Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

INTRODUCTION: While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. METHODS: COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. RESULTS: Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. CONCLUSION: IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

Bilateral Inferior Turbinate Flaps for Salvage Reconstruction after Proton Beam Radiotherapy for Clival Chordoma.

Clival chordoma is a rare, aggressive, notochord-derived tumor primarily managed with surgery via an endoscopic endonasal approach (EEA) and adjuvant proton beam radiotherapy. Reconstruction is commonly performed with a nasoseptal flap (NSF) at the time of initial surgery. While failures of the NSF are rare, they can occur following the initial surgery or in the setting of osteoradionecrosis. Salvage repair typically requires transfer of alternative vascularized tissues outside of the previously radiated field including regional scalp flaps such as pericranial or temporoparietal fascial flaps, or free vascularized tissue transfer. Here we describe the case of a 29-year-old woman with a history of clival chordoma with widespread skull base osteomyelitis secondary to NSF necrosis after proton beam radiotherapy. We describe successful skull base reconstruction with intranasal bilateral inferior turbinate flaps based on the sphenopalatine artery with lateral nasal wall extension, despite prior proton beam therapy and a failed prior vascularized intranasal reconstruction.

Impact of COVID-19 versus chronic rhinosinusitis/rhinitis associated olfactory dysfunction on health utility and quality of life.

Background: Olfactory dysfunction (OD) is associated with both post-viral and inflammatory etiologies such as COVID-19 and chronic rhinosinusitis/rhinitis (CRS/R) respectively, to result in reduced quality of life (QoL). However, the former typically induces a sudden-onset OD while the latter has a gradual presentation. This study aims to establish and compare health utility values (HUVs) and olfactory-specific QoL measurements between patients with COVID-19 and CRS/R related OD. Methods: This prospective study surveyed COVID-19 and CRS/R patients with self-reported OD using HUV assessments (EuroQol-visual analog scale [EQ-VAS], EuroQol-5 dimension [EQ-5D], time trade-off [TTO]) and olfactory and sinonasal QoL measures (questionnaire of olfactory disorders -negative and positive statements [QOD-NS + PS] and sino-nasal outcome test [SNOT-22]). A subgroup of subjects completed objective olfactory testing. Intergroup mean scores were compared using Mann-Whitney U tests. Results: One hundred eleven subjects were enrolled: mean age ± SD (43.0 ± 15.4 years), 55.9% female. CRS/R was associated with lower HUVs as measured by EQ-VAS (CRS/R: 0.67 ± 0.18 vs. COVID-19: 0.74 ± 0.19, p = .03) and worse SNOT-22 scores in both overall (CRS/R: 49.03 ± 21.04 vs. COVID-19: 27.58 ± 18.45, p < .001) and subgroup analysis of objectively confirmed OD subjects (CRS/R: 52.40 ± 22.78 vs. COVID-19: 29.84 ± 21.10, p = .01). On the other hand, COVID-19 has greater burden on olfactory-specific QoL (QOD-NS + PS, COVID-19: 23.19 ± 13.73 vs. CRS/R: 17.25 ± 11.38, p = .04). Both groups demonstrated a similar decrease in health using the EQ-5D assessment. Conclusion: CRS/R associated OD has a more severe impact on general health and sinonasal specific QoL outcomes, while COVID-19 associated OD has a greater burden on olfactory-specific QoL. Level of evidence: Level 2c.

Modified Endoscopic Denker's Approach for Management of Anterior Maxillary Sinus Tumors: Multicenter Series of 58 Cases.

OBJECTIVES: Tumors involving the anterior portion of the maxillary sinus remain technically challenging to access via an endoscopic approach. The modified endoscopic Denker's (MED) procedure was recently introduced to address such lesions. We present a multicenter series of 58 patients with tumors involving the anterior maxillary sinus successfully resected using a MED procedure and present the clinical outcomes and complications. METHODS: A multi-institution retrospective chart review was performed on patients who underwent the MED approach for the management of tumors involving the anterior maxillary sinus from 2009 to 2020. Demographic data, pathology, surgical outcomes, and complications were reviewed. RESULTS: Fifty-eight patients were identified, including 34 (58.6%) male and 24 (41.4%) female patients. The most common pathologies included: inverted papilloma (n = 27; 46.6%), adenoid cystic carcinoma (n = 9; 15.5%), and squamous cell carcinoma (n = 8; 13.8%). Thirty-eight patients (65.5%) underwent MED alone, while 20 (34.5%) had combined expanded endonasal approaches for lesions extending beyond the maxillary sinus. All maxillary sinus lesions were successfully accessed with the MED procedure without the need for an additional approach. After a mean follow-up of 30 months (range, 1-127), 8 of 58 (13.8%) patients developed complications related to the MED, including epiphora requiring an additional procedure (n = 4; 6.9%), prolonged facial/palatal numbness (n = 3; 5.2%), severe epistaxis (n = 1; 1.7%), and vestibular stenosis (n = 1; 1.7%), the latter of which occurred following postoperative radiation. CONCLUSION: The MED procedure is a safe and highly effective approach for benign and malignant tumors involving the anterior maxillary sinus. However, patients should be counseled preoperatively on potential complications including the risk of facial numbness and epiphora.

Steroid-eluting Stent Placement for Refractory Stenosis of Parotid Megaduct After Sialodochoplasty.

Salivary megaduct with stricture is characterized by recurrent pain, swelling, and infection, leading to reduced quality of life. Surgical management includes sialodochoplasty, however, recurrence is common and repeated surgery can lead to further scarring. In the sinuses, drug-eluting stents (DES) are used to reduce scarring after surgery, yet no such technology exists for salivary megaduct with stricture.We trialed DES for this condition with promising results which may pave the way for future development.

Clinical factors associated with lower health scores in COVID-19-related persistent olfactory dysfunction.

BACKGROUND: Patients with persistent COVID-19 olfactory dysfunction (OD) commonly report parosmia. Understanding the impact of COVID-19 OD and parosmia is critical to prioritizing research and interventions. In this study we investigate the impact of parosmia and other clinical and disease characteristics on health state utility values (HUVs) for those with persistent COVID-19 OD. METHODS: Patients with a history of COVID-19 diagnosis and persistent OD were recruited from a tertiary medical center and a social media support forum for chemosensory dysfunction. Clinical characteristics and disease-specific symptoms were obtained along with self-reported history of smell function and presence of parosmia. HUVs were calculated using indirect (EuroQol 5-Dimension [EQ-5D]) and direct (VAS) measures. RESULTS: Our study included 286 subjects (75.52% women) with persistent COVID-19-related OD. Results (mean ± standard deviation) of HUVs based on EQ-5D and VAS were 0.81 ± 0.14 and 0.73 ± 0.21, respectively. Mean self-reported smell function (on a 0-10 scale) was 9.67 ± 1.25 pre-COVID-19, 0.93 ± 2.34 at diagnosis, and 3.39 ± 2.32 at most current assessment. A total of 89.16% of the subjects reported parosmia and 24.13% sought medical care for anosmia. Seeing an MD for OD (p < 0.001), female gender (EQ-5D only, p = 0.002), a history of chronic pain (p < 0.05) and depression/anxiety (EQ-5D only, p < 0.001) predicted worse health. Parosmia and persistent symptoms, such as shortness of breath, were associated with lower EQ-5D and VAS scores, but did not independently predict poorer health scores on multivariable analysis. CONCLUSION: Persistent COVID-19 OD results in health states comparable to other chronic diseases.

Immunohistochemical and qPCR Detection of SARS-CoV-2 in the Human Middle Ear Versus the Nasal Cavity: Case Series.

Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-ß1 levels between smokers and non-smokers.

Assessment of patient recognition of coronavirus disease 2019 (COVID-19)-associated olfactory loss and recovery: a longitudinal study.

BACKGROUND: The clinical course of coronavirus disease 2019 (COVID-19) olfactory dysfunction remains poorly characterized, often limited by self-reported measures. Given the logistical challenges of psychophysical testing, understanding the longitudinal relationship between self-reported and quantitative measures can help accurately identify patients with persistent olfactory dysfunction. This study aimed to longitudinally correlate measured and subjective olfactory function in COVID-19 subjects. METHODS: A prospective, longitudinal study evaluating subjective and measured olfaction was conducted on ambulatory COVID-19 subjects. Olfaction scores were obtained using a visual analogue scale (VAS) (0 = anosmia, 10 = normosmia) and the validated 12-item Brief Smell Identification Test (BSIT). Weekly testing was performed until recovery (BSIT ≥ 9/12 and/or VAS = 10/10) or study completion. RESULTS: Eighty-six polymerase chain reaction (PCR)-positive COVID-19 subjects were recruited ≤3 days from diagnosis and 52 completed longitudinal testing. Among those with self-reported smell loss at recruitment, similar levels (75.8%) of objective (BSIT ≥ 9/12) and subjective recovery were obtained using a VAS cutoff ≥8, yet only 30.3% reported complete subjective recovery (VAS = 10). Median times to objective and complete subjective olfactory recovery were 12 ± 2.3 and 24 ± 3.5 days, respectively. Although both measures showed chemosensory improvement, the distributions of objective and full subjective olfactory recovery differed significantly (log rank test χ2 = 6.46, degrees of freedom [df] = 1, p = 0.011). Overall correlation between BSIT and VAS scores was moderate to strong across longitudinal follow-up (rs = 0.41-0.65). CONCLUSION: Self-reported and psychophysically measured COVID-19 olfactory dysfunction improve at similar levels and are moderately correlated longitudinally, yet there is a significant delay in complete subjective recovery. Psychophysical testing in conjunction with qualitative assessments may be considered for counseling and follow-up of patients with COVID-19 smell loss.

A case of mistaken identity: Saksenaea vasiformis of the orbit.

The authors describe a rare presentation of invasive fungal rhino-orbital cellulitis caused by Saksenaea vasiformis in an immunocompetent child. The patient was initially diagnosed and treated as Mucoraceae, which has a high mortality rate and is primarily seen in immunocompromised patients. Though of the same order, Mucorales, the families Mucoraceae and Saksenaeacae, may be difficult to differentiate on histologic examination and must be distinguished by fungal culture and speciation. Our patient responded well to sino-orbital debridement and systemic treatment with amphotericin and posaconazole.

Rate and Factors Associated With Change in Surgeon for Revision Endoscopic Sinus Surgery.

OBJECTIVES/HYPOTHESIS: A subset of patients will undergo revision endoscopic sinus surgery (ESS) with a different otolaryngologist than the one who performed their primary surgery. The purpose of this study is to report the incidence of and clinicodemographic factors associated with a change in surgeon for revision ESS. STUDY DESIGN: Retrospective cohort study. METHODS: Adult patients who underwent at least two outpatient ESS procedures between 2009 and 2014 using the State Ambulatory Surgery Database for Florida were included in the study. Change in surgeon was defined by a change in a unique provider identifier for the revision procedure. Multivariable regression analysis was used to determine characteristics associated with a change in surgeon. RESULTS: A total of 2,963 patients were included. For the revision procedure, 47.7% of patients changed their surgeon. On multivariable logistic regression, a medium- (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.53-0.77) or high-volume (OR: 0.50; 95% CI: 0.42-0.61) surgeon performing the index surgery and advanced age (≥65 years) (OR: 0.79; 95% CI: 0.63-0.99) were associated with decreased odds of surgeon change for revision ESS. Longer time elapsed between index and revision surgery (OR: 1.15; 95% CI: 1.13-1.17) was associated with increased odds of surgeon change. CONCLUSIONS: Nearly half of patients who undergo revision ESS select a surgeon other than the one who performed their primary procedure. Surgeon volume, age, and time between surgeries affect the likelihood of a change in surgeon for revision ESS. These findings may provide introductory insights into patient preferences and decision making in the surgical management of recalcitrant chronic rhinosinusitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1049-E1053, 2021.

Association of subjective olfactory dysfunction and 12-item odor identification testing in ambulatory COVID-19 patients.

BACKGROUND: Acute loss of smell and taste are well-recognized symptoms of coronavirus disease 2019 (COVID-19), yet the correlation between self-reported and psychophysical olfactory function remains unclear. Understanding the reliability of self-reported smell loss in ambulatory cases can assess the utility of this screening measure. METHODS: A prospective, longitudinal study evaluating patient-reported and measured olfactory function using the validated 12-item Brief Smell Identification Test (BSIT) was conducted on adult outpatients with COVID-19. Patient-reported olfaction scores using a visual analog scale (VAS) were obtained at baseline, time of COVID-19 testing, and time of BSIT completion. Linear associations between VAS and BSIT were evaluated using Spearman's correlation coefficient and the sensitivity, specificity, and accuracy of VAS scores were calculated. Logistic regression identified characteristics associated with accurate assessment of olfactory function. RESULTS: A total of 81 polymerase chain reaction (PCR)-confirmed COVID-19 positive subjects, of whom 54 self-reported smell loss, were prospectively recruited ≤5 days from diagnosis date between May 8, 2020, and July 8, 2020. Self-reported smell loss had good discriminative ability in identifying abnormal BSIT (area under receiver operating curve [AUC] 0.82, 95% confidence interval [CI], 0.71 to 0.92). A VAS <5 demonstrated sensitivity of 0.62 and specificity of 0.94 for predicting hyposmia (BSIT ≤8) with accuracy of 82.7%, whereas a VAS <9 had highest sensitivity at 0.86. Moderate bivariate linear associations were found between VAS and BSIT scores (rs = 0.59, p < 0.001). CONCLUSION: Self-reported olfactory loss associated with COVID-19 has a strong ability to predict abnormal olfactory function though the 2 measures are moderately correlated. Subjective olfactory assessment is useful in screening olfactory dysfunction at early disease time points when psychophysical testing cannot be conducted.

Elective neck dissection for T3/T4 cN0 sinonasal squamous cell carcinoma.

BACKGROUND: In locally advanced sinonasal squamous cell carcinoma (SNSCC), management of the clinically node-negative (cN0) neck is variable and elective neck dissection (END) remains controversial. METHODS: Patients with surgically treated T3/T4 cN0 M0 SNSCC were identified using the NCDB. Overall survival (OS) was assessed by Cox proportional hazard analysis in propensity score-matched cohorts. Factors associated with END were evaluated with logistic regression. RESULTS: Two hundred twenty patients underwent END (19.6%). END did not correlated with OS in propensity score-matched cohorts (HR 0.971, 95% CI 0.677-1.392), a maxillary sinus tumor subgroup (HR 1.089, 95% CI 0.742-1.599), or by radiation status [radiation: (HR 0.802, 95% CI 0.584-1.102); no radiation: (HR 0.852, 95% CI 0.502-1.445)]. The occult metastasis rate in the END cohort was 12.7%. CONCLUSION: END did not significantly improve OS in this study. Further information on disease-free survival is necessary to determine its role in advanced-stage SNSCC.

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma.

BACKGROUND: Although treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma. METHODS: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan-Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models. RESULTS: The analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity-score matched cohort (n = 195; hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75). CONCLUSION: Compared to current standard of care therapy, inclusion of immunotherapy as first-line therapy was not associated with improved survival in SNM.

Predicting COVID-19 Incidence Using Anosmia and Other COVID-19 Symptomatology: Preliminary Analysis Using Google and Twitter.

OBJECTIVE: To determine the relative correlations of Twitter and Google Search user trends concerning smell loss with daily coronavirus disease 2019 (COVID-19) incidence in the United States, compared to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. To describe the effect of mass media communications on Twitter and Google Search user trends. STUDY DESIGN: Retrospective observational study. SETTING: United States. SUBJECTS AND METHODS: Google Search and "tweet" frequency concerning COVID-19, smell, and nonsmell symptoms of COVID-19 generated between January 1 and April 8, 2020, were collected using Google Trends and Crimson Hexagon, respectively. Spearman coefficients linking each of these user trends to COVID-19 incidence were compared. Correlations obtained after excluding a short timeframe (March 22 to March 24) corresponding to the publication of a widely read lay media publication reporting anosmia as a symptom of infection was performed for comparative analysis. RESULTS: Google searches and tweets concerning all nonsmell symptoms (0.744 and 0.761, respectively) and COVID-19 (0.899 and 0.848) are more strongly correlated with disease incidence than smell loss (0.564 and 0.539). Twitter users tweeting about smell loss during the study period were more likely to be female (52%) than users tweeting about COVID-19 more generally (47%). Tweet and Google Search frequency pertaining to smell loss increased significantly (>2.5 standard deviations) following a widely read media publication linking smell loss and SARS-CoV-2 infection. CONCLUSIONS: Google Search and tweet frequency regarding fever and shortness of breath are more robust indicators of COVID-19 incidence than anosmia. Mass media communications represent important confounders that should be considered in future analyses.

Persistent Smell Loss Following Undetectable SARS-CoV-2.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

Incidence and Predictive Factors for Additional Opioid Prescription after Endoscopic Skull Base Surgery.

Introduction Postoperative pain management and opioid use following endoscopic skull base surgery (ESBS) is not well understood. A subset of patients requires additional opioid prescription (AOP) in the postoperative period. The objective of this study is to describe the incidence of AOP, as well as evaluate patient and surgical characteristics that may predict additional pain management requirements following ESBS. Methods A retrospective review of cases undergoing ESBS between November 2016 and August 2018 was performed. We reviewed patients' sociodemographic and clinical data, and Controlled Substance Utilization Review and Evaluation System (CURES) records. Stepwise multivariable logistic regressions were performed to evaluate the factors associated with AOP within 60 days following surgery. Results A total of 42 patients were identified. Indications for ESBS included intracranial mass (64.2%), sinonasal malignancy (23.8%), and skull base reconstruction (9.5%). AOP were recorded in nine patients (21.4%). There were no significant differences in operative factors, including approach, lesion location, or perioperative analgesia between the two cohorts. On multivariable logistic regression, we found that younger age (odds ratio [OR]: 0.891, 95% confidence interval [CI]: 0.79-1.00, p = 0.050), comorbid depression (OR: 86.48, 95% CI: 1.40-5,379.07, p = 0.034), and preoperative opioid use (OR: 104.45, 95% CI: 1.41-7,751.10, p = 0.034) were associated with additional prescriptions postoperatively. Conclusion The requirement for extended postoperative opioid pain control is common after ESBS. Patient demographics including age and psychosocial factors, such as depression may predict the need for AOP after ESBS. These results suggest that patient-driven factors, rather than surgical characteristics, may determine the need for prolonged pain control requirements after ESBS.