Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study.

Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders.Results: Of 12,572 PDAC patients, 950 (7.56%) had used metformin alone, 4,506 (35.84%) had used statin alone, and 2,445 (19.45%) were dual users. Statin use was significantly associated with improved overall survival [HR, 0.94; 95% confidence interval (CI), 0.90-0.98], and survival was more pronounced in postdiagnosis statin users (HR, 0.69; 95% CI, 0.56-0.86). Metformin use was not significantly associated with overall survival (HR, 1.01; 95% CI, 0.94-1.09). No beneficial effect was observed for dual users (HR, 1.00; 95% CI, 0.95-1.05).Conclusions: Our findings suggest potential benefits of statins on improving survival among elderly PDAC patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer.Impact: Although more studies are needed to confirm our findings, our data add to the body of evidence on potential anticancer effects of statins. Cancer Epidemiol Biomarkers Prev; 26(8); 1225-32. ©2017 AACR

Natural Experiment Examining Impact of Aggressive Screening and Treatment on Prostate Cancer Mortality in Two Fixed Cohorts from Seattle Area and Connecticut

To determine whether the more intensive screening and treatment for prostate cancer in the Seattle≠Puget Sound area in 1987≠90 led to lower mortality from prostate cancer than in Connecticut

Longitudinal Associations of Leisure-Time Physical Activity and Cancer Mortality in the Third National Health and Nutrition Examination Survey (1986–2006)

Longitudinal associations between leisure-time physical activity (LTPA) and overall cancer mortality were evaluated within the Third National Health and Nutrition Examination Survey (NHANES III; 1988–2006; n = 15,535). Mortality status was ascertained using the National Death Index. Self-reported LTPA was divided into inactive, regular low-to-moderate and vigorous activity. A frequency-weighted metabolic equivalents (METS/week) variable was also computed. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated for overall cancer mortality in the whole sample, by body mass index categories and insulin resistance (IR) status. Nonsignificant protective associations were observed for regular low-to-moderate and vigorous activity, and for the highest quartile of METS/week (HRs range: 0.66–0.95). Individuals without IR engaging in regular vigorous activity had a 48% decreased risk of cancer mortality (HR: 0.52; 95% CI: 0.28–0.98) in multivariate analyses. Conversely, nonsignificant positive associations were observed in people with IR. In conclusion, regular vigorous activity may reduce risk of cancer mortality among persons with normal insulin-glucose metabolism in this national sample

Racial Disparities in Diabetes Mellitus Prevalence in Prostate Cancer Patients on Androgen Deprivation Therapy

Intro/Background Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostate cancer. ADT has show to prolong survival. The use of ADT is associated with many side effects, most notably an increase in diabetes incidence for patients on ADT. African American men have higher prevalence and mortality rates from prostate cancer than White men. It is unclear how prostate cancer treatment such as ADT affects these disparities. This study examines racial differences in the prevalence of diabetes mellitus in prostate cancer patients based on their ADT status in the US.https://jdc.jefferson.edu/medoncposters/1016/thumbnail.jp

A Scoping Review Protocol to Elucidate Outcomes Following Abiraterone Versus Enzalutamide for Prostate Cancer

INTRODUCTION: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, and clinical decision making. METHOD AND ANALYSIS: The framework for this methodology was informed by the Joanna Briggs Institute methodology for scoping reviews. Title and abstract screening will be performed by two independent researchers to create an initial study inventory. This will be followed by full-text screening for study inclusion. Population-based studies describing patient outcomes, common toxicities, and associations with patient co-morbidities following abiraterone or enzalutamide therapy will be included. After data is extracted, it will be summarized for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors informing treatment choice between abiraterone and enzalutamide for castration-resistant prostate cancer. All data are from published openly accessible sources, and therefore, no ethical clearance is necessary. The protocol is also registered at https://doi.org/10.6084/m9.figshare.19149227

Epigenetic Dysregulations in Arsenic-Induced Carcinogenesis

Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced epigenetic modifications in carcinogenesis and angiogenesis. Importantly, we highlight the possible mechanisms underlying epigenetic reprogramming through arsenic exposure that cause changes in cell signaling and dysfunctions of different epigenetic elements

Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen deprivation therapy. This review aims to present the current research on androgen deprivation therapy and cardiovascular toxicity with an emphasis on racial disparities and provides a framework for clinicians to decrease the cardiovascular morbidity in men that are being treated with hormone therapy

CFD investigation of gas-solids flow in a new fluidized catalyst cooler

In our previous work, a new concept of annular catalyst cooler (ACC) was proposed and validated experimentally, which showed that an internal circulation of solids could be formed by using two gas distributors and both hydrodynamics and heat transfer could be largely improved. The current work simulated detailed hydrodynamics of gas-solids flow to advance our understanding of the ACC by using the two-fluid model. The influences of effective particle diameter dp⁎ and specularity coefficient φ were examined and compared with experimental data. Optimum values of dp⁎ = 170 μm and φ = 0.3 were determined and used in the simulations. Detailed hydrodynamics of gas-solids flow were then obtained, and the influential parameters were examined. The results showed that the proper selection of the ratio of gas velocities and the position of the heat transfer tube were needed to form a stable internal solids circulation in the ACC. The ACC had a combined hydrodynamic feature of up-flow and down-flow catalyst coolers with bigger solids volume fraction and smaller particle resident time, which are beneficial for improving the heat transfer between solids and wall

Is Timing of Steroid Exposure Prior to Immune Checkpoint Inhibitor Initiation Associated with Treatment Outcomes in Melanoma? A Population-Based Study

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1–3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65–3.08; and HR: 1.51, 95% CI: 1.01–2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids