Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Economic Outcomes of Hexaminolevulinate Blue-Light Cystoscopy in Non-Muscle Invasive Bladder Cancer: A 5-Year, Medicare-Based Model.

BACKGROUND: Bladder cancer is the most expensive cancer to treat on a per-patient basis. Blue light cystoscopy with hexaminolevulinate (BLC) has demonstrated improved diagnostic accuracy compared with white light cystoscopy (WLC) in non-muscle invasive bladder cancer (NMIBC). With higher upfront costs, questions remain about long-term BLC cost outcomes. OBJECTIVE: This study seeks to investigate the 5-year cost comparison of BLC and WLC from the Medicare payer perspective. METHODS: A representative 5-year NMIBC management model was constructed and Medicare reimbursement values were overlaid. The primary outcome was mean year-over-year cumulative cost discounted to present value at a 3% annual percentage rate. The secondary outcome was the rate of clinical events. RESULTS: Patients in the BLC cohort experienced fewer recurrences. On a cumulative present value cost basis, BLC was more expensive per patient in years 1, 2, and 3 than WLC, however, in years 4 and 5, BLC was economically favorable. Year 5 BLC mean cumulative cost savings was $1,172 per patient. Overall, 31.6% of all patients in the BLC group generated cumulative cost savings compared to WLC at year 1 compared with 50.9% at the end of year 5. CONCLUSIONS: Despite a higher initial annual cost, a slight cumulative economic advantage of BLC is realized after surveillance year 3. Additionally, a greater proportion of patients who received BLC achieved cost savings at the end of year 5. As novel technology emerges, economic models can help health care systems predict associated costs and quality improvements.

Patient-Reported Financial Burden Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer.

Introduction and Objectives: In patients with localized prostate cancer, 5-fraction, stereotactic body radiation therapy (SBRT) has been found to offer comparable oncologic outcomes and potential for improved treatment compliance compared to conventional, 40-plus fraction radiation therapy (RT). Recent studies of oncologic patient experiences have highlighted both the impact of therapy-associated financial toxicity (FT) on treatment adherence and health-related quality of life (HRQOL). Methods: A cross-sectional assessment of FT after SBRT was performed using the 12-item COST questionnaire. The total questionnaire score (range 0-44) was used to evaluate the FT grade (0-3), with a higher COST value representing lower grade. The patient zip code was used to approximate the distance from the index hospital. Univariate and multivariate analyses of the average COST score (0-4) are performed. Results: The response rate was 57.5% (332 of 575 consented patients) with 90.7%, 8.2%, and 1.1% experiencing grade 0, 1, and 2 FT, respectively, with no grade 3. Unemployment or disability, non-white race, low income, and concurrent hormonal therapy were associated with a statistically significant worse FT (lower COST value) on univariate and multivariate analyses (p < 0.05). Education level and insurance status significant were evaluated on univariate analysis only. There was a non-statistically significant difference in age, marital status, time since treatment, and distance from the index hospital. Conclusions: SBRT was associated with low FT. However, statistically significant socioeconomic disparities in FT remain despite ultra-hypofractionated treatment.

Giant primary vaginal tubulovillous adenoma: A case report and review of literature.

Primary adenomas are common in the gastrointestinal tract but exceedingly rare on the periurethral surface and vagina. The pathogenesis remains unknown but vaginal adenomas are hypothesized to arise from vaginal adenosis or embryonic cloacal remnants and possess malignant potential. We present a case of a large primary vaginal tubulovillous adenoma in an eighty-one-year-old, likely diethylstilbestrol naïve patient. To the best of our knowledge the patient's 7.4 x 4.5 × 1.4 cm primary vaginal tubulovillous adenoma is the largest ever reported in literature.

Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy.

Lymph node recurrent prostate cancer is a common clinical scenario that is likely to increase significantly with the widespread adoption of novel positron emission tomography (PET) agents. Despite increasing evidence that localized therapy is disease modifying, most men with lymph node recurrent prostate cancer receive only systemic therapy with androgen deprivation therapy (ADT). For men who receive localized therapy the intent is often to delay receipt of systemic therapy. Little evidence exists on the optimal combination of local and systemic therapy in this patient population. In this hypothesis generating review, we will outline the rationale and propose a framework for combining involved field SBRT with risk adapted intermittent ADT for hormone sensitive nodal recurrent prostate cancer. In patients with a limited number of nodal metastases, involved field stereotactic body radiation therapy (SBRT) may have a role in eliminating castrate-resistant clones and possibly prolonging the response to intermittent ADT. We hypothesize that in a small percentage of patients, such a treatment approach may lead to long term remission or cure.