Navigating job and cancer demands during treatment: A qualitative study of ovarian cancer patients.

OBJECTIVE: Our objective was to obtain perspectives from ovarian cancer patients on job demands, cancer demands, and workplace or cancer resources and strategies to manage the cancer-work interface using the cancer-work management conceptual framework. METHODS: We recruited ovarian cancer patients receiving systemic therapy who screened positive for financial distress using Comprehensive Score for Financial Toxicity <26. Interviews were conducted with participants about their costs of care, including employment concerns. Interviews were recorded, transcribed verbatim, and analyzed by three researchers using an inductive thematic analysis. RESULTS: Of 22 participants, the average age was 57 years old, 36% were Black, 68% had income <$40,000, 41% had public insurance, and 68% were being treated for recurrent disease. Job demands included decreased productivity, inability to return to work, and worry about losing a job or employer-based health insurance coverage. Cancer demands included physical and cognitive limitations due to cancer treatment and reliance on caregivers, especially for transportation. Workplace resources/strategies including having a supportive employer, modifying job responsibilities, and utilizing family medical leave. Cancer care resources/strategies included planning appointments ahead of time and utilizing resources, such as disability. CONCLUSIONS: Cancer care teams should consider screening patients for employment concerns; streamline care to minimize the side effects, time, and transportation demands of treatment on patients and caregivers; maximize utilization of available resources; and proactively communicate with employers to accommodate patients and caregivers who want or need to work.

Evaluating meaningful levels of financial toxicity in gynecologic cancers.

OBJECTIVE: The Comprehensive Score for Financial Toxicity (COST) is a validated instrument measuring the economic burden experienced by patients with cancer. We evaluated the frequency of financial toxicity at different COST levels and stratified risk factors and associations with cost-coping strategies by financial toxicity severity. METHODS: We analyzed previously collected survey data of gynecologic oncology patients from two tertiary care institutions. Both surveys included the COST tool and questions assessing economic and behavioral cost-coping strategies. We adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity and used χ2, Fisher's exact test, and Wilcoxon rank sum test to compare groups. We used Poisson regression to calculate crude and adjusted risk ratios for cost-coping strategies, comparing patients with moderate or severe to no/mild financial toxicity. RESULTS: Among 308 patients, 14.9% had severe, 32.1% had moderate, and 52.9% had no/mild financial toxicity. Younger age, non-white race, lower education, unemployment, lower income, use of systemic therapy, and shorter time since diagnosis were associated with worse financial toxicity (all p<0.05). Respondents with moderate or severe financial toxicity were significantly more likely to use economic cost-coping strategies such as changing spending habits (adjusted risk ratio (aRR) 2.7, 95% CI 1.8 to 4.0 moderate; aRR 3.6, 95% CI 2.4 to 5.4 severe) and borrowing money (aRR 5.5, 95% CI 1.8 to 16.5 moderate; aRR 12.7, 95% CI 4.3 to 37.1 severe). Those with severe financial toxicity also had a significantly higher risk of behavioral cost-coping through medication non-compliance (aRR 4.6, 95% CI 1.2 to 18.1). CONCLUSIONS: Among a geographically diverse cohort of gynecologic oncology patients, nearly half reported financial toxicity (COST <26), which was associated with economic cost-coping strategies. In those 14.9% of patients reporting severe financial toxicity (COST <14) there was also an increased risk of medication non-compliance, which may lead to worse health outcomes in this group.

Investigation of racial disparities in semen parameters among white, black, and Asian men.

BACKGROUND: Male factor infertility is the primary cause of infertility in 20% of couples. Primary evaluation of male factor infertility includes a semen analysis (SA). The World Health Organization (WHO) criteria are widely used to interpret SA. However, the current normative values seen in WHO criteria have led to research showing racial disparities in prevalence of abnormal SA. OBJECTIVE: To assess the relationship between different self-reported racial groups and rates of abnormal SA. MATERIALS & METHODS: We conducted a retrospective cohort study at a single large tertiary care facility. All men who underwent a SA for evaluation of suspected male infertility, unexplained infertility, intrauterine insemination, and in vitro fertilization between January 1, 2017 and December 31, 2019, were considered for inclusion in the study. Exclusion criteria were unreported race or ethnicity, SA for fertility preservation only, history of varicocele or testicular surgery, chromosomal abnormalities, congenital bilateral absence of vas deferens, prior testosterone use, or prior exposure to chemotherapy and/or radiation. Samples obtained via testicular sperm extraction or post-ejaculatory urine collection, or those analyzed ≥1 h from ejaculation, were also excluded. RESULTS: 872 SAs were identified, of which 615 met inclusion criteria, yielding 384 normal and 231 abnormal results. Only race (p < 0.0001) and age (p = 0.002) were statistically significant. Black men had the highest rate of abnormal SA (54%) and were significantly more likely to have lower semen volume, sperm concentration, total sperm count, percent motile sperm, and total motile sperm (p < 0.05). In a logistic regression model, controlling for age and using White Non-Hispanic as the referent group, only Blacks had lower odds for a normal SA (OR = 0.41, 95% CI 0.28, 0.60). DISCUSSION AND CONCLUSIONS: Black men are more likely to have an abnormal SA based on the 2010 WHO criteria. Black men seeking infertility treatment should be educated on the incidence of abnormal SA and actively seek infertility evaluation.

ASC spheroid geometry and culture oxygenation differentially impact induction of preangiogenic behaviors in endothelial cells.

Cell-based angiogenic therapies offer potential for the repair of ischemic injuries, while avoiding several of the limitations associated with material-based growth factor delivery strategies. Evidence supports that applying MSCs as spheroids rather than dispersed cells can improve retention and enhance therapeutic effect through increased secretion of angiogenic factors due to hypoxia. However, while spheroid culture appears to modulate MSC behavior, there has been little investigation of how major culture parameters that affect cellular oxygen tension, such as external oxygenation and culture size, impact the angiogenic potential of spheroids. We cultured equal numbers of adipose-derived stem cells (ASCs) as spheroids containing 10,000 (10k) or 60,000 (60k) cells each, in 20% and 2% oxygen. VEGF secretion varied among the sample groups, with 10k, 2% O2 spheroids exhibiting the highest production. Spheroid-conditioned media was applied to HUVEC monolayers, and proliferation was assessed. Spheroids of either size in 2% oxygen induced comparable proliferation compared to a 2 ng/ml VEGF control sample, while spheroids in 20% oxygen induced less proliferation. Spheroids were also applied in coculture with HUVEC monolayers, and induction of migration through a Transwell membrane was evaluated. Sixty thousand, 2% O2 spheroids induced similar levels of migration as VEGF controls, while 10k, 2% O2 spheroids induced significantly more. Ten thousand, 20% spheroids performed no better than VEGF-free controls. We conclude that the therapeutic ability of ASC spheroids to stimulate angiogenesis in endothelial cells is affected by both culture size and oxygenation parameters, suggesting that, while ASC spheroids offer potential in the treatment of injured and ischemic tissues, careful consideration of culture size in respect to in vivo local oxygen tension will be necessary for optimal results.

Use of culture geometry to control hypoxia-induced vascular endothelial growth factor secretion from adipose-derived stem cells: optimizing a cell-based approach to drive vascular growth.

Adipose-derived stem cells (ADSCs) possess potent angiogenic properties and represent a source for cell-based approaches to delivery of bioactive factors to drive vascularization of tissues. Hypoxic signaling appears to be largely responsible for triggering release of these angiogenic cytokines, including vascular endothelial growth factor (VEGF). Three-dimensional (3D) culture may promote activation of hypoxia-induced pathways, and has furthermore been shown to enhance cell survival by promoting cell-cell interactions while increasing angiogenic potential. However, the development of hypoxia within ADSC spheroids is difficult to characterize. In the present study, we investigated the impact of spheroid size on hypoxia-inducible transcription factor (HIF)-1 activity in spheroid cultures under atmospheric and physiological oxygen conditions using a fluorescent marker. Hypoxia could be induced and modulated by controlling the size of the spheroid; HIF-1 activity increased with spheroid size and with decreasing external oxygen concentration. Furthermore, VEGF secretion was impacted by the hypoxic status of the culture, increasing with elevated HIF-1 activity, up to the point at which viability was compromised. Together, these results suggest the ability to use 3D culture geometry as a means to control output of angiogenic factors from ADSCs, and imply that at a particular environmental oxygen concentration an optimal culture size for cytokine production exists. Consideration of culture geometry and microenvironmental conditions at the implantation site will be important for successful realization of ADSCs as a pro-angiogenic therapy.