Rapid Recovery Is Feasible for Aseptic Revision Total Knee Arthroplasty at an Academic Medical Center.

BACKGROUND: We reviewed the results of a primary total knee arthroplasty (TKA) rapid recovery care pathway applied to patients undergoing aseptic revision TKA. We sought to determine (1) the frequency of postoperative day (POD) 1 discharge, (2) the risk of adverse events, and (3) patient characteristics or surgical factors associated with failure to discharge on POD 1. METHODS: The source population was revision TKAs performed by a single surgeon at an academic medical center from 2016 to 2019 (n = 94). A primary TKA rapid recovery care pathway was applied to all patients who underwent aseptic revision TKA involving both femoral and tibial components (n = 33). Patients discharged on POD 1 (n = 21) were compared with those discharged on POD 2 or later (n = 12). RESULTS: The study cohort was 70% women, 12% under-represented minorities, and 70% government insured. Patients each had an average of 5 comorbidities. The average length of stay was 1.7 days, with 64% of patients discharged on POD 1. Ninety-seven percent of patients were discharged home. Although 18% of patients presented to the emergency room (ER) after discharge, there was no increased risk of readmission (P = .9336) or return to the ER (P = .9849) with POD 1 discharge. The LOS was unaffected by patient characteristics or complexity of surgical reconstruction. CONCLUSIONS: Using a rapid recovery care pathway for aseptic revision TKA is feasible at an academic medical center. All patients may be considered for this pathway. Close postoperative monitoring is essential to minimizing ER visits, which are not uncommon.

Developing "Herd Immunity" in a Civilian Community Through Incorporation of "Just-In-Time" Tourniquet Application Training.

INTRODUCTION: Herd immunity, a concept normally applied in vaccinated populations, is a preventative measure to determine if a significant portion of a population can protect vulnerable individuals against a certain disease. Like vaccines, tourniquet education can be a form of herd immunity to protect vulnerable individuals in a population and prevent the loss of life from a peripheral hemorrhage. The authors have identified a deficiency in simple, quick, and effective hemorrhage control education. Therefore, to maximize herd immunity, the novel educational platform evaluates the efficacy of "Just-in-Time" (JiT) tourniquet application training. HYPOTHESIS/PROBLEM: The authors hypothesize that the utilization of JiT training will be effective in promoting both competence and confidence for individuals to utilize tourniquets in response to a disaster environment. METHODS: This Institutional Review Board-approved study recruited medical students who were trained in hemorrhage control measures at a Level 1 Trauma Center. Tourniquet training sessions were held, and naïve civilians received tourniquet education. The subjects received a five- to ten-minute lesson on indications, contraindications, and application techniques of commercial and improvisational tourniquets. Participants subsequently applied a tourniquet to an instructor's arm to demonstrate proper tourniquet application for a brachial artery hemorrhage. Pre- and post-educational surveys were completed to test participant competency and confidence. RESULTS: Of the 104 subjects who completed the course, 97 had no prior training in hemorrhage control techniques, including commercial and improvisational tourniquet application. The mean pre-test score was 2.27/5.00 and the mean post-test score was 4.38/5.00, P <.001 (n = 97). When queried "How competent would you feel applying a tourniquet (commercial or improvisational) on an individual with a bleeding wound?" 92/97 felt confident (95%), one felt less confident, and four felt no difference in confidence levels (P <.001). CONCLUSION: Just-in-Time training is an effective method in teaching naïve civilians proper tourniquet application. This platform could serve as an alternative to more extensive training programs and requires less time, costs, and resources. If a significant number of individuals in a local community can effectively apply a tourniquet in a disaster scenario, a "herd immunity" effect could be achieved to control peripheral hemorrhages.

Mini-GAGR, an intranasally applied polysaccharide, activates the neuronal Nrf2-mediated antioxidant defense system.

Oxidative stress triggers and exacerbates neurodegeneration in Alzheimer's disease (AD). Various antioxidants reduce oxidative stress, but these agents have little efficacy due to poor blood-brain barrier (BBB) permeability. Additionally, single-modal antioxidants are easily overwhelmed by global oxidative stress. Activating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream antioxidant system are considered very effective for reducing global oxidative stress. Thus far, only a few BBB-permeable agents activate the Nrf2-dependent antioxidant system. Here, we discovered a BBB-bypassing Nrf2-activating polysaccharide that may attenuate AD pathogenesis. Mini-GAGR, a 0.7-kDa cleavage product of low-acyl gellan gum, increased the levels and activities of Nrf2-dependent antioxidant enzymes, decreased reactive oxygen species (ROS) under oxidative stress in mouse cortical neurons, and robustly protected mitochondria from oxidative insults. Moreover, mini-GAGR increased the nuclear localization and transcriptional activity of Nrf2 similarly to known Nrf2 activators. Mechanistically, mini-GAGR increased the dissociation of Nrf2 from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1), and induced phosphorylation and nuclear translocation of Nrf2 in a protein kinase C (PKC)- and fibroblast growth factor receptor (FGFR1)-dependent manner. Finally, 20-day intranasal treatment of 3xTg-AD mice with 100 nmol of mini-GAGR increased nuclear p-Nrf2 and growth-associated protein 43 (GAP43) levels in hippocampal neurons, reduced p-tau and ß-amyloid (Aß) peptide-stained neurons, and improved memory. The BBB-bypassing Nrf2-activating polysaccharide reported here may be effective in reducing oxidative stress and neurodegeneration in AD.

Sbg1 Is a Novel Regulator for the Localization of the ß-Glucan Synthase Bgs1 in Fission Yeast.

Glucan synthases synthesize glucans, complex polysaccharides that are the major components in fungal cell walls and division septa. Studying regulation of glucan synthases is important as they are essential for fungal cell survival and thus popular targets for anti-fungal drugs. Linear 1,3-ß-glucan is the main component of primary septum and is synthesized by the conserved ß-glucan synthase Bgs1 in fission yeast cytokinesis. It is known that Rho1 GTPase regulates Bgs1 catalytic activity and the F-BAR protein Cdc15 plays a role in Bgs1 delivery to the plasma membrane. Here we characterize a novel protein Sbg1 that is present in a complex with Bgs1 and regulates its protein levels and localization. Sbg1 is essential for contractile-ring constriction and septum formation during cytokinesis. Sbg1 and Bgs1 physically interact and are interdependent for localization to the plasma membrane. Bgs1 is less stable and/or mis-targeted to vacuoles in sbg1 mutants. Moreover, Sbg1 plays an earlier and more important role in Bgs1 trafficking and localization than Cdc15. Together, our data reveal a new mode of regulation for the essential ß-glucan synthase Bgs1 by the novel protein Sbg1.