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Little is known about the relationships between symptomatic early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate coronavirus disease 19 (COVID-19). We measured SARS-CoV-2 viral load using reverse transcription-quantitative PCR (RT-qPCR). We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 95% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited codetection of other respiratory viruses, with the human Rhinovirus C being identified in 4 (6%) samples. This limited codetection of other respiratory viral pathogens may be due to the implementation of public health measures, like social distancing and masking practices. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusting for age, sex, and race. Interestingly, the expression levels of most of these genes plateaued at a cycle threshold (CT) value of ~25. Overall, our data show that the early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, potentially modifying COVID-19 outcomes. IMPORTANCE Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load, airway mucosal gene expression, and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load, interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load dependent and may modify COVID-19 outcomes.
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COVID-19 , Expresión Génica , Mucosa Respiratoria , SARS-CoV-2 , Carga Viral , Adulto , Humanos , Quimiocinas/fisiología , COVID-19/inmunología , COVID-19/virología , Expresión Génica/inmunología , Inmunidad Mucosa/inmunología , Interferones/fisiología , SARS-CoV-2/genética , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/virologíaRESUMEN
BACKGROUND: Little is known about the relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the respiratory virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, and the upper respiratory tract (URT) microbiome. OBJECTIVE: We sought to compare the URT microbiome between SARS-CoV-2-infected and -uninfected adults and to examine the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19. METHODS: We characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild to moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using quantitative reverse transcription PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the âº-diversity, ß-diversity, and abundance of bacterial taxa of the URT microbiome. Our main models were all adjusted for age and sex. RESULTS: The observed species index was significantly higher in SARS-CoV-2-infected than in -uninfected adults (ß linear regression coefficient = 7.53; 95% CI, 0.17-14.89; P = .045). In differential abundance testing, 9 amplicon sequence variants were significantly different in both of our comparisons, with Peptoniphilus lacrimalis, Campylobacter hominis, Prevotella 9 copri, and an Anaerococcus unclassified amplicon sequence variant being more abundant in those with SARS-CoV-2 infection and in those with high viral load during COVID-19, whereas Corynebacterium unclassified, Staphylococcus haemolyticus, Prevotella disiens, and 2 Corynebacterium_1 unclassified amplicon sequence variants were more abundant in those without SARS-CoV-2 infection and in those with low viral load during COVID-19. CONCLUSIONS: Our findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Future studies are needed to examine how these viral-bacterial interactions can impact the clinical progression, severity, and recovery of COVID-19.
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COVID-19/microbiología , COVID-19/virología , Microbiota , Sistema Respiratorio/microbiología , SARS-CoV-2 , Carga Viral , Adulto , Biodiversidad , Estudios de Casos y Controles , Femenino , Interacciones Microbiota-Huesped , Humanos , Masculino , Microbiota/genética , Persona de Mediana Edad , Pandemias , ARN Ribosómico 16S/genética , Especificidad de la EspecieRESUMEN
INTRODUCTION: Persistent tympanic membrane perforation is a known complication of pressure-equalizing (PE) tube insertion. Conductive hearing loss and otorrhea can necessitate surgical repair of these perforations. Long-term tympanostomy tube placement can increase the risk of these complications. Patients with velocardiofacial syndrome (VCFS) typically require prolonged PE tube placement and are thought to have higher risk of requiring additional otologic interventions after PE tube placement. To date, no work has established rates of post-PE tube complications requiring myringoplasty or tympanoplasty in patients with VCFS. METHODS: A retrospective case review including all patients with VCFS at a single large children's hospital between the years 2000 and 2020 was performed. Number of PE tube insertions required and additional otologic interventions performed were the primary endpoints assessed. RESULTS: Of 212 total patients with VCFS, 66 (31%) underwent PE tube placement. Of these children, 46 (70%) required 2 or more sets of PE tubes. A total of 53 patients (80.3%) required no otologic interventions apart from PE tube insertions. Of the 13 patients (19.7%) requiring additional otologic surgery, 6 (9.5%) underwent myringoplasty, and 9 patients (13.6%) required tympanoplasty. There was no significant difference in tympanoplasty (P > 1), myringoplasty (P > 1), or other surgical intervention rates (P = .7464) between VCFS patients with any type of cleft palate versus those with anatomically normal palates. CONCLUSION: This work suggests that most VCFS patients that require tubes, require at least 2 sets of PE tubes, and that the rate of post-PE tube complications requiring further otologic surgery is an order of magnitude higher than the rate established at this institution. Counseling for PE tube placement in VCFS patients may require specific dialogue regarding the substantially increased risk of complications and effort to build appropriate expectations for surgical outcomes regardless of palatal status.
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Fisura del Paladar , Síndrome de DiGeorge , Niño , Humanos , Síndrome de DiGeorge/complicaciones , Síndrome de DiGeorge/cirugía , Estudios Retrospectivos , Miringoplastia/efectos adversos , Timpanoplastia/efectos adversos , Fisura del Paladar/cirugía , Ventilación del Oído Medio/efectos adversosRESUMEN
OBJECTIVE: Comparison of outcomes of microscopic and endoscopic resection of glomus tympanicum (GT) tumors. STUDY DESIGN: Retrospective case review. SETTING: Single tertiary referral center. PATIENTS: All adult patients undergoing transcanal GT resection without mastoidectomy from 2007 to 2021. INTERVENTIONS: Surgical resection-endoscopic versus microscopic approach. MAIN OUTCOME MEASURES: Primary outcomes were tumor recurrence at 1 year and presence of residual tumor at conclusion of surgery. Secondary outcome measures included operative time, postoperative air-bone gap, postoperative symptom resolution, and surgical complications. RESULTS: Thirty-eight patients underwent resection of GT (74% female; mean age, 59 years). Twenty-nine cases were performed microscopically, and nine cases were performed endoscopically. Both endoscopic and microscopic approaches yielded high rates of complete tumor resection (27/29 microscopic cases, 7/9 endoscopic cases). There was no significant difference in mean operative time (2.3 hours for microscopic; 2.6 hours for endoscopic). On average, air-bone gaps (ABGs) decreased by 6.3 dB after endoscopic resection compared with 1.0 dB after microscopic resection ( p = 0.064). No patients were found to have tumor recurrence during an average follow-up interval of 21 months. CONCLUSIONS: These results suggest comparable outcomes with both endoscopic and microscopic approaches for GT resection, and decisions regarding preferred approach should be dictated by surgeon preference.
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Glomo Timpánico , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Resultado del Tratamiento , Endoscopía/métodosRESUMEN
OBJECTIVE: To report speech recognition outcomes and processor use based on timing of cochlear implant (CI) activation. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: A total of 604 adult CI recipients from October 2011 to March 2022, stratified by timing of CI activation (group 1: ≤10 d, n = 47; group 2: >10 d, n = 557). MAIN OUTCOME MEASURES: Average daily processor use; Consonant-Nucleus-Consonant (CNC) and Arizona Biomedical (AzBio) in quiet at 1-, 3-, 6-, and 12-month visits; time to peak performance. RESULTS: The groups did not differ in sex ( p = 0.887), age at CI ( p = 0.109), preoperative CNC ( p = 0.070), or preoperative AzBio in quiet ( p = 0.113). Group 1 had higher median daily processor use than group 2 at the 1-month visit (12.3 versus 10.7 h/d, p = 0.017), with no significant differences at 3, 6, and 12 months. The early activation group had superior median CNC performance at 3 months (56% versus 46%, p = 0.007) and 12 months (60% versus 52%, p = 0.044). Similarly, the early activation group had superior median AzBio in quiet performance at 3 months (72% versus 59%, p = 0.008) and 12 months (75% versus 68%, p = 0.049). Both groups were equivalent in time to peak performance for CNC and AzBio. Earlier CI activation was significantly correlated with higher average daily processor use at all follow-up intervals. CONCLUSION: CI activation within 10 days of surgery is associated with increased early device usage and superior speech recognition at both early and late follow-up visits. Timing of activation and device usage are modifiable factors that can help optimize postoperative outcomes in the CI population.
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Implantación Coclear , Implantes Cocleares , Percepción del Habla , Adulto , Humanos , Estudios Retrospectivos , Percepción del Habla/fisiología , Habla , Resultado del TratamientoRESUMEN
Introduction The middle fossa craniotomy (MFCs) is commonly utilized for spontaneous cerebrospinal fluid (CSF) leaks, encephaloceles, and superior semicircular canal dehiscence (SSCD). This study compares postoperative outcomes of MFCs with and without LD use. Methods A retrospective cohort study of adults over the age of 18 years presenting for the repair of nonneoplastic CSF leak, encephalocele, or SSCD via MFC from 2009 to 2021 was conducted. The main exposure of interest was the placement of an LD. The primary outcome was the presence of postoperative complications (acute/delayed neurologic deficit, meningitis, intracranial hemorrhage, and stroke). Secondary outcomes included operating room (OR) time, length of stay, recurrence, and need for reoperation. Results In total, 172 patients were included, 96 of whom received an LD and 76 who did not. Patients not receiving an LD were more likely to receive intraoperative mannitol ( n = 24, 31.6% vs. n = 16, 16.7%, p = 0.02). On univariate logistic regression, LD placement did not influence overall postoperative complications (OR: 0.38, 95% confidence interval [CI]: 0.05-2.02, p = 0.28), CSF leak recurrence (OR: 0.75, 95% CI: 0.25-2.29, p = 0.61), or need for reoperation (OR: 1.47, 95% CI: 0.48-4.96, p = 0.51). While OR time was shorter for patients not receiving LD (349 ± 71 vs. 372 ± 85 minutes), this difference was not statistically significant ( p = 0.07). Conclusion No difference in postoperative outcomes was observed in patients who had an intraoperative LD placed compared to those without LD. Operative times were increased in the LD cohort, but this difference was not statistically significant. Given the similar outcomes, we conclude that LD is not necessary to facilitate safe MCF for nonneoplastic skull base pathologies.
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First-generation amperometric glucose biosensors incorporating alkanethiolate-protected gold nanoparticles, monolayer protected clusters (MPCs), within a xerogel matrix are investigated as model systems for nanomaterial-assisted electrochemical sensing strategies. The xerogel biosensors are comprised of platinum electrodes modified with composite films of (3-mercaptopropyl)trimethoxy silane xerogel embedded with glucose oxidase enzyme, doped with Au225(C6)75 MPCs, and coated with an outer polyurethane layer. Electrochemistry and scanning/transmission electron microscopy, including cross-sectional TEM, show sensor construction, humidity effects on xerogel structure, and successful incorporation of MPCs. Analytical performance of the biosensor scheme with and without MPC doping of the xerogel is determined from direct glucose injection during amperometry. MPC-doped xerogels yield significant enhancement of several sensor attributes compared to analogous films without nanoparticles: doubling of the linear range, sensitivity enhancement by an order of magnitude, and 4-fold faster response times accompany long-term stability and resistance to common interfering agents that are competitive with current glucose biosensing literature. Ligand chain length and the MPC/silane ratio studies suggest the MPC-induced enhancements are critically related to structure-function relationships, particularly those affecting interparticle electronic communication where the MPC network behaves as a three-dimensional extension of the working electrode into the xerogel film, reducing the system's dependence on diffusion and maximizing efficiency of the sensing mechanism. The integration of MPCs as a functional component of amperometric biosensor schemes has implications for future development of biosensors targeting clinically relevant species.
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Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Glucosa/análisis , Oro/química , Nanopartículas del Metal/química , Adsorción , Calibración , Electrodos , Geles , Glucosa Oxidasa/química , Membranas Artificiales , Transición de Fase , Platino (Metal) , Poliuretanos , Silanos , SolucionesRESUMEN
OBJECTIVE: Microvascular free tissue transfer is an important reconstructive option for defects of the head and neck. The present study aims to identify preoperative patient- and tumor-specific characteristics, laboratory values, and other risk factors associated with early free flap failure. STUDY DESIGN: Retrospective cohort study of 1070 patients. SETTING: Head and neck surgical oncology service at a tertiary care center from 2005 to 2019. METHODS: Demographics, comorbidities, preoperative laboratory values, treatment history, and cancer stage were collected for consecutive patients who underwent free flap reconstruction of the head and neck and experienced early free flap failure (<8 days from surgery). RESULTS: In 1070 patients, the prevalence of early free flap failure was 3.8% (n = 41). Female sex (odds ratio [OR], 2.58; 95% CI, 1.36-4.99), presence of peripheral vascular disease (OR, 2.78; 95% CI, 1.05-6.57), and elevated preoperative platelet count (OR, 2.67; 95% CI, 1.20-5.47) were independently associated with risk of early free flap failure. CONCLUSION: Female sex, peripheral vascular disease, and preoperative thrombocytosis are all strong predictors of early free flap failure. This suggests that hypercoagulability and poor vessel quality may predispose patients to flap loss. Patients with elevated platelets or peripheral vascular disease warrant careful reconstructive decision making and close monitoring in the perioperative period.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Procedimientos de Cirugía Plástica , Humanos , Femenino , Colgajos Tisulares Libres/irrigación sanguínea , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/complicaciones , Cuello/cirugía , Complicaciones Posoperatorias/etiologíaRESUMEN
TITLE: Facial Paralysis in Skull Base Osteomyelitis - Comparison of Surgical and Nonsurgical Management. OBJECTIVE: To compare outcomes of surgical and nonsurgical management in cases of facial paresis secondary to skull base osteomyelitis. METHODS: A 14 patients presenting with skull base osteomyelitis complicated by facial nerve paresis at a single tertiary referral center from 2009 to 2019 were retrospectively reviewed. Patients were treated with medical therapy with or without surgical intervention, consisting of mastoidectomy and debridement with or without facial nerve decompression. House-Brackmann (HB) Grade was the main outcome measure. RESULTS: A 14 patients (average age 68 years, range 58-82 years, 71% male) were analyzed, with 5 undergoing facial nerve decompression (36%), 5 undergoing mastoidectomy without facial nerve decompression (36%), and 4 undergoing medical management alone (28%). Of the 4 patients who underwent medical therapy alone, none experienced significant improvement in facial function. Of the 5 patients who underwent facial nerve decompression, 3 patients experienced improved facial function. Of the 5 patients who underwent mastoidectomy without decompression, 4 experienced improved facial function. There was no clear link between the severity of infection and the severity of facial paresis. When comparing HB score changes before and after treatment across groups, there was no statistically significant difference seen (p = 0.47). CONCLUSIONS: Mastoidectomy and debridement with or without facial nerve decompression may improve facial nerve outcomes when compared to isolated medical management, although differences were not of statistical significance. The best facial nerve recoveries occurred in patients undergoing surgery within 14 days of the onset of paralysis. LEVEL OF EVIDENCE: 4 - Case Series Laryngoscope, 133:179-183, 2023.
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Parálisis Facial , Osteomielitis , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Parálisis Facial/etiología , Parálisis Facial/cirugía , Estudios Retrospectivos , Nervio Facial/cirugía , Base del Cráneo/cirugía , Osteomielitis/complicaciones , Osteomielitis/cirugía , Descompresión Quirúrgica , Resultado del TratamientoRESUMEN
OBJECTIVE: To characterize the incidence of sigmoid sinus occlusion (SSO) following translabyrinthine (TL) surgery for posterior fossa tumor resection and determine the association with cerebrospinal fluid (CSF) leak. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. METHODS: Patients undergoing TL surgery for vestibular schwannoma from 2012 to 2020 were included. Demographic data, medical history, preoperative tumor length and volume, and postoperative complications including CSF leak were recorded. Neuroradiology review of postoperative magnetic resonance imaging was used to determine the presence or absence of flow through the sigmoid sinus. RESULTS: Of 205 patients undergoing TL, 21 (10.2%) experienced CSF leak postoperatively. Overall 56 (27%) demonstrated SSO on immediate postoperative magnetic resonance imaging. CSF leaks were more likely in those with SSO (19.6%) than those without SSO (6.7%; odds ratio, 3.54 [95% CI, 1.25-10.17]). Tumor volume and body mass index were not significantly associated with CSF leak. In total, 105 (51%) patients had some degree of sigmoid sinus thrombosis, but nonocclusive thrombosis was not associated with CSF leak. CONCLUSION: SSO after TL approaches is common and appears to be significantly associated with postoperative CSF leak development. Minimizing manipulation of the sigmoid sinus during TL surgery and compression after surgery may have a role in preventing CSF leak.
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Pérdida de Líquido Cefalorraquídeo , Neuroma Acústico , Humanos , Estudios Retrospectivos , Pérdida de Líquido Cefalorraquídeo/epidemiología , Pérdida de Líquido Cefalorraquídeo/etiología , Neuroma Acústico/cirugía , Neuroma Acústico/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Índice de Masa CorporalRESUMEN
To date, little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, on the upper respiratory tract (URT) microbiota over time. To fill this knowledge gap, we used 16S ribosomal RNA gene sequencing to characterize the URT microbiota in 48 adults, including (1) 24 participants with mild-to-moderate COVID-19 who had serial mid-turbinate swabs collected up to 21 days after enrolment and (2) 24 asymptomatic, uninfected controls who had mid-turbinate swabs collected at enrolment only. To compare the URT microbiota between groups in a comprehensive manner, different types of statistical analyses that are frequently employed in microbial ecology were used, including âº-diversity, ß-diversity and differential abundance analyses. Final statistical models included age, sex and the presence of at least one comorbidity as covariates. The median age of all participants was 34.00 (interquartile range=28.75-46.50) years. In comparison to samples from controls, those from participants with COVID-19 had a lower observed species index at day 21 (linear regression coefficient=-13.30; 95â% CI=-21.72 to -4.88; q=0.02). In addition, the Jaccard index was significantly different between samples from participants with COVID-19 and those from controls at all study time points (PERMANOVA q<0.05 for all comparisons). The abundance of three amplicon sequence variants (ASVs) (one Corynebacterium ASV, Frederiksenia canicola, and one Lactobacillus ASV) were decreased in samples from participants with COVID-19 at all seven study time points, whereas the abundance of one ASV (from the family Neisseriaceae) was increased in samples from participants with COVID-19 at five (71.43â%) of the seven study time points. Our results suggest that mild-to-moderate COVID-19 can lead to alterations of the URT microbiota that persist for several weeks after the initial infection.
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COVID-19 , Microbiota , Humanos , Adulto , Persona de Mediana Edad , SARS-CoV-2 , Sistema RespiratorioRESUMEN
OBJECTIVE: To quantify the effect of datalogging on speech recognition scores and time to achievement for a "benchmark" level of performance within the first year, and to provide a data-driven recommendation for minimum daily cochlear implant (CI) device usage to better guide patient counseling and future outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: Three hundred thirty-seven adult CI patients with data logging and speech recognition outcome data who were implanted between August 2015 and August 2020. MAIN OUTCOME MEASURES: Processor datalogging, speech recognition scores, achievement of "benchmark speech recognition performance" defined as 80% of the median score for speech recognition outcomes at our institution. RESULTS: The 1-month datalogging measure correlated positively with word and sentences scores at 1, 3, 6, and 12 months postactivation. Compared with age, sex, and preoperative performance, datalogging was the largest predictive factor of benchmark achievement on multivariate analysis. Each hour/day increase of device usage at 1 month resulted in a higher likelihood of achieving benchmark consonant-nucleus-consonant and AzBio scores within the first year (odds ratio = 1.21, p < 0.001) as well as earlier benchmark achievement. Receiver operating characteristic curve analysis identified the optimal data logging threshold at an average of 12 hours/day. CONCLUSIONS: Early CI device usage, as measured by 1-month datalogging, predicts benchmark speech recognition achievement in adults. Datalogging is an important predictor of CI performance within the first year postimplantation. These data support the recommended daily CI processor utilization of at least 12 hours/day to achieve optimal speech recognition performance for most patients.
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Implantación Coclear , Implantes Cocleares , Percepción del Habla , Adulto , Humanos , Estudios Retrospectivos , Percepción del Habla/fisiología , Implantación Coclear/métodos , Lenguaje , Resultado del TratamientoRESUMEN
BACKGROUND: This work seeks to better understand the triage strategies employed by head and neck oncologic surgical divisions during the initial phases of the coronavirus 2019 (COVID-19) outbreak. METHODS: Thirty-six American head and neck surgical oncology practices responded to questions regarding the triage strategies employed from March to May 2020. RESULTS: Of the programs surveyed, 11 (31%) had official department or hospital-specific guidelines for mitigating care delays and determining which surgical cases could proceed. Seventeen (47%) programs left the decision to proceed with surgery to individual surgeon discretion. Five (14%) programs employed committee review, and 7 (19%) used chairman review systems to grant permission for surgery. Every program surveyed, including multiple in COVID-19 outbreak epicenters, continued to perform complex head and neck cancer resections with free flap reconstruction. CONCLUSIONS: During the initial phases of the COVID-19 pandemic experience in the United States, head and neck surgical oncology divisions largely eschewed formal triage policies and favored practices that allowed individual surgeons discretion in the decision whether or not to operate. Better understanding the shortcomings of such an approach could help mitigate care delays and improve oncologic outcomes during future outbreaks of COVID-19 and other resource-limiting events. LEVEL OF EVIDENCE: 4.
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COVID-19 , Neoplasias de Cabeza y Cuello , Oncología Quirúrgica , Estados Unidos/epidemiología , Humanos , Pandemias/prevención & control , Triaje , SARS-CoV-2 , Neoplasias de Cabeza y Cuello/cirugíaRESUMEN
OBJECTIVE: Demonstrate the ability of a novel steerable distal chip endoscope to traverse the Eustachian tube and provide diagnostic quality images of the human middle ear. PATIENTS: Three cadaveric temporal bone specimens were used in this work. INTERVENTION: Diagnostic transeustachian endoscopy of the middle ear was performed. MAIN OUTCOME MEASURE: Diagnostic image quality. RESULTS: A novel 1.62âmm steerable endoscope successfully cannulated the Eustachian tube of three human cadaveric temporal bone specimens to reveal intact middle ear anatomy with high optical clarity. CONCLUSIONS: A steerable endoscope can be designed to traverse the human Eustachian tube and provide diagnostic quality images of middle ear anatomy.
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Oído Medio , Trompa Auditiva , Cadáver , Oído Medio/anatomía & histología , Oído Medio/diagnóstico por imagen , Oído Medio/cirugía , Endoscopios , Endoscopía/métodos , Trompa Auditiva/diagnóstico por imagen , Trompa Auditiva/cirugía , HumanosRESUMEN
Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARY: Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.
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BACKGROUND: The nose is the portal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, suggesting the nose as a target for topical antiviral therapies. The purpose of this study was to assess both the in vivo and in vitro efficacy of a detergent-based virucidal agent, Johnson and Johnson's Baby Shampoo (J&J), in SARS-CoV-2-infected subjects. METHODS: Subjects were randomized into three treatment groups: (1) twice daily nasal irrigation with J&J in hypertonic saline, (2) hypertonic saline alone, and (3) no intervention. Complementary in vitro experiments were performed in cultured human nasal epithelia. The primary outcome measure in the clinical trial was change in SARS-CoV-2 viral load over 21 days. Secondary outcomes included symptom scores and change in daily temperature. Outcome measures for in vitro studies included change in viral titers. RESULTS: Seventy-two subjects completed the clinical study (n = 24 per group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. CONCLUSION: In this randomized clinical trial of subjects with SARS-CoV-2 infection, a topical detergent-based virucidal agent had no effect on viral load or symptom scores. Complementary in vitro studies confirmed a lack of efficacy, reflective of pharmacokinetic failure and rapid absorption from nasal surfaces.
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COVID-19 , Resfriado Común , Antivirales , Detergentes , Humanos , SARS-CoV-2 , Carga ViralRESUMEN
The objective of this paper is to describe the development of a minimally invasive cochlear implant surgery (MICIS) electrode array insertion tool concept to enable clinical translation. First, analysis of the geometric parameters of potential MICIS patients (N = 97) was performed to inform tool design, inform MICIS phantom model design, and provide further insight into MICIS candidacy. Design changes were made to the insertion tool based on clinical requirements and parameter analysis results. A MICIS phantom testing model was built to evaluate insertion force profiles in a clinically realistic manner, and the new tool design was evaluated in the model and in cadavers to test clinical viability. Finally, after regulatory approval, the tool was used for the first time in a clinical case. Results of this work included first, in the parameter analysis, approximately 20% of the population was not considered viable MICIS candidates. Additionally, one 3D printed tool could accommodate all viable candidates with polyimide sheath length adjustments accounting for interpatient variation. The insertion tool design was miniaturized out of clinical necessity and a disassembly method, necessary for removal around the cochlear implant, was developed and tested. Phantom model testing revealed that the force profile of the insertion tool was similar to that of traditional forceps insertion. Cadaver testing demonstrated that all clinical requirements (including complete disassembly) were achieved with the tool, and the new tool enabled 15% deeper insertions compared to the forceps approach. Finally, and most importantly, the tool helped achieve a full insertion in its first MICIS clinical case. In conclusion, the new insertion tool provides a clinically viable solution to one of the most difficult aspects of MICIS.
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OBJECTIVE/HYPOTHESIS: Mortality attribution can have significant implications for reimbursement, hospital/department rankings, and perceptions of safety. This work seeks to compare the accuracy of externally assigned diagnosis-related group (DRG)-based service line mortality attribution in otolaryngology to an internal review process that assigns mortality to the teams that cared for a patient during hospitalization. STUDY DESIGN: Retrospective case series. METHODS: Mortality events at Vanderbilt University Medical Center (VUMC) from 2012 to 2018 were compared. Included events were assigned to the otolaryngology service line (OSL) via the following methods: an external agency (Vizient) using DRG, utilization management assignment based on the service that provided care at admission (admission service), discharge (discharge service), or throughout hospitalization (major service line), or through the internal VUMC mortality review committee. Internal review was considered the standard for comparison. RESULTS: Of the 28 mortality events assigned to OSL by the DRG-based external method, nine (32%) were actually attributable to OSL. Of the 23 total mortality events attributable to OSL at our institution, external DRG-based review captured nine (39%). The designation of major service during hospitalization was correct 95% of the time and captured 87% of mortality events. Differences between external and internal attribution methods were statistically significant (P < .001). CONCLUSIONS: DRG-based models are frequently utilized but can be inaccurate when attributing mortality for an individual otolaryngology department. Otolaryngology mortalities appear to be captured and assigned more accurately by assigning deaths to the service that renders the majority of care during hospitalization. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1805-E1810, 2021.
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Grupos Diagnósticos Relacionados , Mortalidad Hospitalaria , Otolaringología/normas , Enfermedades Otorrinolaringológicas/mortalidad , Evaluación de Resultado en la Atención de Salud , Grupo de Atención al Paciente/normas , Humanos , Estudios Retrospectivos , TennesseeRESUMEN
Background: The upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited. Objective: Our primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity. Methods: Using data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19. Results: URT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased. Conclusions: We observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.
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COVID-19 , Microbiota , Adulto , Bacterias , Humanos , Sistema Respiratorio , SARS-CoV-2RESUMEN
The nose is the portal for SARS-CoV-2 infection, suggesting the nose as a target for topical antiviral therapies. Because detergents are virucidal, Johnson and Johnson's Baby Shampoo (J&J) was tested as a topical virucidal agent in SARS-CoV-2 infected subjects. Twice daily irrigation of J&J in hypertonic saline, hypertonic saline alone, or no intervention were compared (n = 24/group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. This study emphasizes the need to assess the pharmacokinetic characteristics of virucidal agents on airway surfaces to guide clinical trials.