Adherence to Tympanostomy Tube Clinical Practice Guidelines in an Advanced Practice Provider Clinic.

OBJECTIVE: We compared adherence rates by attending otolaryngologists (OTOs) and advanced practice providers (APPs) to the 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline (CPG) for children with recurrent acute otitis media (RAOM) undergoing bilateral myringotomy and tympanostomy tube placement (BMT). METHODS: Patients aged 6 months to 12 years old undergoing BMT for RAOM who had a pre-operative visit with an independent APP or OTO were reviewed. Patients satisfied CPG criteria if middle ear effusion was identified at the pre-operative visit (pre-op) or if they did not have effusion but met exception criteria based on their risk for developmental difficulties and contraindications to medical therapy. Adherence rates between APPs and OTOs were compared. Agreement between pre-op and time-of-surgery middle ear effusion identification was assessed. RESULTS: Nine hundred twenty-three patients were included. Six hundred one patients were seen by OTOs and 322 by APPs. Middle ear effusion was identified at pre-op in 84% of APP patients and in 76% of OTO patients (P = .005). Eight percent of APP patients and 11% of OTO patients met exception criteria (P = .138). Overall, 87% of OTO patients and 92% of APP patients met either CPG or exception criteria for BMT (P = .037). A logistic regression model demonstrated that pre-op provider type did not significantly impact rates of agreement between pre-op visit and time-of-surgery middle ear effusion identification. CONCLUSIONS: Independent APP-led clinics can reliably and effectively deliver evidence-based care for prevalent conditions such as RAOM at similar rates of adherence to CPGs as OTOs.

Stress Granules Determine the Development of Obesity-Associated Pancreatic Cancer.

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. This article is highlighted in the In This Issue feature, p. 1825.

Effect of Insurance Type on Postoperative Tympanostomy Tube Follow-up.

OBJECTIVE: Bilateral myringotomy with tube insertion (BMT) is a common procedure performed in children. Appropriate follow-up is necessary to ensure management of postoperative sequalae. The objectives are to investigate (1) the relationship between insurance type and postoperative follow-up attendance and (2) the effect of follow-up on need for further care after BMT. STUDY DESIGN: Retrospective cohort study. SETTING: The study included patients <3 years of age undergoing BMT for recurrent acute otitis media at a tertiary care children's hospital within a single year and followed for 3 years. Patients were excluded if they had received a prior BMT; underwent a concurrent otolaryngologic procedure; or had a syndromic diagnosis, craniofacial abnormality, or any significant cardiac or respiratory comorbidity. METHODS: Number of follow-up appointments, demographics, socioeconomic status, and postoperative outcomes were analyzed. RESULTS: A total of 734 patients were included with mean (SD) age of 1.4 years (0.50). The majority of patients had private insurance (520/734, 70.8%). Patients with public insurance attended fewer postoperative appointments (1.5 vs 1.8, P < .001) and had a higher incidence of BMT-related emergency department (ED) visits (10.3% vs 3.8%, P = .001). There was no significance found when different insurance providers were compared. An adjusted multivariate regression analysis showed that patients with private insurance were more likely to attend postoperative appointments (odds ratio, 3.52 [95% CI, 2.12-5.82]; P < .001) and less likely to have a BMT-related ED visit (odds ratio, 0.42 [95% CI, 0.20-0.89]; P = .024). CONCLUSION: Insurance type is related to outcomes after the treatment of recurrent acute otitis media with BMT. Future studies that survey individuals will help identify barriers that contribute to patient absence at follow-ups and need for subsequent ED visits.

Aerosol and Droplet Risk of Common Otolaryngology Clinic Procedures.

OBJECTIVES: Define aerosol and droplet risks associated with routine otolaryngology clinic procedures during the COVID-19 era. METHODS: Clinical procedures were simulated in cadaveric heads whose oral and nasal cavities were coated with fluorescent tracer (vitamin B2) and breathing was manually simulated through retrograde intubation. A cascade impactor placed adjacent to the nares collected generated particles with aerodynamic diameters ≤14.1 µm. The 3D printed models and syringes were used to simulate middle and external ear suctioning as well as open suctioning, respectively. Provider's personal protective equipment (PPE) and procedural field contamination were also recorded for all trials using vitamin B2 fluorescent tracer. RESULTS: The positive controls of nebulized vitamin B2 produced aerosol particles ≤3.30 µm and endonasal drilling of a 3D model generated particles ≤14.1 µm. As compared with positive controls, aerosols and small droplets with aerodynamic diameter ≤14.1 µm were not detected during rigid nasal endoscopy, flexible fiberoptic laryngoscopy, and rigid nasal suction of cadavers with simulated breathing. There was minimal to no field contamination in all 3 scenarios. Middle and external ear suctioning and open container suctioning did not result in any detectable droplet contamination. The clinic suction unit contained all fluorescent material without surrounding environmental contamination. CONCLUSION: While patients' coughing and sneezing may create a baseline risk for providers, this study demonstrates that nasal endoscopy, flexible laryngoscopy, and suctioning inherently do not pose an additional risk in terms of aerosol and small droplet generation. An overarching generalization cannot be made about endoscopy or suctioning being an aerosol generating procedure. LEVEL OF EVIDENCE: 3.

Droplet and Aerosol Generation With Mastoidectomy During the COVID-19 Pandemic: Assessment of Baseline Risk and Mitigation Measures With a High-performance Cascade Impactor.

HYPOTHESIS: Aerosols are generated during mastoidectomy and mitigation strategies may effectively reduce aerosol spread. BACKGROUND: An objective understanding of aerosol generation and the effectiveness of mitigation strategies can inform interventions to reduce aerosol risk from mastoidectomy and other open surgeries involving drilling. METHODS: Cadaveric and fluorescent three-dimensional printed temporal bone models were drilled under variable conditions and mitigation methods. Aerosol production was measured with a cascade impactor set to detect particle sizes under 14.1 µm. Field contamination was determined with examination under UV light. RESULTS: Drilling of cadaveric bones and three-dimensional models resulted in strongly positive aerosol production, measuring positive in all eight impactor stages for the cadaver trials. This occurred regardless of using coarse or cutting burs, irrigation, a handheld suction, or an additional parked suction. The only mitigation factor that led to a completely negative aerosol result in all eight stages was placing an additional microscope drape to surround the field. Bone dust was scattered in all directions from the drill, including on the microscope, the surgeon, and visually suspended in the air for all but the drape trial. CONCLUSIONS: Aerosols are generated with drilling the mastoid. Using an additional microscope drape to cover the surgical field was an effective mitigation strategy to prevent fine aerosol dispersion while drilling.

Advanced Practice Provider Clinics: Expediting Care For Children Undergoing Tympanostomy Tube Placement.

OBJECTIVE/HYPOTHESIS: Advanced practice provider (APP) employment is becoming common in pediatric otolaryngology practices, though few studies have evaluated the consequences that APP-led clinics have on access to care. The objectives of this study were: 1) to investigate whether access to bilateral myringotomy with tympanostomy tube placement (BMT) for recurrent acute otitis media (RAOM) differed between patients seen in otolaryngologist and APP-led clinics 2) to compare clinical characteristics of patients seen by provider type. METHODS: Retrospective cohort study at an academic, tertiary care pediatric otolaryngology practice. All children were <18 years old and underwent evaluation for RAOM followed by BMT. We compared time in days from scheduling pre-operative appointment to appointment date and time from appointment to BMT between patients seen by APPs and otolaryngologists using Mann-Whitney U tests and multivariate linear regression models. We compared clinical characteristics by provider type using Mann-Whitney U tests and Fisher exact tests. RESULTS: A total of 957 children were included. Children seen by APPs had significantly shorter wait times for appointments (median 19 vs. 39 days, P < .001) and shorter times from preoperative appointment to BMT (median 25 vs. 37 days, P < .001). Patients seen by otolaryngologists had increased prevalence of craniofacial abnormalities, Down Syndrome, hearing loss, history of otologic surgery, and higher ASA physical status classification. CONCLUSIONS: Children seen by APPs received care more quickly than those seen by otolaryngologists. Patients seen by otolaryngologists tended to be more medically complex. Implementation of independent APP clinics may expedite and improve access to BMT for children with RAOM. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2133-2140, 2021.

Novel Use of Vitamin B2 as a Fluorescent Tracer in Aerosol and Droplet Contamination Models in Otolaryngology.

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.

Droplet and Aerosol Generation With Endonasal Surgery: Methods to Mitigate Risk During the COVID-19 Pandemic.

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.

Massive transfusion and the response to prehospital plasma: It is all in how you define it.

BACKGROUND: A recent analysis derived from the Prehospital Air Medical Plasma trial data set demonstrated no significant independent plasma survival benefit in those who required massive transfusion (≥10 units of red cells in 24 hours). The definition of massive transfusion has evolved over time to minimize bias and predict those at highest risk of death. We sought to characterize the definition of massive transfusion, their associated mortality risks and the survival benefit associated with prehospital plasma. METHODS: A secondary analysis was performed using data from a recent prehospital plasma trial. Patients transferred directly from the scene were characterized. We defined historic massive transfusion using ≥10 units red cells in 24 hours and critical administration threshold (CAT) as ≥3 units per hour in the first hour (CAT1hr) or in any of the first 4 hours (CAT4hr) from arrival. The primary outcome was 30-day mortality. Kaplan-Meier analysis and Cox hazard regression were used to characterize the survival benefit of prehospital plasma. RESULTS: There were a total of 390 enrolled patients who were transferred from the scene and represent the study cohort. Overall, 126 patients were positive for the CAT1hr metric, 183 patients were positive for the CAT4hr metric and 84 patients were positive for historic massive transfusion metric. The overall study mortality rate for those patients who met each transfusion definition was 13.1%, 17.4% and 10.0%, respectively. The CAT4hr metric had the lowest potential for survival bias. Kaplan-Meier survival analysis demonstrated a prehospital plasma survival benefit in the patients who were CAT4hr positive. CONCLUSION: The current analysis demonstrates the superior utility of the CAT4hr definition with optimization of survival bias while conserving mortality risk prediction. This transfusion definition was associated with a prehospital plasma survival benefit and may be the most appropriate definition of massive transfusion for pragmatic studies which focus on hemorrhagic shock. LEVEL OF EVIDENCE: Epidemiologic, Level II.

Evaluating Stress Granules in Pancreatic Cancer In Vitro and In Vivo.

Stress granules are nonmembranous organelles that function as a stress-adaptation mechanism. We have recently shown that stress granules are mobilized by mutant KRAS pancreatic cancer cells under stress to enhance tumor fitness and survival. In this chapter, we outline a method for inducing, detecting, and quantifying stress granules in pancreatic cancer cells in vitro and in vivo. This method can be utilized to better understand the mechanisms driving stress granule formation and their role in pancreatic tumorigenesis.

Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.

Despite effective control of HIV infection with antiretroviral drugs, individuals with HIV have high incidences of secondary diseases. These sequelae, such as cardiovascular disease (CVD), are poorly understood and represent a major health burden. To date, predictive biomarkers of HIV-associated secondary disease have been elusive, making preventative clinical management essentially impossible. Here, we applied a newly developed and easy to deploy, multitarget, and high-throughput glycomic analysis to banked HIV+ human plasma samples to determine whether the glycome may include biomarkers that predict future HIV-associated cardiovascular events or CVD diagnoses. Using 324 patient samples, we identified a glycomic fingerprint that was predictive of future CVD events but independent of CD4 counts, diabetes, age, and birth sex, suggesting that the plasma glycome may serve as a biomarker for specific HIV-associated sequelae. Our findings constitute the discovery of novel glycan biomarkers that could classify patients with HIV with elevated risk for CVD and reveal the untapped prognostic potential of the plasma glycome in human disease.-Oswald, D. M., Sim, E. S., Baker, C., Farhan, O., Debanne, S. M., Morris, N. J., Rodriguez, B. G., Jones, M. B., Cobb, B. A. Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.

T cell-intrinsic TLR2 stimulation promotes IL-10 expression and suppressive activity by CD45RbHi T cells.

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.