Quantification of Aerosol Particle Concentrations During Endoscopic Sinonasal Surgery in the Operating Room.

BACKGROUND: Recent indirect evidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission during endoscopic endonasal procedures has highlighted the dearth of knowledge surrounding aerosol generation with these procedures. As we adapt to function in the era of Coronavirus Disease 2019 (COVID-19) a better understanding of how surgical techniques generate potentially infectious aerosolized particles will enhance the safety of operating room (OR) staff and learners. OBJECTIVE: To provide greater understanding of possible SARS-CoV-2 exposure risk during endonasal surgeries by quantifying increases in airborne particle concentrations during endoscopic sinonasal surgery. METHODS: Aerosol concentrations were measured during live-patient endoscopic endonasal surgeries in ORs with an optical particle sizer. Measurements were taken throughout the procedure at six time points: 1) before patient entered the OR, 2) before pre-incision timeout during OR setup, 3) during cold instrumentation with suction, 4) during microdebrider use, 5) during drill use and, 6) at the end of the case prior to extubation. Measurements were taken at three different OR position: surgeon, circulating nurse, and anesthesia provider. RESULTS: Significant increases in airborne particle concentration were measured at the surgeon position with both the microdebrider (p = 0.001) and drill (p = 0.001), but not for cold instrumentation with suction (p = 0.340). Particle concentration did not significantly increase at the anesthesia position or the circulator position with any form of instrumentation. Overall, the surgeon position had a mean increase in particle concentration of 2445 particles/ft3 (95% CI 881 to 3955; p = 0.001) during drill use and 1825 particles/ft3 (95% CI 641 to 3009; p = 0.001) during microdebrider use. CONCLUSION: Drilling and microdebrider use during endonasal surgery in a standard operating room is associated with a significant increase in airborne particle concentrations. Fortunately, this increase in aerosol concentration is localized to the area of the operating surgeon, with no detectable increase in aerosol particles at other OR positions.

Potent benzoazepinone γ-secretase modulators with improved bioavailability.

The triazolyl amide γ-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain Aß42 lowering maintained in both transgenic mouse and rat.