Effects of exercise dose and type during breast cancer chemotherapy on longer-term patient-reported outcomes and health-related fitness: A randomized controlled trial

The Combined Aerobic and Resistance Exercise (CARE) Trial compared different types and doses of exercise performed during breast cancer chemotherapy. Here, we report the longer-term follow-up of patient-reported outcomes, health-related fitness and exercise behavior at 6, 12 and 24 months postintervention. A multicenter trial in Canada randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of a standard dose of 25–30 min of aerobic exercise (STAN; n = 96), a higher dose of 50–60 min of aerobic exercise (HIGH; n = 101) or a combined dose of 50–60 min of aerobic and resistance exercise (COMB; n = 104) performed for the duration of chemotherapy (median of 17 weeks). Primary outcomes were patient-reported outcomes including quality of life, cancer-related symptoms and psychosocial outcomes. Secondary outcomes were objective health-related fitness (assessed at 12 months only) and self-reported exercise behavior. A total of 269 (89.4%) participants completed patient-reported outcomes at all three follow-up time points and 263 (87.4%) completed the health-related fitness assessment at 12-month follow-up. COMB was significantly superior to (i) STAN for sleep quality at 6-month follow-up (p = 0.027); (ii) HIGH for upper body muscular endurance at 12-month follow-up (p = 0.020); and (iii) HIGH for meeting the resistance exercise guideline at 6-month follow-up (p = 0.006). Moreover, self-reported meeting of the combined exercise guideline during follow-up was significantly associated with better patient-reported outcomes and health-related fitness. Performing combined exercise during and after breast cancer chemotherapy may result in better longer-term patient-reported outcomes and health-related fitness compared to performing aerobic exercise alone.     

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Reassessment of CD62L as a marker of pre-effector T cells in the tumor draining lymph nodes of head and neck cancer patients.

OBJECTIVES: CD62L was evaluated as a determinant of human pre-effector T cells. STUDY DESIGN AND SETTING: Phenotype and cytokine secretion profiles of CD62L cells were determined based on activation status. RESULTS: CD62L(Low) T cells demonstrated significantly higher secretion of interleukin (IL)-10 and interferon (IFN)-gamma than did CD62L(High) T cells. After activation, the majority of cells expressed high levels of the CD62L surface marker. Postactivation levels of IL-10 production remained elevated or unchanged. In a murine B16 melanoma model, freshly isolated CD62L(Low) tumor draining lymph nodes (TDLN) T cells showed increased secretion of IL-2 and IL-4 but not of IL-10 or IFN-gamma. The surface expression of CD62L and cytokine secretion patterns were maintained after activation with concomitant increases in IL-10. CONCLUSION: Our results provide evidence that CD62L(Low) T cells in TDLNs of progressively growing squamous cell carcinoma of the head and neck differ phenotypically and functionally from those of mouse origin. SIGNIFICANCE: Characterization of this human CD62L(Low) T cell population provides initial insight regarding novel surface markers in TDLN T cells that might correlate with antitumor reactivity.     

The health-related quality of life of male and female heavy smokers

Objectives: Heavy smokers are a segment of the smoking population who are at increased risk of smoking-related morbidity and least likely to achieve cessation. This study identifies the impact of heavy smoking on quality of life by gender and describes the subpopulation for improved targeting.Methods: South Australian representative population data (n = 3010) was used to compare the health-related quality of life status of male and female heavy smokers as assessed by the SF-36.     

Cryptococcal Meningitis in Patients with the Acquired Immunodeficiency Syndrome

The optimum therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS) remains unresolved. Traditional therapy consists of amphotericin B with or without flucytosine. Obstacles exist in administering these agents to patients with AIDS. Mortality rates during initial therapy are relatively high. Given the lack of proved benefit, we do not recommend adding flucytosine to amphotericin B routinely. The search for more efficacious and less toxic agents continues. The oral triazoles, especially fluconazole, have increased the options for treatment of this disease. New strategies and novel approaches in managing cryptococcal meningitis in patients with AIDS continue to be developed.