoV-2 were found in COVID-19 treatment wards but not in non-COVID-19 wards. Most samples were below assay detection limits, but maximum concentrations reached 1.7x10 3 genomic copies/m3 in air and 1.9x10 4 copies per surface swab (3.2x10 2 copies/cm2 for surface loading). The estimated geometric mean air concentration (geometric standard deviation) across all hospitals was 0.41 (71) genomic copies/m3 and the corresponding values for surface contamination were 2.9 (29) copies/swab. SARS-CoV-2 RNA was found in non-patient areas (patient/visitor waiting rooms and personal protective equipment (PPE) changing areas) associated with COVID-19 treatment wards.ConclusionsNon-patient areas of the hospital may pose risks for infection transmission and further attention should be paid to these areas. Standardization of sampling methods will improve understanding of levels of environmental contamination. The pandemic has demonstrated a need to review and act upon the challenges of older hospital buildings meeting current ventilation guidance

A Cost-Utility Analysis of Prostate Cancer Screening in Australia

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92$AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically

The effect of subduction on the sulphur, carbon and redox budget of lithospheric mantle

Subduction of hydrated lithospheric mantle introduces H O, ferric iron, oxidized carbon and sulphur to the subduction zone system. The fate of these components is poorly known, but is intimately linked to the global geochemical cycles of iron, carbon and sulphur, the genesis of arc-related ore deposits, the temporal evolution of mantle redox state and subduction-related earthquakes and magmatism. thermocalc is used to provide first-order constraints on the effect of subduction zone metamorphism on metamorphic redistribution of iron, carbon, sulphur and water in ultramafic rocks via construction of P−T and T-X(O) pseudosections with open system calculation of the effect of fluid loss. The calculations replicate observed mineral assemblages in high-P to low-T ultramafic rocks at P−T conditions consistent with those suggested by other workers. The results are consistent with open system fluid loss without significant fluid infiltration. Water loss is complete by 850 C, the corresponding depth of fluid loss being consistent with that inferred for earthquakes in subducting slabs. Losses of carbon and sulphur are relatively minor, at around 5 GPa, below the depths of the source zone for arc volcanoes.Oxygen activity for rocks in closed systems that evolve with a fixed redox budget is calculated to change from ΔFMQ −1 at 350 C to over ΔFMQ +3 at 850 C. This result emphasizes the need to consider redox budget as well as oxygen activity when the results of experiments performed at fixed oxygen activity relative to some buffer are interpreted in the context of natural systems. In open systems, devolatilization is calculated to increase the redox budget and oxygen activity of the residue via loss of methane and H S at the brucite-out and serpentine-out reactions respectively. No fluid-induced mechanism for oxidation of sub-arc mantle by transfer of redox budget from hydrated ultramafic lithologies to the overlying sub-arc mantle was identified, although further thermodynamic data on fluid species such as S are required to confirm this

Prostate cancer: active surveillance as a management option

Background Active surveillance, followed by delayed definitive treatment for those who develop evidence of significant cancer progression, is now a recognised management strategy for selected men with low risk prostate cancer. Objective This article summarises the role of active surveillance in the management of prostate cancer. It outlines the benefits of active surveillance and the indications for proceeding with curative treatments if required. Discussion A considerable proportion of men with low grade prostate cancer on biopsy may never progress to higher stage disease or develop symptoms from their cancers. These patients are suitable for active surveillance under the care of a urologist. Active surveillance involves initial stringent observation of the prostate cancer, with inclusion of monitoring biopsies rather than immediate active treatment in the form of surgery or radiotherapy. With careful selection, about 70% of men will not require any intervention for at least 5 years. Men with low grade disease should be offered active surveillance as a treatment option and provided with information about the risks and benefits of this approach