Urinary Bladder Matrix Improves Irradiated Wound Healing in a Murine Model.

ABSTRACT: Radiation skin damage is associated with chronic wounds and poor healing. Existing localized treatment modalities have limited benefit. Therefore, there has been increased interest in biologically based solutions. In this study, we aimed to determine the effect of topical urinary bladder matrix (UBM) on chronic irradiated skin wounds using an established murine model. Our findings demonstrated that topical urinary bladder matrix significantly accelerated the healing of irradiated wounds on day 7 (P = 0.0216), day 14 (P = 0.0140), and day 21 (P = 0.0393). Histologically, urinary bladder matrix treatment was associated with higher-quality reorganization and reepithelialization of wounds, an increased density of myofibroblasts (P = 0.0004), and increased collagen deposition (P < 0.0001). In addition, quantitative real-time polymerase chain reaction data demonstrated decreased expression of profibrotic mediators (P = 0.0049). We conclude that urinary bladder matrix may be a useful, noninvasive, adjunctive therapy for the treatment of chronic irradiated skin wounds.

Patient Characteristics Associated with Free Nipple Graft Reduction Mammoplasty.

PURPOSE: Surgical approaches for reduction mammoplasty most commonly incorporate a parenchymal vascular pedicle. For patients with larger breasts where pedicle viability may be compromised due to excessive length, the free nipple graft (FNG) technique provides a safe alternative. Criteria for whether a patient should undergo a FNG remains controversial due to variable reports in the literature with small sample sizes and inherent surgeon-dependent bias. To address this, we sought to investigate perioperative factors associated with performing FNGs at our institution in order to better elucidate specific indications for this surgery. METHODS: A retrospective chart review was performed for 323 patients who underwent a reduction mammoplasty from August 2009 to July 2019 at Keck Hospital and LAC+USC Medical Center. Data regarding patient demographics, comorbidities, pre-operative breast characteristics, and post-operative complications were extracted. Student's t-test, Fisher's exact test, and logistic regression were performed in R. RESULTS: Of 323 patients, 15 received an FNG. Independent variables analyzed included: age, body mass index (BMI), obesity, smoking, diabetes, hypertension, surgical indication, sternal notch-to-nipple length, nipple-to-inframammary fold length, and weight of breast specimens removed. BMI, obesity, gigantomastia, and weight of specimen resected were significantly associated with use of the FNG (p < 0.001, p < 0.05, p < 0.0001, p < 0.0001, respectively). Regression analysis revealed that patients who had an average of more than 1500 g of tissue removed from each breast were 1.41 (95% CI: 1.17-1.71, p<0.001) times more likely to undergo an FNG procedure than those who had less than 1500 g of tissue removed. Demographic data and breast characteristics, such as notch-to-nipple length and nipple-to-inframammary fold length, were not significantly associated. CONCLUSION: Total weight of the breast specimens removed and BMI were significantly associated with the FNG technique. Removing more than 1500 g gof total breast tissue was also significantly correlated. These findings may guide surgeons during the decision-making process of when to use an FNG.

Glycolysis and glutaminolysis cooperatively control T cell function by limiting metabolite supply to N-glycosylation.

Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans. Here, we report that aerobic glycolysis and glutaminolysis co-operatively reduce UDP-GlcNAc biosynthesis and N-glycan branching in mouse T cell blasts by starving the hexosamine pathway of glucose and glutamine. This drives growth and pro-inflammatory TH17 over anti-inflammatory-induced T regulatory (iTreg) differentiation, the latter by promoting endocytic loss of IL-2 receptor-α (CD25). Thus, a primary function of aerobic glycolysis and glutaminolysis is to co-operatively limit metabolite supply to N-glycan biosynthesis, an activity with widespread implications for autoimmunity and cancer.