Objective To define the aerosol and droplet risks associated with endonasal drilling and to identify mitigation strategies. Study Design Simulation series with fluorescent 3-dimensional (3D) printed sinonasal models and deidentified cadaveric heads. Settings Dedicated surgical laboratory. Subjects and Methods Cadaveric specimens irrigated with fluorescent tracer and fluorescent 3D-printed models were drilled. A cascade impactor was used to collect aerosols and small droplets of various aerodynamic diameters under 15 µm. Large droplet generation was measured by evaluating the field for fluorescent debris. Aerosol plumes through the nares were generated via nebulizer, and mitigation measures, including suction and SPIWay devices, nasal sheaths, were evaluated regarding reduction of aerosol escape from the nose. Results The drilling of cadaveric specimens without flexible suction generated aerosols ≤3.30 µm, and drilling of 3D sinonasal models consistently produced aerosols ≤14.1 µm. Mitigation with SPIWay or diameter-restricted SPIWay produced same results. There was minimal field contamination in the cadaveric models, 0% to 2.77% field tarp area, regardless of drill burr type or drilling location; cutting burr drilling without suction in the 3D model yielded the worst contamination field (36.1%), followed by coarse diamond drilling without suction (19.4%). The simple placement of a flexible suction instrument in the nasal cavity or nasopharynx led to complete elimination of all aerosols ≤14.1 µm, as evaluated by a cascade impactor positioned immediately at the nares. Conclusion Given the findings regarding aerosol risk reduction, we strongly recommend that physicians use a suction instrument in the nasal cavity or nasopharynx during endonasal surgery in the COVID-19 era.
Objective: During the COVID-19 era, a reliable method for tracing aerosols and droplets generated during otolaryngology procedures is needed to accurately assess contamination risk and to develop mitigation measures. Prior studies have not investigated the reliability of different fluorescent tracers for the purpose of studying aerosols and small droplets. Objectives include (1) comparing vitamin B2, fluorescein, and a commercial fluorescent green dye in terms of particle dispersion pattern, suspension into aerosols and small droplets, and fluorescence in aerosolized form and (2) determining the utility of vitamin B2 as a fluorescent tracer coating the aerodigestive tract mucosa in otolaryngology contamination models. Methods: Vitamin B2, fluorescein, and a commercial fluorescent dye were aerosolized using a nebulizer and passed through the nasal cavity from the trachea in a retrograde-intubated cadaveric head. In another scenario, vitamin B2 was irrigated to coat the nasal cavity and nasopharyngeal mucosa of a cadaveric head for assessment of aerosol and droplet generation from endonasal drilling. A cascade impactor was used to collect aerosols and small droplets ≤14.1 µm based on average aerodynamic diameter, and the collection chambers were visualized under UV light. Results: When vitamin B2 was nebulized, aerosols ≤5.4 µm were generated and the collected particles were fluorescent. When fluorescein and the commercial water tracer dye were nebulized, aerosols ≤8.61 µm and ≤2.08 µm respectively were generated, but the collected aerosols did not appear visibly fluorescent. Endonasal drilling in the nasopharynx coated with vitamin B2 irrigation yielded aerosols ≤3.30 µm that were fluorescent under UV light. Conclusion: Vitamin B2’s reliability as a fluorescent tracer when suspended in aerosols and small droplets ≤14.1 µm and known mucosal safety profile make it an ideal compound compared to fluorescein and commercial water-based fluorescent dyes for use as a safe fluorescent tracer in healthcare contamination models especially with human subjects.
Obesity is a global epidemic and a major predisposing factor for cancer. Increasing evidence shows that obesity-associated stress is a key driver of cancer risk and progression. Previous work has identified the phase-separation organelles, stress granules (SG), as mutant KRAS–dependent mediators of stress adaptation. However, the dependence of tumorigenesis on these organelles is unknown. Here, we establish a causal link between SGs and pancreatic ductal adenocarcinoma (PDAC). Importantly, we uncover that dependence on SGs is drastically heightened in obesity-associated PDAC. Furthermore, we identify a previously unknown regulator and component of SGs, namely, the serine/arginine protein kinase 2 (SRPK2), as a specific determinant of SG formation in obesity-associated PDAC. We show that SRPK2-mediated SG formation in obesity-associated PDAC is driven by hyperactivation of the IGF1/PI3K/mTOR/S6K1 pathway and that S6K1 inhibition selectively attenuates SGs and impairs obesity-associated PDAC development. Significance: We show that stress adaptation via the phase-separation organelles SGs mediates PDAC development. Moreover, preexisting stress conditions such as obesity are a driving force behind tumor SG dependence, and enhanced SG levels are key determinants and a chemopreventive target for obesity-associated PDAC.
While Toll-like receptors (TLRs) represent one of the best characterized innate immune pathways, evidence suggests that TLRs are not restricted to innate leukocytes and some epithelial cells, but are also expressed in T cells. Specifically, published evidence focusing on FoxP3+ regulatory T cells demonstrate that they express functional TLR2, which is already known among the TLR family for its association with immune suppression; however, little is known about the relationship between T cell-intrinsic TLR2 binding and cytokine production, T cell differentiation, or T cell receptor (TCR) stimulation. Here, we demonstrate that TCR and TLR2 co-stimulation provides a T cell-intrinsic signal which generates a dramatic, synergistic cytokine response dominated by IL-10. Importantly, the response was not seen in either CD4+CD25+ or CD4+FoxP3+ Tregs, yet resulted in the expansion of a suppressive CD4+CD25+CD62L-CD44+CD45Rbhi effector/memory T cell subset not typically associated with immune inhibition. This study reveals the striking ability of a prototypical innate immune receptor to trigger a potent and suppressive IL-10 response in effector/memory T cells, supporting the notion that TLR2 is a co-regulatory receptor on T cells.
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