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Social determinants of health (SDoH) are environmental conditions that influence health outcomes. As olfactory dysfunction (OD) in older individuals is associated with increased morbidity and mortality, we sought to investigate the impact of specific SDoH on olfactory function.A cross-sectional analysis of the Health, Aging and Body Composition Study, a US population-based epidemiologic cohort study, was performed. Olfactory function was assessed utilizing both a self-report and a psychophysical olfactory test (CC-SIT test). Multivariable logistic regressions were performed to examine associations between specific SDoH with self-reported anosmia (sOD) and objective anosmia (oOD) as assessed by psychophysical testing. Differences in sensitivity and specificity were evaluated with sample tests for equality of proportions.Of 2219 participants, 13% had oOD and 18% had objective hyposmia; only 10% had sOD. Individuals identifying as Black race had higher odds of oOD (odds ratio [OR]:1.41, 95% confidence interval [CI]:1.02-1.95), while females and those reporting family incomes ≥$50,000 had lower odds of oOD (OR: 0.46, CI:0.34-0.62; OR:0.52, CI:0.29-0.93), adjusting for covariates. No specific SDoH was significantly associated with sOD. The sensitivity and specificity of sOD for oOD was 23.1% and 92.0%, respectively. sOD had greater sensitivity in females than males (30.8% vs. 18.8%, p = 0.030), while specificity varied significantly depending on family income (range: 90.0%-94.8%, p = 0.033).Utilizing a large population-based study, we find disparities in the prevalence and self-recognition of OD among individuals of different gender, race, and income levels. Further effort is needed to evaluate factors propagating these disparities and to raise awareness of OD across all patient populations.

Background Nearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based review summarizes the evolving literature and offers recommendations for the clinician on the management of patients experiencing parosmia associated with COVID-19. Methods We performed a systematic search using independent queries in PubMed, Embase, Ovid, and Cochrane databases, then categorized articles according to themes that emerged regarding epidemiology, effect on quality of life, disease progression, prognosis, pathophysiology, diagnosis, and treatment of parosmia. Results We identified 123 unique references meeting eligibility and performed title and abstract review with 2 independent reviewers, with 74 articles undergoing full-text review. An inductive approach to thematic development provided 7 central themes regarding qualitative olfactory dysfunction following COVID-19. Conclusions While other respiratory viruses are known to cause qualitative olfactory disturbances, the incidence of parosmia following COVID-19 is notable, and correlates negatively with age. The presence of parosmia predicts persistent quantitative olfactory dysfunction. Onset can occur months after infection, and symptoms may persist for well over 7 months. Affected patients report increased anxiety and decreased quality of life. Structured olfactory training with essential oils is the preferred treatment, where parosmia predicts recovery of aspects of quantitative smell loss when undergoing training. There is limited evidence that nasal corticosteroids may accelerate recovery of olfactory function. Patients should be prepared for the possibility that symptoms may persist for years, and providers should guide them to resources for coping with their psychosocial burden.

OBJECTIVE Suprasellar meningioma resection via either the transcranial approach (TCA) or the endoscopic endonasal approach (EEA) is an area of controversy and active evaluation. Skull base surgeons increasingly consider patient-reported outcomes (PROs) when choosing an approach. No PRO measure currently exists to assess quality of life for suprasellar meningiomas. METHODS Adult patients undergoing suprasellar meningioma resection between 2013 and 2019 via EEA (n = 14) or TCA (n = 14) underwent semistructured interviews. Transcripts were coded using a grounded theory approach to identify themes as the basis for a PRO measure that includes all uniquely reported symptoms. To assess content validity, 32 patients and 15 surgeons used a Likert scale to rate the relevance of items on the resulting questionnaire and the general Patient-Reported Outcomes Measurement Information System–29 (PROMIS29). The mean scores were calculated for all items and compared for TCA versus EEA patient cohorts by using unpaired t-tests. Items on either questionnaire with mean scores ≥ 2.0 from patients were considered meaningful and were aggregated to form the novel Suprasellar Meningioma Patient-Reported Outcome Survey (SMPRO) instrument. RESULTS Qualitative analyses resulted in 55 candidate items. Relative to patients who underwent the EEA, those who underwent the TCA reported significantly worse future outlook before surgery (p = 0.01), tiredness from medications 2 weeks after surgery (p = 0.001), and word-finding and memory difficulties 3 months after surgery (p = 0.05 and < 0.001, respectively). The items that patients who received a TCA were most concerned about included medication-induced lethargy after surgery (2.9 ± 1.3), blurry vision before surgery (2.7 ± 1.5), and difficulty reading due to blurry vision before surgery (2.7 ± 2.7). Items that patients who received an EEA were most concerned about included blurry vision before surgery (3.5 ± 1.3), difficulty reading due to blurry vision before surgery (2.4 ± 1.3), and problems with smell postsurgery (2.9 ± 1.3). Although surgeons overall overestimated how concerned patients were about questionnaire items (p < 0.0005), the greatest discrepancies between patient and surgeon relevance scores were for blurry vision pre- and postoperatively (p < 0.001 and < 0.001, respectively) and problems with taste postoperatively (p < 0.001). Seventeen meningioma-specific items were considered meaningful, supplementing 8 significant PROMIS29 items to create the novel 25-item SMPRO. CONCLUSIONS The authors developed a disease- and approach-specific measure for suprasellar meningiomas to compare quality of life by operative approach. If demonstrated to be reliable and valid in future studies, this instrument may assist patients and providers in choosing a personalized surgical approach.

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Hypoxia drives malignant progression in part by promoting accumulation of the oncogenic transcription factor hypoxia inducible factor–1α (HIF-1α) in tumor cells. Tumor aggressiveness also relates to elevation of the cancer stem cell–associated membrane protein CD24, which has been causally implicated in tumor formation and metastasis in experimental models. Here, we link these two elements by showing that hypoxia induces CD24 expression through a functional hypoxia responsive element in the CD24 promoter. HIF-1α overexpression induced CD24 mRNA and protein under normoxic conditions, with this effect traced to a recruitment of endogenous HIF-1α to the CD24 promoter. Short hairpin RNA–mediated attenuation of HIF-1α or CD24 expression reduced cancer cell survival in vitro and in vivo at the levels of primary and metastatic tumor growth. CD24 overexpression in HIF-1α–depleted cancer cells rescued this decrease, whereas HIF-1α overexpression in CD24-depleted cells did not. Analysis of clinical tumor specimens revealed a correlation between HIF-1α and CD24 levels and an association of their coexpression to decreased patient survival. Our results establish a mechanistic linkage between 2 critically important molecules in cancer, identifying CD24 as a critical HIF-1α transcriptional target and biologic effector, strengthening the rationale to target CD24 for cancer therapy. Cancer Res; 72(21); 5600–12. ©2012 AACR.

PDF file - 25K, Detail of the gene signature of Ral-dependent transcription and molecular concepts

PDF file - 158K, Evaluation of CD24 and HIF1a expression in response to hypoxia and Deferoxamine in human bladder and prostate cancer cells

PDF file - 68K, Quantitation of visible lung for metastases after tail vein inoculation of UMUC-3 cell lines

PDF file - 88K, Western blot and ChIP for HIF-1beta in human bladder cancer cells

Supplementary Figures 1-5 from Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer

PDF file - 890K, Effects of CD24 and HIF1a depletion on in vitro and in vivo growth and metastasis of bladder and prostate cancer cells

Supplementary Methods, Table 1, Figure Legends 1-5 from Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer

PDF file - 45K, The CD24 promoter cloned from human prostate and bladder cells

Supplementary Figures S1-S4; Supplementary Table S1.

Many SARS-CoV-2 studies have supported the theory that the Type II alveolar epithelial cells (AEC-2) are the primary portal of entry of the virus into the lung following its brief nasal occupation. However, the theory of inhalational transmission of the virus from the ciliated and goblet nasal cells to the lung parenchyma is not supported by the imaging findings on chest computerized tomography (CT), leading the authors to consider an alternative pathway from the nose to the lung parenchyma that could explain the peripheral, basilar predominant pattern of early disease. Imaging supports that the pulmonary capillaries may be an important vehicle for transmission of the virus and/or associated inflammatory mediators to the lung epithelium.

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 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.

Background Anosmia/hyposmia affects 13.3 million people in the U.S. alone according to the recent U.S. National Health and Nutrition Examination Survey (NHANES). Hundreds of thousands more people with persistent olfactory dysfunction will be added to this number due to the COVID-19 pandemic. Patients with loss-of-function mutations in SCN9A, the gene encoding NaV1.7, experience anosmia in addition to congenital insensitivity to pain. Tsp1a is a recently discovered peptide that inhibits NaV1.7 with high potency and selectivity. In this study, we examined whether a fluorescently tagged version of Tsp1a could be used to visualize normal and damaged mouse olfactory nerves. Methods Athymic nude mice were intravenously injected with Tsp1a-IR800. As a control, mice were injected with PBS only, and as a blocking control were injected with combination of Tsp1a and Tsp1a-IR800. All mice were imaged in-vivo and epifluorescence images were acquired using an IVIS Spectrum animal imaging system. Semiquantitative analysis of the Tsp1a-IR800 signal was conducted by measuring the average radiant efficiency in the region of the olfactory epithelium/bulb (ROEB). Methimazole was used to chemically ablate the olfactory epithelium. We performed a food buried test to correlate the level of anosmia with the level of radiance efficiency. Results The area of olfactory epithelium/bulb was clearly visible in epifluorescence in-vivo images of mice receiving the imaging agent. The radiant efficiency was significantly less in both mice injected with PBS and in mice injected with the blocking formulation. The mice after olfactory ablation had a significantly reduced radiant efficiency compared with normal mice. Moreover, there was a statistically significant and inverse correlation between the time required for the mouse to find buried food and the radiant efficiency. We also performed immunohistochemistry using NaV1.7 antibody. Mice after olfactory ablation as well as COVID-19-infected mice had significantly lower expression of NaV1.7 on the level of olfactory epithelium/bulb. Conclusion We show that the fluorescent imaging of mouse olfactory epithelium/bulb is possible, suggesting that labeled Tsp1a tracers may serve as the first objective diagnostic tool of smell disorders, including those caused by COVID-19.

Socioeconomic status (SES) is often used to quantify social determinants of health. This study uses the National Cancer Institute SES index to examine the effect of SES on disease-specific survival and 5-year conditional disease-specific survival (CDSS; the change in life expectancy with increasing survivorship) in paranasal sinus cancer.Cross-sectional analysis.National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program.A study of adults with sinus cancer between 1973 and 2015 was performed. The Yost index, a census tract-level composite score of SES, was used to categorize patients. Kaplan-Meier analysis and Cox regression for disease-specific survival were stratified by SES. CDSS was calculated with simplified models. Logistic regression was conducted to identify risk factors for advanced stage at diagnosis, multimodal therapy, and diagnosis of squamous cell carcinoma.There were 3437 patients analyzed. In Cox models adjusting for patient-specific factors, the lowest SES tertile exhibited worse mortality (hazard ratio, 1.22; 95% CI, 1.07-1.39;Lower SES is associated with worse outcomes in paranasal sinus cancer. Research should be devoted toward understanding factors that contribute to such disparities, including tumor pathology and treatment course.

The Food and Drug Administration and the National Institutes of Health (NIH) have asserted that diverse demographic representation in clinical trials is essential. In light of these federal guidelines, the objective of this study is to assess the racial, ethnic, and gender demographics of patients enrolled in clinical trials registered with the NIH that evaluate chronic rhinosinusitis with nasal polyposis (CRSwNP) relative to the demographics of the US population.Cross-sectional study.Not applicable.ClinicalTrials.gov was queried to identify all prospective clinical trials for CRSwNP. Individual study and pooled data were compared with national US census data.Eighteen studies were included comprising 4125 patients and evaluating dupilumab, mepolizumab, omalizumab, fluticasone/OptiNose, MediHoney, mometasone, and SINUVA. Women constituted 42.7% of clinical trial participants. Of the 4125 participants, 69.6% identified as White, 6.6% as Black, 20.8% as Asian, 0.1% as Pacific Islander, 0.4% as American Indian, 8.0% as Hispanic, and 2.4% as other. The racial, ethnic, and gender composition of the pooled study population differs significantly from national US census data, with underrepresentation of Black, Hispanic, Pacific Island, and American Indian individuals, as well as females (The racial, ethnic, and gender demographics of patients enrolled in CRSwNP clinical trials registered with the NIH differ significantly from the demographics of the US population, despite federal guidelines advising demographically representative participation. Proactive efforts to enroll participants that better represent anticipated treatment populations should be emphasized by researchers, institutions, and editorial boards.

Background The management of paranasal sinus and nasal cavity malignancies has evolved significantly with the development of advanced endoscopic techniques and improvements in adjuvant therapy. We sought to characterize both disease-specific survival (DSS) and 5-year conditional disease-specific survival (CDSS, the change in life expectancy with increasing survivorship) for sinus malignancies diagnosed before and after the year 2000. Methods Patients diagnosed with sinus and nasal cavity cancer between 1973-2015 were extracted from the Surveillance, Epidemiology, End Results (SEER) registry. Kaplan-Meier analysis for DSS was stratified by year of diagnosis before and after 2000. Cox-proportional hazards models of DSS controlling for stage, age, and year of diagnosis were generated. CDSS was calculated using Cox-regression models stratified by stage. Results We analyzed 10,535 patients. Diagnosis after the year 2000 was independently associated with improved DSS (HR:0.81, 95% CI: 0.75-0.87, P Conclusion For paranasal sinus and nasal cavity malignancies, year of diagnosis independently influences both DSS and CDSS. Improved survival is likely due to advances in both surgical and adjuvant treatments. To our knowledge, this study is the first to examine CDSS for these malignancies.

Background Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator for cystic fibrosis (CF) patients homozygous or heterozygous for F508del. Effects of the drug on sinonasal symptoms have not been studied. Methods Adult participants were prospectively evaluated at baseline and after three months of treatment using validated questionnaires assessing sinonasal symptoms (SNOT-22) and CF-related quality of life (CFQ-R). Results Forty-three participants completed the study; 23 were taking other CF transmembrane conductance (CFTR) modulators at the time of study participation. There was a significant improvement in mean SNOT-22 from 34.8 (29.4–40, 95% confidence interval) to 24.4 (19.9–29.0) (p = 0.000003) and in the Respiratory domain of the CFQR from 60.6 (57.1–64.1) to 83.3 (79.4–87.2) (p = 0.0000002), both achieving a minimal clinically important difference. Patients previously taking CFTR modulators experienced a greater benefit in sinonasal and respiratory symptoms. Conclusions Elexacaftor-tezacaftor-ivacaftor is associated with significant improvement in sinonasal symptoms; previous use of CFTR modulators is associated with greater benefit.

Critical review of computed tomography (CT) imaging is essential in preoperative planning for endoscopic sinus surgery. In this study, we used a systematic review and a modified Delphi method to develop a comprehensive checklist that facilitates preoperative review of sinus CT imaging.We performed a systematic review of PubMed, Embase, CINAHL, Cochrane, and Web of Science databases to identify existing checklists developed to evaluate sinus CT imaging. An inclusive list of items from these checklists was compiled and a modified Delphi methodology was used to assign ranked priority. The Delphi process involved 14 rhinologists and had three phases: an initial survey with Likert priority (scale of 1-9) and two rounds of live discussions followed by survey to confirm consensus.Ninety-seven possible checklist items were identified from a systematic review and panelist input. On initial survey, 63 items reached a consensus score of 7+, and 13 items had near consensus scores between 6 and 7; two of these 13 borderline items were retained after subsequent panelist discussion. The resulting items were consolidated into an 11-item disease checklist and a 24-item anatomical checklist; the anatomical checklist was further divided into six subsections: nasal cavity, maxillary, ethmoid, sphenoid, frontal, skull base, and orbit. Additionally, panelists identified six core aspects of patient history to consider prior to surgery.After establishing content validity through a systematic literature review and a modified Delphi method, we developed a comprehensive checklist for preoperative sinus CT imaging review; implementation and evaluation of validity among trainees will suggest overall utility.

Background: Understanding patient-specific risk factors for complications of functional endoscopic sinus surgery (ESS) is critical. Previous work has investigated such risk factors, but a population-based analysis has not been performed to date. Objectives: This study analyzes the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to identify patient-specific risk factors associated with complications following ESS. Methods: A retrospective cohort study of patients who underwent ESS was conducted using the NSQIP database from 2011 to 2017. Patients were identified using CPT-codes for ESS procedures. The primary outcome analyzed was any postoperative complication. Simultaneous procedures with ESS were controlled for with regression analysis. Post-operative complications and 30-day readmission were evaluated using multivariate logistic regression controlling for age, gender, race, comorbidities (diabetes mellitus, hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, steroid use, and cancer history), smoking history, and intraoperative factors. Results: A total of 1279 patients who underwent ESS were identified. The average age of patients was 46.1 (SD = 16.8). Most patients (58.2%) had no major comorbidities. 594 (46.4%) patients had a tonsillectomy, adenoidectomy, or uvulopharyngoplasty at the same time as ESS. 101 (7.9%) patients experienced a complication post-operatively. 46 (3.6%) patients experienced a readmission postoperatively. The most common complication was reoperation (N = 40, 3.1%). Regression analysis revealed that gender was the only demographic factor associated with risk of post-operative complications, with women having a significantly lower risk than men (OR = 0.61, 95% CI 0.37-0.99, P = .046). Conclusions: ESS is typically performed on a relatively young and healthy population. Women have a significantly lower risk of complications after controlling for comorbidities. Further analysis of gender-specific differences in surgical outcomes should be evaluated to understand this phenomenon.

BACKGROUND The vascularized nasoseptal flap (NSF) is a pillar of contemporary endoscopic skull base reconstruction. The pedicle for the NSF is supplied by the posterior septal branch of the sphenopalatine artery, which courses along the arch of the choana and sphenoid rostrum before entering the nasal septum. Resection or mobilization of this region is necessary for surgical access to the clivus. OBJECTIVE To describe a technique for preserving bilateral NSF pedicles during endoscopic endonasal resection of the clivus, thereby safeguarding availability of the flaps for future skull base repair needs. METHODS Report of operative technique with video demonstration. RESULTS This technique for NSF preservation allows for wide access to the clivus while saving the future option for vascularized flap repairs of skull base defects. The patient in whom we demonstrate this technique underwent complete resection of her clivus without cerebrospinal fluid leak and with preservation of both NSF pedicles. CONCLUSION The "rescue strip" technique for endonasal endoscopic clival surgery preserves the bilateral NSF pedicles for future use without compromising surgical access to the clivus.

SUMMARYSARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. While SARS-CoV-2 exceeded IAV in its capacity to cause injury to the lung and kidney, the most significant changes were observed in the olfactory bulb (OB) and olfactory epithelium (OE) where inflammation was visible beyond one month post SARS-CoV-2 infection. Despite a lack of detectable virus, OB/OE demonstrated microglial and T cell activation, proinflammatory cytokine production, and interferon responses that correlated with behavioral changes. These findings could be corroborated through sequencing of individuals who recovered from COVID-19, as sustained inflammation in OB/OE tissue remained evident months beyond disease resolution. These data highlight a molecular mechanism for persistent COVID-19 symptomology and characterize a small animal model to develop future therapeutics.

Background Elexacaftor/tezacaftor/ivacaftor is a highly effective modulator that improves function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in improved pulmonary function in patients with cystic fibrosis (CF). We hypothesize that improvements in lung function are associated with improvements in health-related quality of life and sinonasal health. The aim of this study is to measure the effect of elexacaftor/tezacaftor/ivacaftor on patient-reported sinonasal and overall quality of life, and to determine the relationship between changes in these 2 outcome measures. Methods A prospective cohort study was conducted at an accredited adult CF care center. Participants completed the 22-item Sino-Nasal Outcome Test (SNOT-22) and the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a validated patient-reported outcome metric for CF patients, at baseline and at 3 months after initiation of elexacaftor/tezacaftor/ivacaftor. Results Forty-three individuals completed the study. There was significant improvement in nearly all domains of the SNOT-22 and CFQ-R after 3 months of therapy. SNOT-22 improved from 34.8 to 24.4 (p = 0.000003). Mean baseline FEV-1 improved from 65% to 76% predicted (p = 0.0000005). The greatest effect was seen in those participants previously taking modulator therapy. Linear regression between the change in SNOT-22 individual domains and the CFQ-R respiratory domain revealed the strongest correlation between the extranasal domain score and the respiratory domain of the CFQ-R (R2 = 0.24). Conclusion CF patients taking elexacaftor/tezacaftor/ivacaftor experience a significant improvement in both sinonasal and health-related quality of life.

Patients with aspirin exacerbated respiratory disease (AERD) experience a severe and recalcitrant form of chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma, which are exacerbated by aspirin/NSAID ingestion. As compared with aspirin-tolerant CRSwNP, patients with AERD experience more severe olfactory dysfunction, which is one of the key contributors to the observed decrease in quality of life (QOL) in this disease. The objective of this paper is to review the published olfactory outcomes observed with various treatment modalities.

This paper reviews the current management of craniopharyngioma tumors with a focus on surgical treatment options. Advances in transnasal endoscopic skull base surgery and proton therapy have altered the management options available for this challenging condition. Craniopharyngiomas are benign suprasellar tumors that originate from Rathke’s pouch. These complex lesions may cause major neurologic, endocrine, and visual deficits. Treatment modalities include endoscopic transnasal versus open transcranial surgery to achieve gross total or subtotal resection. Various forms of radiation therapy are often integral to comprehensive management of craniopharyngiomas. This article reviews current treatment modalities and surgical risks, highlighting differences between endoscopic versus transcranial surgical approaches.

Pediatric skull base lesions are complex and challenging disorders. Safe and comprehensive management of this diverse group of disorders requires the expertise of an experienced multidisciplinary skull base team. Adult endoscopic skull base surgery has evolved due to technologic and surgical advancements, multidisciplinary team approaches, and continued innovation. Similar principles continue to advance the care delivered to the pediatric population. The approach and management of these lesions varies considerably based on tumor anatomy, pathology, and surgical goals. An understanding of the nuances of skull base reconstruction unique to the pediatric population is critical for successful outcomes.

Background The pterygopalatine fossa (PPF) contains numerous important neurovascular structures; notably, the sphenopalatine ganglion (SPG), the maxillary branch of the trigeminal nerve (V2), and the internal maxillary artery. With the advent of extended endoscopic endonasal surgery, the surgical anatomy of the PPF warrants increased investigation. Intraoperative dissection and preservation of the SPG is essential to prevent postoperative xeropthalmia and facial hypoesthesia. Objective This study aims to (1) describe a novel dissection technique for identifying the SPG and (2) define the SPG location relative to the sphenopalatine foramen (SPF), which is a consistently identifiable landmark. Methods Eight cadaveric PPFs were dissected in step-wise fashion. An endoscopic medial maxillectomy was performed, the SPF was identified, and the posterior maxillary wall was resected. The maxillary branch of the trigeminal nerve (V2) was identified anterolaterally in its infraorbital canal and traced medially to identify the pterygopalatine nerve to the SPG. The lateral distance and superior/inferior distance from the SPG to the fixed SPF was measured. Results The surgical technique described allowed for reliable identification of the SPG. The SPG was located on average 4.5 ± 1.1 mm lateral and 1 ± 1.4 mm inferior to the SPF. Conclusion Identification and preservation of the SPG is necessary to prevent complications in endoscopic endonasal PPF surgery. The SPG can be reliably located near the SPF by following the pterygopalatine nerve branch of V2.

Background The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office-based endoscopic sinus procedures performed under local anesthesia. Methods We conducted a prospective study of adults undergoing in-office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5-minute intervals throughout the procedure. Anxiety levels were scored using the State-Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric. Results Twenty-five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mmHg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mmHg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred. Conclusion Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.

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)-β1 levels between smokers and non-smokers., Graphical Abstract, Nakayama et al. discover key variabilities in expression of SARS-CoV-2 entry factors among human head and neck mucosal tissues. They demonstrate that SARS-CoV-2 preferentially infects the nasal cavity and trachea. They uncover an association between smoking and higher SARS-CoV-2 in the human proximal airway, in part because of differences in IFN-β1 expression.

Objective Smell and taste alteration are closely linked to infection with SARS-CoV-2 and may be associated with a more indolent disease course. Serologic response rates among individuals with mild disease remains limited. We sought to identify whether chemosensory changes associated with COVID-19 were predictive of a serologic response. Study design Cross-sectional study. Methods The sample consisted of 306 adults (≥18 years old) volunteering for convalescent plasma donation following perceived COVID-19 illness from April-June 2020. Documentation of COVID-19 PCR status, clinical symptoms at time of illness, and treatment course occurred at the time of serologic analysis, where we assessed chemosensory function using patient-perceived deficits. We implemented previously validated ELISA screening to determine serologic status regarding anti-Spike immunoglobulins. Statistical analysis using stepwise logistic models were employed to identify predictive factors of serologic response. Results Of 306 patients undergoing serologic and chemosensory evaluation, 196 (64.1%) and 195 (63.7%) reported subjective olfactory and taste dysfunction, respectively, during the first two weeks of COVID-19 infection. In unadjusted models, the odds of developing suprathreshold IgG antibody titers were 1.98 times higher among those who reported altered smell (95% CI 1.14–3.42, p = 0.014) and 2.02 times higher among those with altered taste (95% CI 1.17–3.48, p = 0.011) compared to those with normal smell and taste. Multivariable logistic models adjusting for sex, age, race/ethnicity, symptom duration, smoking status and comorbidities index demonstrated that altered smell and taste remained significant predictors of positive anti-spike IgG response (smell OR = 1.90, 95% CI 1.05–3.44, p = 0.033; taste OR = 2.01, 95% CI = 1.12–3.61, p = 0.019). Conclusion Subjective chemosensory dysfunction, as self-reported smell or taste deficiency, is highly predictive of serologic response following SARS-CoV-2 infection. This information may be useful for patient counseling. Additional longitudinal research should be performed to better understand the onset and duration of the serologic response in these patients.

Objectives: Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reducing CRS symptom burden. This study seeks to evaluate the role of patient-reported quality-of-life measures in guiding interventions for CF-related sinus disease. Methods: We performed a prospective, cross-sectional study of 105 patients presenting to a CF-accredited clinic between July and September 2018. Demographic data and sinus surgery history were collected, in addition to Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Disorders (QOD-NS) scores. Statistical analysis was conducted using correlation and non-parametric Mann-Whitney U tests. Results: Baseline well-care visits accounted for 71.4% of all clinical evaluations. Prior otolaryngology intervention was noted in 69 (66%) patients, where the majority of these patients (63/69; 91%) underwent endoscopic sinus surgery (ESS). Patients with a history of otolaryngology intervention had an average SNOT-22 score of 33.2 (SD = 20.6) compared to 24.9 (SD = 18.5) for patients without prior intervention ( P = .048). The average QOD-NS score was 5.5 (SD = 6.4) among patients referred to otolaryngologists and 3.1 (SD = 5.7) for non-referred patients ( P = .012). SNOT-22 and QOD-NS scores were modestly correlated ( R of .43). Conclusion: CF patients with symptoms resulting in worse quality-of-life assessments were more likely to have established coordinated care with an otolaryngologist. Further validation of the utility of SNOT-22 and QOD-NS questionnaires as care coordination metrics is necessary in the CF population.