Mucosal Gene Expression in Response to SARS-CoV-2 Is Associated with Viral Load.

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.

Rhinoplasty Outcomes in Patients With Symptoms of Body Dysmorphia.

BACKGROUND: Patients with symptoms of body dysmorphia often seek consultation for aesthetic rhinoplasty. While body dysmorphic disorder is a formal psychiatric diagnosis, recent evidence indicates that patients with symptoms of this condition who seek rhinoplasty may experience increased satisfaction with their appearance following surgery. OBJECTIVES: To determine the psychological impact of rhinoplasty in patients screened preoperatively and postoperatively with a body dysmorphia screening questionnaire. METHODS: Retrospective chart review was performed of patients who underwent aesthetic and/or functional rhinoplasty by a single surgeon from June 2021 to April 2023. Adult patients with a complete preoperative and postoperative Body Dysmorphic Disorder-Aesthetic Surgery questionnaire (BDDQ-AS), Standardized Cosmesis and Health Nasal Outcomes Survey-Obstruction and Cosmesis (SCHNOS), and visual analog scale (VAS) were included. Patient characteristics and outcomes were analyzed, stratifying by BDDQ-AS screen. RESULTS: One-hundred fifteen patients (88% female) met criteria for inclusion. There was an 83% resolution rate of BDDQ-AS positive screening following rhinoplasty. Positive BDDQ-AS screening status preoperatively and postoperatively correlated with worse aesthetic satisfaction (all P < .002). No patient-reported outcome measures were indicative of which patients with a BDDQ-AS positive screen preoperatively would experience "resolution" postoperatively. CONCLUSIONS: Body dysmorphia screening resolution following surgical intervention correlated with improved patient aesthetic satisfaction, pointing to a potential positive psychological impact of undergoing rhinoplasty.

Evidence-Based Medicine: Rhinoplasty Surgical Outcomes.

Evidence-based medicine has become increasingly important in healthcare today by providing a process to examine the highest levels of research and apply them to clinical practice. Integrating the best available evidence to clinical decision making ensures that patients receive the highest level of care based on thoroughly reviewed and validated research. These concepts can also be applied to rhinoplasty, both aesthetic and functional, emphasizing the importance of data-driven decisions to improve clinical care.

Evidence-Based Medicine: Facial Reanimation.

This article provides a brief historical overview of the assessment instruments that have been developed to categorize the severity of disease in patients with facial palsy. Important advances in the quality of these instruments are discussed. The modern-day instruments that are commonly required for evidence-based patient assessment are then presented, with emphasis on the level of evidence of the studies that describe these instruments.

SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome.

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 ⍺-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.

Repair of Septal Perforations.

Nasal septal perforations have varied etiologies, clinical presentations, and methods of management. Some patients may be asymptomatic, while others may complain of nasal obstruction, crusting, epistaxis, and whistling. Management of nasal septal perforations is guided by the patient's symptoms and characteristics of the perforation. Some lesions can be managed conservatively or with minimally invasive procedures, while others require surgery. Surgical repair of perforations can be challenging and many techniques have been described without a standardized method of management. This article aims to provide a comprehensive review of options for repair of nasal septal perforations.

Incidence and Outcomes of Acute Laryngeal Injury After Prolonged Mechanical Ventilation.

OBJECTIVES: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes. DESIGN: Prospective cohort study. SETTING: Tertiary referral critical care center. PATIENTS: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation. INTERVENTIONS: Laryngoscopy following endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury. CONCLUSIONS: Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.

Patient Outcomes in Lateral Crural Repositioning and Reconstruction in Revision Rhinoplasty.

Background: In revision rhinoplasty, lateral crural repositioning/reconstruction is considered a complex maneuver. The aim of this study is to measure patient outcomes after lateral crural repositioning/reconstruction in revision rhinoplasty. Methods: In this retrospective case series, patients who underwent revision rhinoplasty with lateral crural repositioning/reconstruction for functional, cosmetic, or combined purposes were reviewed. Preoperative Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) scores, functional and cosmetic visual analog scales (VAS-functional [F] and VAS-cosmetic [C]), and lateral wall insufficiency (LWI) grades were compared with their respective postoperative scores. Results: Forty-two patients were identified who underwent lateral crural repositioning. The mean postoperative follow-up for ≤6 months (PO1) and >6 months (PO2) was 3.1 (standard deviation [SD] 1.7) and 11.5 (SD 5.3) months, respectively. At both postoperative periods, significant improvement (p < 0.05) in patient-reported outcomes was observed in mean SCHNOS-Obstruction, SCHNOS-Cosmesis, VAS-F, and VAS-C scores. The postoperative changes in LWI scores (Δ) were significant on both sides at zone 1 at PO1 (p < 0.05) and PO2 (p < 0.05), and at PO2 on the left side (p < 0.05) only, for zone 2. Conclusion: Lateral crural repositioning with reconstruction is an effective maneuver in revision rhinoplasty in a subset of patients and specifically helps to improve nasal tip aesthetics while preserving function.

Forehead Flap Practices: A Cross-Sectional Survey of Facial Plastic and Reconstructive Surgeons.

Background: The paramedian forehead flap (PMFF) is a well-established technique utilized for reconstruction of complex nasal defects. Objective: To identify the different techniques and management of patients undergoing PMFF reconstruction and compare these with current literature. Methods: Members of the American Academy of Facial Plastic and Reconstructive Surgery were sent a practice survey highlighting various nuances in PMFF reconstruction. The survey included questions about flap design, operative techniques, and perioperative care. Results: In total, 172 responses were received (14% response rate). Mean years of practice after fellowship was 15.8 years with most respondents performing either 1-5 (33.1%) or 6-10 (27.3%) PMFFs per year. Common practices included the use of general anesthesia, elevation of PMFF in the subgaleal plane (59.6%), and pedicle division at 3 weeks (80%) (p < 0.001). Complication rates ranged between 1% and 5%. The nose was the most common site for revision (p < 0.001) and the average number of secondary procedures after forehead flap division was 1.1 (standard deviation 0.81). The most variability in responses was seen for methods of internal lining reconstruction. Conclusion: Reconstructive surgeons frequently divide the PMFF pedicle at 3 weeks or later and have variable approaches to reconstruction of the internal lining with low complication rates overall.

Normative Values of the Nasal Obstruction Symptom Evaluation Scale.

Background: The Nasal Obstruction Symptom Evaluation (NOSE) scale is widely used by clinicians in evaluation of nasal airway obstruction (NAO). Objective: To determine normative values for the NOSE scale among both symptomatic and asymptomatic members of the general U.S. population. Methods: A survey of NAO symptoms in adults of age 18 years and older was performed. The distribution of NOSE scores among the general population was estimated. Influence of features including age, gender, race, location, and symptomatology on NOSE scores was evaluated. Results: Surveys were completed by 2333 participants. Mean NOSE score was 11 (standard deviation [SD] 11) in the asymptomatic, and 28 (SD 22) in the symptomatic population (p < 0.0001). Increasing age was associated with an increase in scores until 45 years, after which it was associated with decreasing scores. No significant differences were found related to other investigated demographics. Conclusions: Normative ranges for the NOSE scale are established, and are largely consistent with values in the existing literature. NOSE scores do not appear to be influenced by gender, race, or geography, although age should be considered in their interpretation.

Prevalence and Characteristics Associated with Positive Body Dysmorphic Disorder Screening Among Patients Presenting for Cosmetic Facial Plastic Surgery.

Background: Many patients with body dysmorphic disorder (BDD) seek out cosmetic surgery to alleviate their symptoms of distress related to a perceived defect in their appearance; however, the prevalence and risk factors for BDD among patients with cosmetic concerns have not been well characterized. Methods: We screened adult patients presenting to the clinic from June 2021 through September 2022 for BDD using the BDD Questionnaire-Aesthetic Surgery (BDDQ-AS) who were seen in consultation for rhinoplasty, aging face, and injectables. Results: Among 488 patients, the prevalence of screening positive for BDD was 41.0%. The prevalence of a positive BDD screen was highest among patients who were younger (p = 0.02), and those who had a positive self-reported psychiatric history (p = 0.02). Among rhinoplasty patients, those with aesthetic/cosmetic motivations, and those seeking revision rhinoplasty had higher rates of positive BDD screen. Higher scores on the Standardized Cosmesis and Health Nasal Outcomes Survey-Nasal Obstruction Score (SCHNOS-O) (p = 0.01) and Standardized Cosmesis and Health Nasal Outcomes Survey-Nasal Obstruction Score-Nasal Cosmesis Score (SCHNOS-C) (p < 0.0001) were predictive of a positive BDD screen, while question 5 of the SCHNOS was highly predictive of positive BDD screening (p < 0.0001). Conclusions: Our study characterizes relationships between positive BDD screening and age, gender, self-reported psychiatric history, and motivations for consultation, among patients seen for cosmetic surgery evaluation in a facial plastic and reconstructive surgery setting.

Chemodenervation of the Posterior Belly of the Digastric Muscle in Facial Synkinesis.

Background: Patients with facial synkinesis may have jaw tightness and swallow discomfort despite chemodenervation of facial mimetic musculature, and the posterior belly of the digastric (PBD) muscle is a logical target to treat these symptoms. Learning/Study Objective: To compare patient-reported outcomes of botulinum toxin (BT) chemodenervation of the posterior belly of digastric muscle in patients with postparalytic facial synkinesis. Design Type: Retrospective review. Methods: Patients with facial synkinesis who underwent electromyography (EMG)-guided PBD BT chemodenervation in addition to their baseline therapeutic regimen were included. Pre- and post-treatment Synkinesis Assessment Questionnaires (SAQ) and a two-question survey regarding jaw tightness and swallow discomfort were administered. Results: Twenty-nine patients were included. An average of 5 U of BT-A was injected into the PBD, and 46.5 U across all facial muscles. From pre- to post-injection, patients demonstrated improvement in jaw tightness at rest (3.02 vs. 1.98/5.0, p < 0.001), with swallow (2.78 vs. 1.94/5.0, p < 0.001), and total SAQ (64.3 vs. 51.2/100, p < 0.001). Patients rated subjective benefit from PBD injection compared with prior treatments without PBD injection as 4.5/5.0. Conclusion: Synkinesis patients with jaw tightness or swallow discomfort may benefit from the addition of PBD injections to the therapeutic regimen.

Upper respiratory tract microbiota dynamics following COVID-19 in adults.

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 ⍺-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; 95 % 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 (71.43 %) 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.

Complications Associated with Use of Porous High-Density Polyethylene in Rhinoplasty.

Background: Porous high-density polyethylene (pHDPE) has successfully been used as an alternative to cartilage for grafting in rhinoplasty; however, concerns exist surrounding its potential for infection and/or extrusion. Objectives: To analyze the relationship between complication rates associated with pHDPE in rhinoplasty and graft location relative to shear force applied by external manipulation. Methods: Retrospective review of 116 patients undergoing pHDPE rhinoplasty for 10 years. Results: Minor postoperative complications occurred in 3.4% of patients, each resolving with conservative management. Major complications including infection or extrusion occurred in 5.2% of all patients, at an average of 36.9 months postoperatively. All major complications occurred in patients with grafts extending into the caudal nose, and two-thirds ultimately necessitated surgical intervention. Conclusions: Cephalically contained pHDPE grafts are less prone to failure than those extending into the caudal nose. Long-term follow-up is recommended for all patients based on the risk for delayed complications.

Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load.

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.

Pharmacokinetic-based failure of a detergent virucidal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nasal infections: A preclinical study and randomized controlled trial.

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.

Septal Perfoplasty for Management of Symptomatic Nasal Septal Perforation: An Alternative to Surgical Closure.

Importance: Symptomatic septal perforations are often difficult to manage and can have a significant impact on patient quality of life. Available surgical techniques for repair have demonstrated a varying rate of success, presenting a need for reliable interventions targeting symptom control. Objectives: To describe the modified surgical technique here termed septal perfoplasty. To demonstrate that creation of favorable septal perforation characteristics is effective in managing symptoms and improving patient quality of life. Design, Setting, and Participants: A retrospective review of the medical record was performed of patients who underwent the procedure of interest between July 1, 2006 and October 1, 2019 at Vanderbilt University Medical Center. All patients with symptomatic septal perforation who underwent septal perfoplasty within the timeframe reviewed were included. Septal perfoplasty was standardly performed in combination with turbinate reduction in all cases. This was combined with other indicated procedures for chronic sinusitis, repair of vestibular stenosis or nasal deformity. Main Outcomes and Measures: Creation of a well-mucosalized septal perforation, combined with patient-reported acceptable symptom control, was the primary outcome. Secondary outcomes include time to resolution, duration of follow-up, postsurgical complications, and need for further intervention. Results: Twenty patients (70% female; mean [range] age, 45.8 [15-72] years) underwent septal perfoplasty over the course of 13 years. The most common etiology of perforation was trauma (40%), presenting symptom was crusting (95%), and size of perforation repaired was large (60%). Mean follow-up was 37.6 months (range, 1-153 months). Overall, favorable perforation characteristics were created in 95% of cases by the first postoperative appointment. Acceptable symptomatic control was achieved in 18 out of 20 patients (90%), with a median time to improvement of 66 days. Eight patients required additional surgery to address chronic sinusitis or vestibular stenosis. Two patients experienced postoperative infections, treated conservatively with antibiotics. Conclusion and Relevance: Septal perfoplasty is a safe, simple, and effective method for management of symptomatic nasal septal perforation, which provides an alternative to more complicated interventions with comparable rates of symptomatic resolution. This procedure should particularly be considered for patients in which difficult repair is anticipated.

Severe COVID-19 Is Associated With an Altered Upper Respiratory Tract Microbiome.

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.

Pharmacokinetic-based failure of a detergent virucidal for SARS-COV-2 nasal infections.

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.

Outcomes of Revision Cochlear Implantation.

OBJECTIVES/HYPOTHESIS: This study aims to 1) report revision cochlear implantation (CI) rates at a high-volume CI center, 2) describe classifications for revision CI, 3) analyze audiologic and surgical outcomes in patients who undergo revision CI, and 4) describe a new subcategory of soft failures, named presumed soft failures. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care otologic center. PATIENTS: Adults and children undergoing revision CI from 2005 to 2015. MAIN OUTCOME MEASURE: Type and etiology of CI failure, preoperative, and postoperative outcomes (audiologic, surgical). RESULTS: During the study period, 1,469 CI surgeries were performed with a total of 81 (5.51%) revision cochlear implantations, 64 of these meeting inclusion criteria with adequate follow up and clear indications for revision surgery. The most common indication for revision surgery was hard failure (53.1%), followed by soft failure (29.7%), and medical/surgical failure (17.2%). 78.1% (50/64) of revision CI patients showed improvement postoperatively (defined as 15% improvement of speech perceptions scores or improvement of aversive symptoms, according to the 2005 consensus statement guidelines). Hard failures showed improvement in 85.3% (29/34) of cases, medical and surgical failures showed improvement in 72.7% (8/11) of cases, and soft failures showed improvement in 68.4% (13/19) of cases. There was a statistically significant difference in percentage of adult versus pediatric patients by failure subtype, with 84.2% of soft failure patients classified as adults (18 or older) at the time of revision surgery compared with 50% and 36.3% for hard failure and medical/surgical failure patients, respectively (p = 0.02). Similarly, there was a trend, though not statistically significant, towards older age in the soft failure group compared with hard and medical/surgical failure groups (median 43 yr versus 18 and 16, respectively). Within the soft failure group there was a subset of patients that failed to show improvement in audiologic performance or experienced continued aversive symptoms referred to as "presumed soft failures." These patients, by definition, experienced worse outcomes after revision surgery (p < 0.05) and trended towards older age (43 versus 31 yr) and longer time from initial to revision surgery (27.3 versus 24.7 mo) when compared with true soft failures. CONCLUSIONS: The majority of patients improved after revision CI surgery; patients with hard failure demonstrated the highest percentage with improvement, while those with soft failures had worse outcomes. The presumed soft failure group may represent a unique etiology for CI failure that warrants further investigation given worse outcomes after revision surgery.