A nationwide survey of intraoperative management for one-lung ventilation in Taiwan: time to accountable for diversity in protective lung ventilation.

BACKGROUND: There is a major paradigm shift for intraoperative mechanical ventilator support by the introduction of lung protective ventilation strategies to reduce postoperative pulmonary complications and improve overall clinical outcomes in non-thoracic surgeries. However, there is currently a lack of standardized practice guideline for lung protection during thoracic surgeries that require one-lung ventilation (OLV). This study aimed to collect the expert opinions of the thoracic anesthesiologists in perioperative care for OLV surgery in Taiwan. METHODS: This prospective cross-sectional study was undertaken in 16 tertiary hospitals in Taiwan from January to February 2019. A structured survey form was distributed across the participating hospitals and the thoracic anesthesiologists were invited to complete the form voluntarily. The survey form consisted of three parts, including the basic information of the institutional anesthesia care standards, ventilatory settings for a proposed patient receiving OLV surgery and expert opinions on OLV. RESULTS: A total of 71 thoracic anesthesiologists responded to the survey. Double-lumen tubes are the most commonly used (93.8%) airway devices for OLV. The most commonly recommended ventilator setting during OLV is a tidal volume of 6-7 ml/kg PBW (67.6%) and a PEEP level of 4-6 cmH2O (73.5%). Dual controlled ventilator modes are used by 44.1% of the anesthesiologists. During OLV, high oxygen fraction (FiO2 > 0.8) is more commonly supplemented to achieve an oxygen saturation higher than 94%. The consensus of anesthesiologists on the indices for lung protection in thoracic surgery is considerably low. Large majority of the anesthesiologists (91.5%) highly recommend that an international clinical practice guideline on the protective lung ventilation strategy for thoracic anesthesia should be established. CONCLUSIONS: This study found that the thoracic anesthesiologists in Taiwan share certain common practices in ventilator support during OLV. However, they are concerned about the lack of fundamental clinical evidences to support the beneficial outcomes of the current lung protective strategies applicable to OLV. Large-scale trials are needed to form an evidence-based clinical practice guideline for thoracic anesthesia.

The (+)-Brevipolide H Displays Anticancer Activity against Human Castration-Resistant Prostate Cancer: The Role of Oxidative Stress and Akt/mTOR/p70S6K-Dependent Pathways in G1 Checkpoint Arrest and Apoptosis.

Because conventional chemotherapy is not sufficiently effective against prostate cancer, various examinations have been performed to identify anticancer activity of naturally occurring components and their mechanisms of action. The (+)-brevipolide H, an α-pyrone-based natural compound, induced potent and long-term anticancer effects in human castration-resistant prostate cancer (CRPC) PC-3 cells. Flow cytofluorometric analysis with propidium iodide staining showed (+)-brevipolide H-induced G1 arrest of cell cycle and subsequent apoptosis through induction of caspase cascades. Since Akt/mTOR pathway has been well substantiated in participating in cell cycle progression in G1 phase, its signaling and downstream regulators were examined. Consequently, (+)-brevipolide H inhibited the signaling pathway of Akt/mTOR/p70S6K. The c-Myc inhibition and downregulation of G1 phase cyclins were also attributed to (+)-brevipolide H action. Overexpression of myristoylated Akt significantly rescued mTOR/p70S6K and downstream signaling under (+)-brevipolide H treatment. ROS and Ca2+, two key mediators in regulating intracellular signaling, were determined, showing that (+)-brevipolide H interactively induced ROS production and an increase of intracellular Ca2+ levels. The (+)-Brevipolide H also induced the downregulation of anti-apoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL) and loss of mitochondrial membrane potential, indicating the contribution of mitochondrial dysfunction to apoptosis. In conclusion, the data suggest that (+)-brevipolide H displays anticancer activity through crosstalk between ROS production and intracellular Ca2+ mobilization. In addition, suppression of Akt/mTOR/p70S6K pathway associated with downregulation of G1 phase cyclins contributes to (+)-brevipolide H-mediated anticancer activity, which ultimately causes mitochondrial dysfunction and cell apoptosis. The data also support the biological significance and, possibly, clinically important development of natural product-based anticancer approaches.