RESUMEN
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.
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Otitis Media con Derrame , Otitis Media , Otolaringología , Niño , Humanos , Lactante , Otitis Media con Derrame/cirugía , Ventilación del Oído Medio , Otitis Media/cirugía , OtorrinolaringólogosRESUMEN
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.
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Carcinoma Ductal Pancreático , Obesidad , Neoplasias Pancreáticas , Proteínas Serina-Treonina Quinasas , Gránulos de Estrés , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Humanos , Obesidad/complicaciones , Obesidad/genética , Obesidad/metabolismo , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Gránulos de Estrés/genética , Gránulos de Estrés/metabolismo , Neoplasias PancreáticasRESUMEN
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.
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Seguro , Otitis Media , Niño , Enfermedad Crónica , Estudios de Seguimiento , Humanos , Lactante , Ventilación del Oído Medio/métodos , Otitis Media/cirugía , Estudios RetrospectivosRESUMEN
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 14.1âµm. 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.
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COVID-19/prevención & control , Mastoidectomía/efectos adversos , Aerosoles , COVID-19/transmisión , Cadáver , Humanos , Mastoidectomía/instrumentación , Mastoidectomía/métodos , SARS-CoV-2RESUMEN
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.
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Aerosoles/efectos adversos , COVID-19 , Transmisión de Enfermedad Infecciosa/prevención & control , Endoscopía , Otolaringología , Ajuste de Riesgo/métodos , Succión , COVID-19/prevención & control , COVID-19/transmisión , Cadáver , Endoscopía/efectos adversos , Endoscopía/instrumentación , Endoscopía/métodos , Humanos , Otolaringología/métodos , Otolaringología/normas , Evaluación de Resultado en la Atención de Salud , Equipo de Protección Personal/clasificación , Equipo de Protección Personal/virología , Proyectos de Investigación , Medición de Riesgo/métodos , SARS-CoV-2 , Succión/efectos adversos , Succión/instrumentación , Succión/métodosRESUMEN
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.
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COVID-19/transmisión , Transmisión de Enfermedad Infecciosa , Colorantes Fluorescentes , Modelos Biológicos , Nasofaringe/cirugía , Riboflavina , Aerosoles , Cadáver , Endoscopía , Fluoresceína , Humanos , Modelos Anatómicos , Nebulizadores y Vaporizadores , Otolaringología , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Tamaño de la Partícula , SARS-CoV-2RESUMEN
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.
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Transfusión de Componentes Sanguíneos , Servicios Médicos de Urgencia , Plasma , Heridas y Lesiones/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia , Heridas y Lesiones/mortalidadRESUMEN
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.
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Antivirales/uso terapéutico , Carbohidratos/sangre , Enfermedades Cardiovasculares/complicaciones , Glicómica , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Adulto , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Femenino , Glicosilación , Infecciones por VIH/sangre , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prueba de Estudio ConceptualRESUMEN
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.