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Study Objective: To compare preoperative femoral (FNB) with combined femoral and sciatic nerve block (CFSNB) in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction.Design: Prospective, randomized clinical trial.Setting: Ambulatory surgery center affiliated with an academic medical center.Patients: Sixty-eight American Society of Anesthesiology physical status I and II patients undergoing arthroscopic ACL reconstruction.Interventions: Subjects randomized to the CFSNB group received combined femoral and sciatic nerve blocks preoperatively, whereas patients randomized to the FNB group only received femoral nerve block preoperatively. Both groups then received a standardized general anesthetic with a propofol induction followed by sevoflurane or desflurane maintenance. Intraoperative pain was treated with fentanyl. Pain in the postanesthesia care unit (PACU) was treated with ketorolac and opiates. Patients with significant pain despite ketorolac and opiates could receive a rescue nerve block.Measurements: Our primary outcome variable was highest Numeric Rating Scale (NRS) pain score in PACU. NRS pain scores, opioid consumption, opioid adverse effects, and patient satisfaction were assessed perioperatively until postoperative day 3.Main Results: The highest PACU NRS pain score was significantly higher in the FNB group compared with the CFSNB group (7 [3-10] vs 5 [0-10], P=.002). The FNB group required significantly larger doses of opioids perioperatively (31.8 vs 19.8mg intravenous morphine equivalents, P<.001). PACU length of stay was significantly longer in the FNB group (128.2 vs 103.1minutes, P=.006). There was no significant difference in opioid consumption, pain scores, or patient satisfaction on postoperative days 1-3 between groups.Conclusions: Preoperative CFSNB for arthroscopic ACL reconstruction improves analgesia, decreases opioid consumption perioperatively, and decreases PACU length of stay when compared with FNB alone. [ABSTRACT FROM AUTHOR]

Aims: Though unmitigated oxidative stress in diabetic chronic non-healing wounds poses a major therapeutic challenge, currently, there are no effective pharmacological agents. We targeted the cytoprotective Nrf2/Keap1 pathway, which is dysfunctional in diabetic skin and the regenerative environment in the diabetic wound. We assessed the efficacy of a potent Nrf2-activator, RTA 408, a semi-synthetic oleanane triterpenoid, on accelerating diabetic wound healing.Methods: Using Leprdb/dbmice, we made 10 mm-diameter excisional humanized wounds in dorsal skin. We administered RTA 408 formulations daily, and used ANOVA for comparison of time to closure, in vivo real-time ROS, histology, molecular changes.Results: We found that RTA 408, specifically a 0.1% formulation, significantly reduced wound healing time and increased wound closure rate. While either systemic or topical administration of RTA 408 is effective, wound closure time with the latter was far superior. RTA 408-treated diabetic wounds upregulated Nrf2 and downstream antioxidant genes, and exhibited well-vascularized granulation tissue that aided in re-epithelialization. Reintroduction of redox mechanisms via RTA 408-induced Nrf2 resulted in reduction of the oxidative status of wounds, to coordinate successful wound closure.Conclusions: This preclinical study shows that promoting Nrf2-mediated antioxidant activity in the localized regenerative milieu of a diabetic wound markedly improves the molecular and cellular composition of diabetic wound beds. RTA 408 treats and corrects the irregularity in redox balance mechanisms involving Nrf2, in an avenue not explored previously for treatment of diabetic wounds and tissue regeneration. Our study supports development of RTA 408 as a therapeutic modality for chronic diabetic wounds. [ABSTRACT FROM AUTHOR]