Immunological memory diversity in the human upper airway.

The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory B cells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than 1 year, and prominent tissue resident memory T (TRM) cell and B (BRM) cell populations were defined. Unexpectedly, germinal centre cells were identified consistently in many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRM cells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ TRM cells and CD8+ TRM cells were identified, with diverse additional virus-specific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.

Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. OBJECTIVE: We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. METHODS: Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. RESULTS: Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). CONCLUSION: Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

Pediatric Nasal Chondromesenchymal Tumors: Case Report and Review of the Literature.

INTRODUCTION: Nasal chondromesenchymal tumors (NCMT) are rare benign neoplasms that usually present in children <1 year of age. They can display rapid growth and significant local bony remodeling that can mimic a malignant process. Of the ∼50 published cases to date, few have documented the need for neurosurgical intervention. We herein report a NCMT in an infant treated with a staged cranial and transnasal approach, as well as summarize the available literature on this pathology. CASE REPORT: A newborn male with a compromised airway was noted to have a large sinonasal lesion. After stabilization, MRI demonstrated a 4-cm enhancing mass with diffuse sinus involvement and significant extension into the anterior cranial fossa, with displacement of the optic apparatus and hypothalamic pituitary axis. After an initial biopsy, the patient underwent a bifrontal craniofacial approach at 2 months of age, followed by a second-stage transnasal endoscopic approach at 15 months which resulted in a complete resection. There were no neurosurgical complications. Pathology was consistent with a NCMT. DISCUSSION: Although rare, neurosurgical involvement is critical for the treatment of NCMTs with intracranial extension. Staged cranial and endonasal endoscopic approaches may be needed for complete resection of such lesions.

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.

A systematic review of the nasal septal turbinate: An overlooked surgical target.

OBJECTIVE: The nasal septal turbinate (NST) is a conspicuous structure located in the anterior nasal cavity that impacts the internal nasal valve. Its structure and function is often thought to be poorly characterized, and it is rarely addressed surgically. The authors perform a systematic review in an attempt to synthesize what has been learned of this structure and to evaluate its potential as a treatment target. METHODS: A query of the Medline, Embase, Web of Science and Cochrane databases was undertaken in search of studies evaluating the NST. This qualitative systematic review was performed in accordance with PRISMA guidelines. Study quality and risk of bias were assessed with established criteria. RESULTS: Of the initial 1069 hits from the four databases, 16 articles were ultimately included in the review, which varied in quality and risk of bias. The included articles consisted predominantly of radiographic and histopathologic studies. Four studies evaluated NST treatment outcomes. The NST represents a fusiform-shaped region of erectile tissue, similar in structure and function to that of the inferior turbinates. Preliminary treatment outcomes suggest the NST represents an important surgical target in nasal airway surgery. CONCLUSION: When evaluating nasal obstruction patients, surgeons should assess the NST and consider addressing it surgically.

Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD. OBJECTIVE: We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD. METHODS: Blood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2 metabolite and leukotriene E4 levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes. RESULTS: ILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2 metabolite and leukotriene E4 levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity. CONCLUSIONS: ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.

Can sinus anatomy predict quality of life outcomes and operative times of endoscopic frontal sinus surgery?

PURPOSE: Endoscopic sinus surgery (ESS) can manipulate sinus anatomy, but with limitations due to skull base and orbit anatomy. These anatomical structures dictate the maximal extent of ESS in the frontal recess and may limit surgical extent or operative duration. This study investigates the impact of these anatomical constraints on operative time and quality-of-life (QOL) outcomes. MATERIALS AND METHODS: Patients with medically refractory chronic rhinosinusitis undergoing Draf IIa frontal sinus surgery were prospectively enrolled. Anatomic measurements of the frontal sinus anatomy were collected during computed tomography review and included: widest distance between the frontal beak and posterior table, narrowest point in the ethmoid bed, Keros height, presence of an anterior ethmoid artery on a mesentery, and presence of inter-sinus septal cells. Primary outcomes included mean operative time and improvement in SinoNasal Outcome Test (SNOT-22) survey scores. RESULTS: 63 adult participants were enrolled and followed 13.8 (5.2) months on average. The ethmoid bed mean width was 7.2 (1.4) mm, the mean distance from frontal beak to the posterior table at widest was 9.0 (2.7) mm, and mean Keros height was 5.1 (1.8) mm. 49/63 (83.1%) of participants had inter-sinus septal cells and 30/63(50.8%) had anterior ethmoid arteries on a mesentery. Mean operative time was 121.5 (44.0) min while SNOT-22 scores significantly (p<0.001) improved 26.1 (21.6) on average. Anatomic measurements were not predictive of operative time or mean QOL change (p>0.050). CONCLUSIONS: Frontal sinus surgery is an effective treatment for a range of frontal and ethmoid sinus anatomy. Further study with larger sample size and measures of more restricted anatomy might elucidate treatment limitations of ESS.

Spontaneous ventilation of the frontal sinus after fractures involving the frontal recess.

PURPOSE: Frontal sinus fractures (FSF) have potentially catastrophic consequences due to frontal recess (FR) obstruction and proximity to the brain and orbit. Lack of follow-up and ability to predict which type of fractures predispose to complications has biased surgeons toward definitive interventions such as sinus obliteration and cranialization. These procedures carry inherent risk and may be unnecessary in a subset of patients. This study seeks to better characterize spontaneous ventilation in subjects with FSFs, including those involving the FR. MATERIALS AND METHODS: Review of a prospectively maintained trauma database between 2009 and 2013 at a level 1 trauma center. Patients with frontal sinus fractures with follow-up imaging (>6 weeks) available were included. The medical records and imaging were reviewed for evidence of spontaneous ventilation of the frontal sinus. RESULTS: Nineteen patients sustained frontal sinus fractures in the study period with mean imaging interval of 67.4 weeks (range, 6-188.4 weeks). Injury mechanisms included fall (32%), assault (31%), motor vehicle accident (17%), pedestrian-versus-automobile (12%), and gunshot wound (8%). 8/19 patients (42%) sustained FSFs involving the FR and 7/8 (87.5%) spontaneously ventilated by time of interval imaging. The one patient with persistent radiographic sinus opacification was associated with a naso orbital ethmoid and medial orbital blowout fracture. 6/19 patients (32%) sustained FSF sparing the FR, and all spontaneously ventilated by the time of interval imaging. 5/19 patients (26%) underwent surgical intervention. CONCLUSIONS: An expectant, sinus-preserving approach to acute FSFs involving the FR is safe and effective. Etiology of re-ventilation failure may be due to tissue obstruction, rather than the frontal recess fracture itself.

Biomimetic scaffolds facilitate healing of critical-sized segmental mandibular defects.

OBJECTIVE: To investigate the efficacy of biomimetic PLGA scaffolds, alone and in combination with bone morphogenic protein (BMP-2) and adipose-derived stem cells (ASCs), to heal a critical-sized segmental mandibular defect in a rat model. STUDY DESIGN: Prospective animal study. METHODS: ASCs were isolated and cultured from the inguinal fat of Lewis rat pups. Using three-dimensional printing, PLGA scaffolds were fabricated and impregnated with BMP-2 and/or ASCs. Critical-sized 5-mm segmental mandibular defects were created in adult Lewis rats and implanted with (1) blank PLGA scaffolds, (2) PLGA scaffolds with ASCs, (3) PLGA scaffolds with BMP, or (4) PLGA scaffolds with BMP and ASCs. Animals were sacrificed at 12weeks. Bone regeneration was assessed using microCT, and graded on a semi-quantitative bone formation and bone union scale. RESULTS: Twenty-eight rats underwent creation of segmental mandibular defects with implantation of scaffolds. Nine rats suffered complications and were excluded from analysis, leaving 19 animals for inclusion in the study. MicroCT analysis demonstrated no bridging of the segmental bony defect in rats implanted with blank scaffolds (median bone union score=0). Rats implanted with scaffolds containing BMP-2 (median bone union=2.0), ASCs (median bone union=1.5), and combination of BMP and ASCs (median bone union=1.0) demonstrated healing of critical-sized segmental mandibular defects. Bone regeneration was most robust in the BMP-2 treated scaffolds. CONCLUSIONS: The current study utilizes a novel animal model to study the efficacy of biomimetic scaffolds carrying osteogenic factors to induce healing of a critical-sized segmental mandibular defect. LEVEL OF EVIDENCE: N/A, Basic Science Animal Research.

Oncologic validity of recipient vessel preservation in microvascular free-flap reconstruction.

OBJECTIVES: The use of free-flap reconstruction requires a more limited neck dissection to allow for microvascular anastomosis. This study seeks to determine the oncologic validity of cervical vessel preservation. MATERIALS AND METHODS: The current study is a prospective review of cervical vessel biopsies from patients undergoing resection of squamous cell carcinoma (SCCA) tumors of the head and neck with free tissue reconstruction. RESULTS: From June 2010 to March 2012, 227 recipient vessel biopsies were performed on 100 patients. Three of these patients had grossly abnormal vessels, with malignancy confirmed by frozen section analysis. One patient had a vessel positive for malignancy that was grossly normal but found to have SCCA on the final pathology. CONCLUSIONS: When the recipient vessel appears grossly suspicious, a frozen section biopsy and re-resection should be considered. Recipient vessel trimmings should routinely be sent for permanent pathology since in rare cases, they can be involved by tumor, affecting the margin status, prognosis, and indications for adjuvant therapy.

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.

Nasal floor free mucosal graft for skull base reconstruction and cerebrospinal fluid leak repair.

OBJECTIVES: Donor sites for free mucosal grafts for endoscopic endonasal reconstruction of the skull base have traditionally included the middle turbinate, the inferior turbinate, and the nasal septum. The aim of this study was to demonstrate a free mucoperiosteal graft from the nasal cavity floor as a simple alternative donor site for mucosal grafts. METHODS: In a cadaver study with clinical correlation, we performed endoscopic endonasal harvest of the nasal floor free mucosal graft on two sides of a cadaveric nasal cavity. We also describe the cases of two patients in whom a nasal floor free mucosal graft was used to repair a skull base defect. RESULTS: The harvest of a nasal floor free mucosal graft is a quick, potentially less morbid method of obtaining free mucosal grafts. In the cases examined, use of this graft carried minimal morbidity and allowed for successful reconstruction of a skull base defect. CONCLUSIONS: Harvest of nasal floor mucosa is a technically simple method of obtaining free mucoperiosteum for reconstruction of the skull base.

Squamous cell carcinoma of buccal mucosa: a 40-year review.

PURPOSE: The aim of this study was to analyze the outcome of surgical therapy for buccal squamous cell carcinoma (SCCA) at a single tertiary care institution during a 40-year period. MATERIALS AND METHODS: A retrospective review was performed by examining the records and pathology of 48 patients with buccal SCCA treated at a single tertiary care institution from 1970 to 2009. RESULTS: Treatment entailed surgery alone in 18 patients (37.5%) and surgery followed by radiation therapy in 30 patients (62.5%). Composite resection was performed in 17 patients (35.4%), and ipsilateral neck dissections were performed in 37 patients (77.1%). One-year observed actuarial disease-free survival rates were 60%, 46%, 0%, and 40% for T1 through T4, respectively. Univariate analysis revealed increased age as a risk factor for disease recurrence (P = .062), with skin taken and neck dissection not achieving significance (P = .24 and .20, respectively). Multivariate analysis demonstrated age as increasing risk and neck dissection as decreasing risk of recurrence (P = .029 and .023, respectively). CONCLUSIONS: We report relatively high disease-free survival rates in patients who underwent aggressive resection and neck dissection. Performance of neck dissection and younger age were associated with a favorable prognosis. Performance of neck dissection may decrease the risk of recurrence in primary SCCA of the buccal mucosa. Although through-and-through resection of skin decreased risk of disease recurrence, this difference is not statistically significant (P = .24).

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.

Open and endoscopic surgery improve survival for squamous and nonsquamous cell nasopharyngeal carcinomas: An NCDB cohort study.

BACKGROUND: Nasopharyngeal tumors (NPTs) are primarily treated with nonsurgical therapy. Recent studies have demonstrated endoscopic salvage surgery for NPT recurrences may improve survival relative to reirradiation. However, there are very limited data on open compared with endoscopic approaches for NPTs. We investigated whether endoscopic and open surgical approaches to the nasopharynx improve overall survival for all histologic subtypes of NPTs. METHODS: We performed a retrospective cohort study using the National Cancer Database (NCDB). All adult patients with NPTs from 2004 to 2016 without distant metastasis who underwent treatment with curative intent were included. We extracted clinical and treatment variables to assess our primary outcome of overall survival. RESULTS: On univariate analysis, patients undergoing endoscopic surgery, but not open surgery, had significantly improved overall survival relative to those undergoing nonsurgical treatment. Post hoc analysis demonstrated significantly improved overall survival for surgery in patients with minor salivary gland histology, but not squamous cell carcinoma (SCC) histology or by T or N classification. A Cox proportional hazards model was used for multivariate regression. After adjusting for covariates, both endoscopic and open approaches were associated with improved overall survival relative to nonsurgical treatment for all tumor types. A multivariate regression of SCC found that open surgery, but not endoscopic surgery, was significantly associated with improved overall survival. CONCLUSION: Both endoscopic and open surgical approaches are associated with improved overall survival of patients with NPT. These findings highlight important oncologic validity as endoscopic and robotic platforms to the nasopharynx become more widely adopted.

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.

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.

Impact of Race, Ethnicity, and Socioeconomic Status on Nasopharyngeal Carcinoma Disease-Specific and Conditional Survival.

Introduction Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract-level composite score of SES to categorize patients. Kaplan-Meier analysis and Cox's regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results Our analysis included 5,632 patients. DSS was significantly associated with race and SES ( p < 0.01). Asian/Pacific Islander patients exhibited increased survival when controlling for other variables (hazard ratio [HR] = 0.73, p < 0.01). Although Black patients were more likely to be diagnosed with advanced disease (Black odds ratio [OR] = 1.47, p < 0.01), Black patients were also less likely to receive multimodal therapy; however, this relationship lost statistical significance once SES was incorporated into the multivariable analysis. DSS was decreased among the lowest (first) and middle (second) tertiles of SES (first HR = 1.34, p < 0.01; second HR = 1.20, p < 0.01) compared with the highest (third). Conclusion Our results indicate that race, ethnicity, and SES significantly affect survival, stage at diagnosis, and treatment of NPC. An interplay of tumor biology and inequalities in access to care likely drives these disparities.