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The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
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Betacoronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Neumonía Viral/patología , Neumonía Viral/virología , Sistema Respiratorio/virología , Genética Inversa/métodos , Anciano , Enzima Convertidora de Angiotensina 2 , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , COVID-19 , Línea Celular , Células Cultivadas , Chlorocebus aethiops , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Fibrosis Quística/patología , ADN Recombinante , Femenino , Furina/metabolismo , Humanos , Inmunización Pasiva , Pulmón/metabolismo , Pulmón/patología , Pulmón/virología , Masculino , Persona de Mediana Edad , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Mucosa Nasal/virología , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/inmunología , Sistema Respiratorio/patología , SARS-CoV-2 , Serina Endopeptidasas/metabolismo , Células Vero , Virulencia , Replicación Viral , Sueroterapia para COVID-19RESUMEN
INTRODUCTION: The persistent lack of racial and ethnic diversity within the field of otolaryngology calls for an analysis of potential bias within the residency application system. Letters of recommendation (LORs) and personal statements (PSs) are the most important subjective application constituents. This subjectivity predisposes these components to implicit bias. In applications to various surgical subspecialties, prior linguistic studies assessing bias in reviews of LOR show race-based differences. Thus far, racial and ethnic linguistic differences in LORs for otolaryngology applicants have not been analyzed in the literature. METHODS: LORs and PSs were abstracted from otolaryngology - head and neck surgery applications in the Electronic Residency Application Service for the 2019-20 and 2020-21 application cycles. Linguistic Inquiry and Word Count 2015 was used for quantitative analysis of emotional, cognitive, and structural components of written text. RESULTS: Race-pair analysis of the 2019-2021 application cycles revealed higher mean "teaching" scores for LORs for Asian, black, Hispanic, and white applicants when compared to applicants who self-identified as Other. White applicants had lower scores for the terms "research" and "analytic" when compared to Asian and black applicants, respectively. Analysis of PSs revealed greater scores for an "authentic" writing style for white versus Asian applicants. White applicants were found to have higher scores for "tone" compared to black applicants. CONCLUSION: Minor racial and ethnic language differences exist in both LORs and PSs. A statistically significant difference was observed among LORs, with the "teaching" term used more frequently for Asian, black, Hispanic, and white applicants compared to self-identified Other individuals. For PSs, statistically significant differences were observed among white applicants, who wrote about themselves using more "authentic" language when compared with Asian applicants and who also had higher scores for "tone" compared to black applicants. Although these differences were statistically significant, the practical impact of the variances is likely small.
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Internado y Residencia , Otolaringología , Humanos , Escritura , Otolaringología/educaciónRESUMEN
Solitary plasmacytoma is a rare neoplasm characterized by localized proliferation of monoclonal plasma cells and is classified as solitary bone or solitary extramedullary plasmacytoma. Here, we present two rare cases of plasmacytoma of the head and neck. The first is a 78-year-old male who presented with a 3-month history of epistaxis and progressive obstruction of the right nasal passage. Computerized tomography (CT) imaging revealed a mass in the right nasal cavity with destruction to the maxillary sinus. An excisional biopsy was performed revealing anaplastic plasmacytoma. The second is a 64-year-old male with a past medical history significant for prostate cancer who presented with a 2-month history of left ear pain and progressive non-tender temporal swelling. A PET/CT revealed a highly avid, destructive, and lytic left temporal mass with no other evidence of distant disease. A left temporal craniectomy and infratemporal fossa dissection revealed plasma cell dyscrasia with monoclonal lambda in situ hybridization. Although plasmacytomas are uncommon tumors of the head and neck, they may mimic other entities that require different treatment. Prompt and accurate diagnosis is critical for appropriate therapeutic decisions and prognosis.
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Plasmacitoma , Masculino , Humanos , Anciano , Persona de Mediana Edad , Plasmacitoma/diagnóstico , Plasmacitoma/cirugía , Plasmacitoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Cavidad Nasal , Cabeza , Cuello/patologíaRESUMEN
INTRODUCTION: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. METHODS: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. RESULTS: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). DISCUSSION/CONCLUSION: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.
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Anafilaxia , Productos Biológicos , Estados Unidos , Humanos , Sistemas de Registro de Reacción Adversa a Medicamentos , Anafilaxia/inducido químicamente , Omalizumab/efectos adversos , United States Food and Drug Administration , Productos Biológicos/efectos adversosRESUMEN
INTRODUCTION: The coronavirus 2019 pandemic has altered how modern healthcare is delivered to patients. Concerns have been raised that masks may hinder effective communication, particularly in patients with hearing loss. The purpose of this study is to determine the effect of masks on speech recognition in adult patients with and without self-reported hearing loss in a clinical setting. METHODS: Adult patients presenting to an otolaryngology clinic were recruited. A digital recording of 36 spondaic words was presented to each participant in a standard clinical exam room. Each word was recorded in 1 of 3 conditions: no mask, surgical mask, or N95 mask. Participants were instructed to repeat back the word. The word recognition score was determined by the percent correctly repeated. RESULTS: A total of 45 participants were included in this study. Overall, the mean word recognition score was 87% without a mask, 78% with a surgical mask, and 61% with an N95 mask. Among the 23 subjects (51.1%) with self-reported hearing loss, the average word recognition score was 46% with an N95 mask compared to 79% in patients who reported normal hearing (p < 0.001). CONCLUSION: Our results suggest that masks significantly decrease word recognition, and this effect is exacerbated with N95 masks, particularly in patients with hearing loss. As masks are essential to allow for safe patient-physician interactions, it is imperative that clinicians are aware they may create a barrier to effective communication.
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Infecciones por Coronavirus , Sordera , Pérdida Auditiva , Percepción del Habla , Adulto , Humanos , Máscaras/efectos adversos , PandemiasRESUMEN
The T1R and T2R families of G protein-coupled receptors (GPCRs) initiate tastant perception by signaling via guanine nucleotide exchange and hydrolysis performed by associated heterotrimeric G proteins (Gαßγ). Heterotrimeric G protein signal termination is sped up by Gα-directed GTPase-accelerating proteins (GAPs) known as the Regulators of G protein Signaling (RGS proteins). Of this family, RGS21 is highly expressed in lingual epithelial cells and we have shown it acting in vitro to decrease the potency of bitterants on cultured cells. However, constitutive RGS21 loss in mice reduces organismal response to GPCR-mediated tastants-opposite to expectations arising from observed in vitro activity of RGS21 as a GAP and inhibitor of T2R signaling. Here, we show reduced quinine aversion and reduced sucrose preference by mice lacking RGS21 does not result from post-ingestive effects, as taste-salient brief-access tests confirm the reduced bitterant aversion and reduced sweetener preference seen using two-bottle choice testing. Eliminating Rgs21 expression after chemosensory system development, via tamoxifen-induced Cre recombination in eight week-old mice, led to a reduction in quinine aversive behavior that advanced over time, suggesting that RGS21 functions as a negative regulator to sustain stable bitter tastant reception. Consistent with this notion, we observed downregulation of multiple T2R proteins in the lingual tissue of Rgs21-deficient mice. Reduced tastant-mediated responses exhibited by mice lacking Rgs21 expression either since birth or in adulthood has highlighted the potential requirement for a GPCR GAP to maintain the full character of tastant signaling, likely at the level of mitigating receptor downregulation.
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Proteínas RGS , Animales , Proteínas de Unión al GTP , Ratones , Proteínas RGS/genética , Proteínas RGS/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , GustoRESUMEN
Heterotrimeric G-protein signaling pathways are vital components of physiology, and many are amenable to pharmacologic manipulation. Here, we identify functional heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent of amoebic colitis. The E. histolytica Gα subunit EhGα1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGßγ dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGα1 highlights unique features and classification outside of conventional mammalian Gα subfamilies. E. histolytica trophozoites overexpressing wildtype EhGα1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGα1-overexpressing trophozoites also display enhanced transmigration across a Matrigel barrier, an effect that may result from altered baseline migration. Inducible expression of a dominant negative EhGα1 variant engenders the converse phenotypes. Transcriptomic studies reveal that modulation of pathogenesis-related trophozoite behaviors by perturbed heterotrimeric G-protein expression includes transcriptional regulation of virulence factors and altered trafficking of cysteine proteases. Collectively, our studies suggest that E. histolytica possesses a divergent heterotrimeric G-protein signaling axis that modulates key aspects of cellular processes related to the pathogenesis of this infectious organism.
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Entamoeba histolytica/inmunología , Entamebiasis/inmunología , Subunidades alfa de la Proteína de Unión al GTP/inmunología , Proteínas Protozoarias/inmunología , Factores de Virulencia/inmunología , Animales , Células CHO , Cricetinae , Cricetulus , Cristalografía por Rayos X , Entamoeba histolytica/enzimología , Entamoeba histolytica/genética , Entamebiasis/enzimología , Entamebiasis/genética , Subunidades alfa de la Proteína de Unión al GTP/química , Subunidades alfa de la Proteína de Unión al GTP/genética , Regulación de la Expresión Génica/inmunología , Factores de Intercambio de Guanina Nucleótido/química , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/inmunología , Humanos , Células Jurkat , Estructura Terciaria de Proteína , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Factores de Intercambio de Guanina Nucleótido Rho , Transcripción Genética/inmunología , Factores de Virulencia/biosíntesis , Factores de Virulencia/químicaRESUMEN
Heterotrimeric G-proteins are molecular switches integral to a panoply of different physiological responses that many organisms make to environmental cues. The switch from inactive to active Gαßγ heterotrimer relies on nucleotide cycling by the Gα subunit: exchange of GTP for GDP activates Gα, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP and inorganic phosphate, thereby reverting Gα to its inactive state. In several genetic studies of filamentous fungi, such as the rice blast fungus Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of Gα subunits is assumed to be GTPase-deficient and thus constitutively active. Here, we demonstrate that Gα(G42R) mutants are not GTPase deficient, but rather incapable of achieving the activated conformation. Two crystal structure models suggest that Arg-42 prevents a typical switch region conformational change upon Gα(i1)(G42R) binding to GDP·AlF(4)(-) or GTP, but rotameric flexibility at this locus allows for unperturbed GTP hydrolysis. Gα(G42R) mutants do not engage the active state-selective peptide KB-1753 nor RGS domains with high affinity, but instead favor interaction with Gßγ and GoLoco motifs in any nucleotide state. The corresponding Gα(q)(G48R) mutant is not constitutively active in cells and responds poorly to aluminum tetrafluoride activation. Comparative analyses of M. oryzae strains harboring either G42R or GTPase-deficient Q/L mutations in the Gα subunits MagA or MagB illustrate functional differences in environmental cue processing and intracellular signaling outcomes between these two Gα mutants, thus demonstrating the in vivo functional divergence of G42R and activating G-protein mutants.
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Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/fisiología , Magnaporthe/patogenicidad , Micosis/genética , Mutación Puntual , Pliegue de Proteína , Sustitución de Aminoácidos/fisiología , Dominio Catalítico/genética , Cristalografía por Rayos X , Subunidades alfa de la Proteína de Unión al GTP/química , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Hordeum/microbiología , Magnaporthe/genética , Magnaporthe/metabolismo , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas Mutantes/fisiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Hojas de la Planta/microbiología , Mutación Puntual/fisiología , Estructura Terciaria de Proteína/genética , Transducción de Señal/genéticaRESUMEN
Because G-protein coupled receptors (GPCRs) continue to represent excellent targets for the discovery and development of small-molecule therapeutics, it is posited that additional protein components of the signal transduction pathways emanating from activated GPCRs themselves are attractive as drug discovery targets. This review considers the drug discovery potential of two such components: members of the "regulators of G-protein signaling" (RGS protein) superfamily, as well as their substrates, the heterotrimeric G-protein α subunits. Highlighted are recent advances, stemming from mouse knockout studies and the use of "RGS-insensitivity" and fast-hydrolysis mutations to Gα, in our understanding of how RGS proteins selectively act in (patho)physiologic conditions controlled by GPCR signaling and how they act on the nucleotide cycling of heterotrimeric G-proteins in shaping the kinetics and sensitivity of GPCR signaling. Progress is documented regarding recent activities along the path to devising screening assays and chemical probes for the RGS protein target, not only in pursuits of inhibitors of RGS domain-mediated acceleration of Gα GTP hydrolysis but also to embrace the potential of finding allosteric activators of this RGS protein action. The review concludes in considering the Gα subunit itself as a drug target, as brought to focus by recent reports of activating mutations to GNAQ and GNA11 in ocular (uveal) melanoma. We consider the likelihood of several strategies for antagonizing the function of these oncogene alleles and their gene products, including the use of RGS proteins with Gα(q) selectivity.
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Descubrimiento de Drogas/métodos , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Proteínas RGS/química , Proteínas RGS/metabolismo , Transducción de Señal , Animales , Subunidades alfa de la Proteína de Unión al GTP/química , Subunidades alfa de la Proteína de Unión al GTP/genética , Guanosina Trifosfato/metabolismo , Proteínas de Unión al GTP Heterotriméricas/química , Proteínas de Unión al GTP Heterotriméricas/genética , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Humanos , Terapia Molecular Dirigida , Conformación Proteica , Subunidades de Proteína/química , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Proteínas RGS/clasificación , Proteínas RGS/genética , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Lesbian, gay, bisexual, transgender, queer, intersex, and asexual/aromantic (LGBTQIA+) providers improve health outcomes of sexual and gender minority (SGM) patients, which demonstrates the importance of understanding the state of LGBTQIA+ representation at all levels of medical training. The U.S. does not systematically collect sexual orientation and gender identity (SOGI) data from applicants, trainees, and attending physicians, prompting us to wonder whether SGM representation in surgical fields, such as otolaryngology, is adequate. Personal statements submitted to an otolaryngology program from 2019 to 2021 were searched for LGBTQIA+ terms, and those containing LGBTQIA+ terms underwent full text review to determine whether applicants identified themselves as LGBTQIA+. Across these 2 application cycles, the sampled residency program received 928 applications. Only 2 applicants of 928 (0.2%) self-disclosed their LGBTQIA+ identities in their personal statements. These results signify a scarcity of SGM diversity in otolaryngology and warrant deeper exploration into factors preventing residency applicants from self-disclosure of LGBTQIA+ identities.
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Internado y Residencia , Otolaringología , Minorías Sexuales y de Género , Humanos , Otolaringología/educación , Femenino , Masculino , Estados UnidosRESUMEN
OBJECTIVE: While evidence continues to emerge on the negative health effects of electronic cigarettes (e-cigarettes) on the lungs, little is known regarding their deleterious effects on the upper airway. The purpose of this review is to summarize the toxicological effects of e-cigarettes, and their components, on the upper airway. DATA SOURCES: PubMed, SCOPUS, EMBASE databases. REVIEW METHODS: Systematic searches were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from 2003 to 2023. Studies were included if they investigated the toxicological effects of e-cigarette exposure on human or animal upper airway tissue. Two authors independently screened, reviewed, and appraised all included articles. RESULTS: A total of 822 unique articles were identified, of which 53 met inclusion criteria and spanned subsites including the oral cavity (22/53 studies), nasal cavity/nasopharynx (13/53), multiple sites (10/53), larynx (5/53), trachea (2/53), and oropharynx (1/53). The most commonly observed consequences of e-cigarette use on the upper airway included: proinflammatory (15/53 studies), histological (13/53), cytotoxicity (11/53), genotoxicity (11/53), and procarcinogenic (6/53). E-cigarette humectants independently induced toxicity at multiple upper airway subsites, however, effects were generally amplified when flavoring(s) and/or nicotine were added. Across almost all studies, exposure to cigarette smoke exhibited increased toxicity in the upper airway compared with exposure to e-cigarette vapor. CONCLUSION: Current data suggest that while e-cigarettes are generally less harmful than traditional cigarettes, they possess a distinct toxicological profile that is enhanced upon the addition of flavoring(s) and/or nicotine. Future investigations into underexamined subsites, such as the oropharynx and hypopharynx, are needed to comprehensively understand the effects of e-cigarettes on the upper airway.
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Sistemas Electrónicos de Liberación de Nicotina , Animales , Humanos , Sistema Respiratorio/efectos de los fármacos , Vapeo/efectos adversosRESUMEN
BACKGROUND: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. METHODS: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre-operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra-operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. RESULTS: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. CONCLUSIONS: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1551-1555, 2024.
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Rinitis Alérgica , Rinitis , Sinusitis , Humanos , Fluticasona/uso terapéutico , Cavidad Nasal , Rinitis Alérgica/cirugía , Rinitis Alérgica/tratamiento farmacológico , Sinusitis/cirugía , Sinusitis/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Seno Maxilar , Enfermedad Crónica , Rinitis/cirugíaRESUMEN
A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.
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Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Cadáver , Hueso Etmoides , Cavidad Nasal/cirugíaRESUMEN
KEY POINTS: Primary ciliary dyskinesia (PCD) is a complex diagnosis without a universal diagnostic test Clinicians must have some skepticism of historic diagnoses of PCD Clinicians should consider a diagnosis of PCD in patients with recalcitrant disease.
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Trastornos de la Motilidad Ciliar , Síndrome de Kartagener , Humanos , Trastornos de la Motilidad Ciliar/diagnóstico , Síndrome de Kartagener/diagnósticoRESUMEN
BACKGROUND: Priming is a psychological phenomenon where subconscious cues in the environment impact our behavioral responses in certain situations. Well studied in the worlds of business, marketing, and even politics, it is unclear how the priming phenomenon impacts patient perception of their own disease state nor how they report that perception using tools like the Sinonasal Outcomes Test (SNOT-22), used to measure that perception in chronic rhinosinusitis. OBJECTIVE: To determine the impact of positive or negative priming on self-reported patient perception of their chronic rhinosinusitis disease using the SNOT-22 disease-specific quality of life instrument. METHODS: Single-blind, randomized, prospective cohort pilot study of 206 consecutive adult patients with a clinical diagnosis of chronic rhinosinusitis presenting to a university rhinology clinic. Patients were randomized to receive "positive priming" (103) or "negative priming" (103) by reading a passage about the positive or negative aspects of chronic sinusitis and its treatment respectively. Patients were then asked to fill out the SNOT-22 and results between the two groups were compared. RESULTS: The negative priming group had a higher median SNOT-22 score of 49 [IQR = 39] compared to the positive priming groups' score of 22 [IQR = 27], p < 0.0001), a difference of nearly three times the minimal clinical impactful difference (MCID). This effect was consistent regardless of age or sex of the patient. Subgroup analysis revealed a greater impact when priming was performed by the senior male attending regardless of patient age or sex (p < 0.001), while priming performed by the younger female research fellow had greater impact on older patients (>59 years, p = 0.001) and female patients (p = 0.003). CONCLUSIONS: Priming impacts how patient's perceive their chronic rhinosinusitis as determined by the SNOT-22. It is imperative that the rhinologist understand this when using this instrument in research applications and in clinical decision-making for patients.
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Rinitis , Sinusitis , Adulto , Humanos , Masculino , Femenino , Prueba de Resultado Sino-Nasal , Estudios Prospectivos , Calidad de Vida , Proyectos Piloto , Método Simple Ciego , Rinitis/diagnóstico , Rinitis/terapia , Sinusitis/diagnóstico , Sinusitis/terapia , Enfermedad CrónicaRESUMEN
KEY POINTS: All intranasal corticosteroid spray formulations are safe to use in patients on pre-exposure prophylaxis. Beclomethasone nasal spray can be used safely with all HAART and PrEP regimens.
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Administración Intranasal , Corticoesteroides , Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Beclometasona/administración & dosificación , Beclometasona/uso terapéutico , Rociadores NasalesRESUMEN
KEY POINTS: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.
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Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.
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KEY POINTS: Automated plagiarism-checking software can be a valuable tool for detecting plagiarism in manuscripts. Twenty-five of 60 articles (42%) had at least one incidence of plagiarism, predominately text recycling. A "similarity score" ranging from 22% to 35% could be a potential cut-off value when screening submitted manuscripts.
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Publicaciones Periódicas como Asunto , Plagio , Humanos , Otolaringología , Programas InformáticosRESUMEN
The goal of this American Rhinologic Society Expert Practice Statement (EPS) is to provide recommendations and guidance through evidence-based consensus statements regarding pediatric septoplasty. This EPS was developed following the previously published methodology and approval process. The topics of interest included appropriate indications, safety and efficacy, timing, relevant quality of life instruments, and surgical techniques. Following a modified Delphi approach, six statements were developed, five of which reached consensus and one that did not. These statements and accompanying evidence are summarized along with an assessment of future needs.