The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in the regulation and maintenance of bone marrow-derived multipotent stromal cells (BMSCs) that contribute to wound healing, particularly in diabetes. Through comparison of BMSCs from wild-type and diabetic mice, with a known redox and metabolic disorder, we found that the cytoprotective nuclear factor erythroid-related factor 2 (Nrf2)/kelch-like erythroid cellderived protein 1 (Keap1) pathway is dysregulated and functionally insufficient in diabetic BMSCs (dBMSCs). Nrf2 is basally active, but in chronic ROS, we found irregular inhibition of Nrf2 by Keap1, altered metabolism, and limited BMSC multipotency. Forced upregulation of Nrf2-directed transcription, through knockdown of Keap1, restores redox homeostasis. Normalized Nrf2/ Keap1 signaling restores multipotent cell properties in dBMSCs through Sox2 expression. These restored BMSCs can resume their role in regenerative tissue repair and promote healing of diabetic wounds. Knowledge of diabetes and hyperglycemia-induced deficits in BMSC regulation, and strategies to reverse them, offers translational promise. Our study establishes Nrf2/Keap1 as a cytoprotective pathway, as well as a metabolic rheostat, that affects cell maintenance and differentiation switches in BMSCs.

Background The effects of the coronavirus disease 2019 (COVID‐19) pandemic on surgical oncology practice are not yet quantified. The aim of this study was to measure the immediate impact of COVID‐19 on surgical oncology practice volume. Methods A retrospective study of patients treated at an NCI‐Comprehensive Cancer Center was performed. “Pre‐COVID” era was defined as January–February 2020 and “COVID” as March–April 2020. Primary outcomes were clinic visits and operative volume by surgical oncology subspecialty. Results Abouyt 907 new patient visits, 3897 follow‐up visits, and 644 operations occurred during the study period. All subspecialties experienced significant decreases in new patient visits during COVID, though soft tissue oncology (Mel/Sarc), gynecologic oncology (Gyn/Onc), and endocrine were disproportionately affected. Telehealth visits increased to 11.4% of all visits by April. Mel/Sarc, Gyn/Onc, and Breast experienced significant operative volume decreases during COVID (25.8%, p = 0.012, 43.6% p < 0.001, and 41.9%, p < 0.001, respectively), while endocrine had no change and gastrointestinal oncology had a slight increase (p = 0.823) in the number of cases performed. Conclusions The effects of the COVID‐19 pandemic are wide‐ranging within surgical oncology subspecialties. The addition of telehealth is a viable avenue for cancer patient care and should be considered in surgical oncology practice.

lymphedema. Deterioration in cosmesis ≥ 3 months after RT was seen in 1.6% of Arm A and 1.7% of Arm B (P = 0.4). The average Harvard Cosmesis score was similar between arms at all timepoints. QOL was similar between arms, as well. Patient-reported radiation skin burns of 'moderate to severe' as assessed by PRO-CTCAE were more commonly reported in Arm A (58.7%) vs Arm B (27.9%) (odds ratio 3.7, CI 1.5-8.9; P = 0.004). Patient satisfaction with treatment was very high with more than 98% of patients in both arms saying that they would do RT again. No cancer recurrences or deaths have been seen in either arm. Conclusion: Our early analysis of our randomized study suggests that extreme hypofractionation using 25 Gy in 5 fractions is well-tolerated and as safe as moderate hypofractionation. Patient-reported radiation skin burns were 3.7 times less likely with 25 Gy in 5 fractions. Further follow-up is warranted.

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