Assessing Provider Adherence To A Lung Protective Ventilation Protocol In Patients Undergoing Thoracic Surgery Using One-Lung Ventilation.

Patients undergoing one-lung ventilation (OLV) are at risk for lung injury leading to postoperative pulmonary complications (PPCs). Lung protective ventilation (LPV) challenges traditional anesthetic management by using lower tidal volumes, individualized positive end-expiratory pressure (PEEP), and recruitment maneuvers (RMs). LPV reduces driving pressure when properly applied, which reduces the incidence of PPCs. An LPV protocol was developed and implemented for this study for patients undergoing one-lung ventilation. Knowledge and confidence were measured prior to, immediately following, and 12 weeks after an educational offering and distribution of cognitive aids. Clinical data were collected 12 weeks prior to implementation, immediately after implementation, and again at 12 weeks post-implementation. There was a significant increase in provider knowledge regarding LPV (P = .015). A significant adherence to monitoring driving pressures (P < .05) was observed at 12 weeks post-implementation. There were increases in adherence to each component (tidal volume, PEEP, RM, and FiO2) as well as overall adherence (P = .356). Implementation of the protocol resulted in increased adherence to lung protective strategies, including a statistically significant decrease (P < 0.05) in driving pressure which has been shown to reduce complications in patients having thoracic surgery with OLV.

JS-K, a nitric oxide-releasing prodrug, modulates ß-catenin/TCF signaling in leukemic Jurkat cells: evidence of an S-nitrosylated mechanism.

ß-Catenin is a central player of the Wnt signaling pathway that regulates cell-cell adhesion and may promote leukemia cell proliferation. We examined whether JS-K, an NO-donating prodrug, modulates the Wnt/ß-catenin/TCF-4 signaling pathway in Jurkat T-Acute Lymphoblastic Leukemia cells. JS-K inhibited Jurkat T cell growth in a concentration and time-dependent manner. The IC(50)s for cell growth inhibition were 14±0.7 and 9±1.2µM at 24 and 48h, respectively. Treatment of the cells with JS-K for 24h, caused a dose-dependent increase in apoptosis from 16±3.3% at 10µM to 74.8±2% at 100µM and a decrease in proliferation. This growth inhibition was also due, in part, to alterations in the different phases of the cell cycle. JS-K exhibited a dose-dependent cytotoxicity as measured by LDH release at 24h. However, between 2 and 8h, LDH release was less than 20% for any indicated JS-K concentration. The ß-catenin/TCF-4 transcriptional inhibitory activity was reduced by 32±8, 63±5, and 93±2% at 2, 10, and 25µM JS-K, respectively, based on luciferase reporter assays. JS-K reduced nuclear ß-catenin and cyclin D1 protein levels, but cytosolic ß-catenin expression did not change. Based on a time-course assay of S-nitrosylation of proteins by a biotin switch assay, S-nitrsolyation of nuclear ß-catenin was determined to precede its degradation. A comparison of the S-nitrosylated nuclear ß-catenin to the total nuclear ß-catenin showed that ß-catenin protein levels were degraded at 24h, while S-nitrosylation of ß-catenin occurred earlier at 0-6h. The NO scavenger PTIO abrogated the JS-K mediated degradation of ß-catenin demonstrating the need for NO.