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RNA expression signatures of ONB from Classe et al., 2018 based on markers traditionally associated with sinonasal undifferentiated carcinoma (A), small cell neuroendocrine carcinoma (B), and olfactory neuroblastoma (C), divided by control OE, low grade ONB, high grade ONB, and IDH2 mutant ONB. A) Expression of keratins is not significantly increased in IDH2 mutant ONB versus IDH2 wild type tumors. B) Small cell neuroendocrine carcinoma (SNEC) marker genes are not highly expressed ONB from Classe et al. dataset. C) Expression of canonical neuroendocrine markers is negatively associated with ONB grade, and is not significantly different between high grade IDH2 and high grade IDH2 mutant ONB.

Tumor demographics separated by Hyams grade, Dulguerov T stage, and gene expression groups (low versus high) used for survival analysis in Figure 5 and Figure S4. Average Ki-67 mRNA expression obtained from bulk RNA-Seq outputs. Average Ki-67 index obtained from histology data reported by Classe et al., 2018. +/- in the last two columns is standard error of the mean (SEM).

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Due to the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-Sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-Sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T cell identities in high grade tumors (GBC from approximately 0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman’s gland, and olfactory ensheathing programs, in high grade tumors (mature neuronal from 3.7% to approximately 0%, Bowman’s gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-Sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression.

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Due to the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-Sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-Sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T cell identities in high grade tumors (GBC from approximately 0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman’s gland, and olfactory ensheathing programs, in high grade tumors (mature neuronal from 3.7% to approximately 0%, Bowman’s gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-Sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression.

Although the majority of patients with sinus headache do not have rhinosinusitis, many patients will unnecessarily undergo work-up and treatment for rhinosinusitis. This leads to a significant cost burden to the healthcare system. In the era of value-based care, more effective management paradigms need to be developed for sinus headache.Recent efforts to classify nonrhinogenic headache, namely the International Classification of Orofacial Pain, have served as an important step in advancing our understanding of this heterogeneous condition. In addition, a review of the literature points to certain clinical features that may allow for the identification of nonrhinogenic headache based on history.A greater understanding of nonrhinogenic headache as well as innovative tools to differentiate rhinogenic from nonrhinogenic headache are needed to change the paradigm in the management of patients with sinus headache.

Background Endoscopic sinus surgery is a well-established treatment for chronic rhinosinusitis in patients with cystic fibrosis, though its benefits seem to be limited to improving sinonasal symptoms rather than affecting lung function. Objective This study aims to identify clinical and demographic factors that may influence sinonasal and pulmonary outcomes after surgery. Methods This is a six-year retrospective analysis of adult cystic fibrosis patients who underwent endoscopic sinus surgery at a tertiary care center. 22-Item Sino-Nasal Outcomes Test scores and mean forced expiratory volume data at baseline and three to six months after surgery were analyzed using t-test and stepwise regression with the following covariates: age, gender, lung transplant, revision surgery, and pseudomonas on sinus culture. Results 119 surgeries were performed on 88 patients, with 69% on patients with transplant. The overall mean (Standard Deviation) improvement in 22-Item Sino-Nasal Outcomes Test score was 9.42 (18.15) for the entire cohort ( P Conclusion Although surgery was associated with a clinically and statistically significant improvement in sinonasal scores in cystic fibrosis patients, patients with pseudomonas may experience less benefit. Revision surgery and older age may be associated with less favorable pulmonary outcomes. Awareness of such variables may help when deciding which cystic fibrosis patients should undergo surgery.

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207 + dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.

Primary Ig deficiencies are a heterogeneous group of disorders with widespread implications for the unified airway. Manifestations can vary greatly, with some patients being asymptomatic, whereas others suffering from acute and chronic life-threatening pathologic conditions of the upper and lower airways. Although the diagnosis of PIDs can be complex, the onus of early diagnosis and initiation of treatment will often fall on the shoulders of the otolaryngologist.

Background Squamous cell carcinoma of the nasal cavity (NCSCC) is a rare, challenging malignancy. Surgical resection of this tumor can cause significant facial deformity, and indications for adjuvant or organ preservation therapies are not well-described. Objective To examine the impact of treatment regimen on survival outcomes in NCSCC and to compare surgical to non-surgical based therapies. Methods The National Cancer Database was queried for NCSCC from 2004 to 2014. Patient demographics, tumor characteristics, and treatment regimen were compared for the entire cohort. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen and surgical margins on overall survival (OS) for early and late-stage disease. Results A total of 1883 NCSCC patients were identified. The OS for the cohort was 83 months, and median age at diagnosis was 65 years. NCSCC patients who underwent surgery followed by adjuvant radiation therapy (RT) had a better OS compared to definitive RT (HR: 0.58, P Conclusions NCSCC appears to be best treated with surgery followed by adjuvant RT in advanced-stage disease whereas in early-stage disease, surgery does not improve OS compared to definitive RT.

Objectives This article describes a novel technique implementing the use of a tympanostomy t-tube to provide long-term marsupialization of small Rathke's cleft cysts (RCCs). Design A retrospective review of electronic medical records was performed to collect demographic and clinical data on a series of four patients. Setting Academic medical center. Participants Four female patients (mean age of 34 years) underwent transsphenoidal endoscopic endonasal surgery for RCC. All four patients presented with headaches. Mean cyst size was 7 mm. Two of the four surgeries were revisions for RCC recurrence. Main Outcome Measures Symptom resolution after surgery, duration of follow-up, and feasibility of the proposed technique. Results Tympanostomy t-tube was used to marsupialize small RCCs (< 10 mm) for four patients. Three patients remained symptom-free with endoscopy and imaging showing patent t-tubes at 21 months' (range 20–24 months) follow-up. One patient experienced severe migraines immediately after surgery. Migraines were relieved after t-tube was removed 6 weeks after surgery. Conclusion Tympanostomy t-tubes placed via an endoscopic endonasal approach can provide long-term marsupialization for small RCCs.

Objectives: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)−22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP). Methods: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared. Results: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose ( P Conclusions: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.

SummaryMost human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE). This approach reveals that the OE of patients with persistent smell loss harbors a diffuse infiltrate of T cells expressing interferon-gamma; gene expression in sustentacular cells appears to reflect a response to inflammatory signaling, which is accompanied by a reduction in the number of olfactory sensory neurons relative to support cells. These data identify a persistent epithelial inflammatory process associated with PASC, and suggests mechanisms through which this T cell-mediated inflammation alters the sense of smell.

Background Endoscopic sinus surgery (ESS) is an effective intervention for patients with medically refractory chronic rhinosinusitis. Frontal sinusotomy is the most challenging part of ESS, with one of the key outcomes being access for topical irrigations. Objective The purpose of this study is to compare irrigation penetration into the frontal sinus following Draf IIa versus modified Draf IIa frontal sinusotomy. Methods Four fresh cadaver heads were used in this experiment. Draf IIa was performed on one side of each head and a modified Draf IIa on the contralateral side. This proposed modification consists of a Draf IIa combined with an agger nasi punch-out procedure and partial trimming of the vertical lamella of the middle turbinate back to the posterior table of the frontal sinus without drilling the beak. Each head was irrigated with methylene blue-dyed water and recorded by rigid endoscopy through an endonasal view (EV) of the frontal sinus and frontal trephination view (TV). Two blinded rhinologists scored the extent of staining (using an ordinal scale of 0 to 3) for each side. A case report where the modified Draf IIa was performed is also described. Results After modified Draf IIa sinuosotomy, the mean score for the EV was 2.125 and for the TV was 2, versus 0.875 and 0.625 for traditional Draf IIa, respectively. There was a statistically significant increase for both EV (p = 0.019) and TV (p = 0.018) after modified Draf IIa. Conclusion In our cadaveric model, this procedural modification improved penetration of postoperative irrigations into the frontal sinus. This simple technique may be easily adapted into frontal ESS when indicated.

Background Recent studies have demonstrated a dramatic increase in the use of balloon sinus dilation (BSD) in the United States. However, the use of BSD specifically in revision sinus surgery has not been investigated. This study addresses the question of how BSD is utilized as a tool in revision sinus surgery. Methods Data from MarketScan (Truven Health) over a 5-year period (2012-2016) were analyzed. Patients who underwent a sinus procedure with a minimum of 2 years of follow-up were included. Results A total of 62,304 patients met inclusion criteria; 6847 (10.99%) underwent revision. Age >55 years, the South geographical region, and medical comorbidities increased the odds of revision on multivariate analysis. For patients undergoing revision, BSD was used 11%, 21%, and 13% of the time for revisions of the maxillary, frontal, and sphenoid sinuses, respectively. For a sinus that underwent revision after an initial BSD, a repeat BSD was done close to 40% of the time. Conclusion BSD is used frequently in the revision setting, especially for the frontal sinus and for patients who had already undergone an initial BSD. Our findings highlight the prevalent role of BSD in revision surgery and the need to evaluate such practices.

Objectives: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP). Methods: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups. Results: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores ( P = .244). The CSF rhinorrhea group improved more in runny nose ( P Conclusions: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.

Presbyosmia, or aging related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) in the nasal fossa is the peripheral organ for olfaction, and is subject to acquired damage, suggesting a likely site of pathology in aging. OE basal stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis or repair. Accordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. Combining psychophysical testing with olfactory mucosa biopsy analysis, single cell RNA-sequencing (scRNA-seq), and human olfactory culture studies, we identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress, or the regulation of proliferation and differentiation. To facilitate further study of human OE stem cells, we developed an adult human basal cell culture model. Characterization of cultures using scRNA-seq confirmed maintenance of a reserve stem cell-like phenotype, and brief cytokine exposure in basal cell cultures resulted in increased expression of TP63, a transcription factor acting to prevent OE stem cell differentiation. Our data are consistent with a process by which aging-related inflammatory changes in OE stem cells may contribute to presbyosmia, via the disruption of normal epithelial homeostasis, suggesting that OE stem cells may represent a rational therapeutic target for restoration of olfaction.One Sentence SummarySingle cell profiling suggests that inflammatory-associated olfactory epithelial stem cell dysfunction is associated with presbyosmia in humans.

Objectives: Patients with undiagnosed obstructive sleep apnea (OSA) often present to an otolaryngologist with symptoms of chronic rhinosinusitis (CRS). This study analyzes symptom profiles of such patients to help identify those who may benefit from polysomnography. Methods: This is a 2-year retrospective analysis of adult patients at an academic practice with a rhinologic chief complaint. Results of the 22-Item Sinonasal Outcomes Test (SNOT-22) were compared between patients with untreated OSA without CRS (OSA group) and a control group of CRS patients (CRS group). Univariate analysis with Bonferroni correction and multiple logistic regression were used. Results: Forty-one patients were included in the OSA group (mean apnea-hypopnea index = 28.8, SD = 21.0) and 124 patients in the CRS group. CRS group demonstrated higher scores in nasal, extra-nasal, and ear/facial symptom domains ( P < .001), while OSA group displayed higher psychological ( P = .020) and sleep domain scores ( P = .048). Nasal discharge ( P < .001) and loss of smell/taste ( P = .004) scores were higher in CRS group, whereas facial pain ( P = .285) and nasal obstruction ( P = .822) were not significantly different. On logistic regression, thick nasal discharge, loss of smell/taste, and ear pain were predictive of CRS, while waking up tired was predictive of OSA. Finally, OSA group was more likely to choose a sleep-related issue as a most important symptom (MIS) ( P < .001). Conclusions: OSA and CRS have significant overlap in symptom profiles. The SNOT-22 can help identify those with undiagnosed OSA. OSA should be suspected in patients who report a sleep-related item as a MIS and display higher psychological and sleep domain scores.

Objectives/hypothesis Responsible prescribing of postoperative pain medications is necessary in combatting the current opioid epidemic in the United States. The goal of this study was to determine which clinical factors affect opioid usage following functional endoscopic sinus surgery (FESS). Study design Retrospective medical records study. Methods This is a single-institution retrospective study of subjects undergoing FESS by the senior author between September 2016 and December 2017. Opioid usage was assessed for each patient at the first postoperative visit. Univariate and multivariable analyses were performed to investigate factors associated with pain medication usage. Patients using opioids prior to surgery were excluded. Results A total of 136 patients were stratified into three groups based on number of opioid tablets taken during the first week after surgery: 31 patients (23%) took no opioids, 61 patients (45%) took one to five tablets, and 44 patients (32%) took more than five tablets. Gender, extent of surgery, revision surgery, polyp status, and cystic fibrosis did not significantly vary between the three groups. Multinomial logistic regression analysis with backward stepwise variable selection method revealed that those who had septoplasty (odds ratio [OR]: 4.84, 95% confidence interval [CI]: 1.68-13.98; P 5 tablets. Conclusions The majority of patients undergoing FESS did not take more than 5 opioid tablets after surgery. Concurrent septoplasty and younger age were associated with increased opioid usage. Knowledge of such factors can help surgeons to assess opioid prescribing patterns and to counsel their patients on postoperative pain. Laryngoscope, 129:1751-1755, 2019.

Background In-office balloon sinus dilation (BSD) has recently gained popularity as a surgical treatment option for chronic rhinosinusitis (CRS). However, utilization, indications, and practice patterns surrounding in-office BSD remain unclear. Objective The purpose of this study was to use a large national administrative database to assess preoperative management of CRS prior to in-office BSD. Methods Patients undergoing standalone in-office BSD from 2011 to 2014 were identified on MarketScan and compared to a control group undergoing functional endoscopic sinus surgery (FESS). Visits to the otolaryngologist, number of computed tomography (CT) scans, number of antibiotic and steroid prescriptions, and duration of time from first visit to procedure were compared. Results When compared to the FESS group, the in-office BSD group overall had fewer office visits (2.0 vs 2.2), CT scans (1.0 vs 1.1), prescriptions for antibiotics (2.0 vs 2.2), prescriptions for systemic steroids (1.5 vs 1.8), and topical steroids (1.4 vs 1.5) in the preoperative period. They also had a shorter mean duration of time between first visit and CT scan (17.5 vs 21.4 days) as well as between first visit and procedure (55.0 vs 67.8 days). All of these findings were statistically significant. Conclusion In-office BSD for CRS was overall associated with less intense management in the preoperative period when compared to FESS. Such differences may reflect ongoing shifts in practice patterns and need to be further investigated.

Objectives: Chronic rhinosinusitis (CRS) is a common and costly health problem in the United States. While often associated with younger adults, CRS can affect the elderly. As the aging population increases in the United States, the cost burden of CRS in older adults is important to assess. The objective of this study is to characterize healthcare resource utilization (HCRU) and healthcare expenditure (HCE) for CRS in this population. Methods: Patients meeting criteria for CRS with three years of continuous data were identified on IBM® Marketscan Research Databases over a five-year period (2013–2017). Medication utilization, outpatient visits, surgery, and expenditures related to CRS were assessed for older adults (&gt, 65) and compared with other age groups. As a secondary analysis, multivariable generalized linear models were utilized to compare HCE while adjusting for baseline medication utilization. Results: A total of 238,825 patients met the inclusion criteria, of which 20,927 were older adults. Older adults had the highest overall prevalence of nasal polyps (10%) and asthma (16%) among adult groups. Surgery rate was lower than other adult groups, but medication utilization was the highest. Mean overall HCE at two years was highest in older adults (USD 2545 vs. 2298 in young adults). However, HCE was highest for the young adult group after adjusting for baseline medication usage. Conclusion: Older adults had a higher rate of CRS-related co-morbidities as well as the highest CRS-related medication utilization and unadjusted two-year HCE. Although the reasons for this are unclear, possibilities include greater disease severity and preference for medical versus surgical management. HCE for CRS is expected to increase as the aging population grows.

The management of chronic rhinosinusitis (CRS) by a nonotolaryngologist prior to otolaryngology referral is an important component of the patient care pathway. The purpose of this study is to characterize CRS management during this period and to identify areas of quality improvement.Retrospective review of a national claims database.Academic institution.Data were analyzed from the IBM Health MarketScan Research Databases (2013-2017). Patients with 3-year enrollment data were identified who were initially diagnosed with CRS by a nonotolaryngologist and subsequently seen by an otolaryngologist. Management of CRS by the nonotolaryngologist was assessed in terms of duration, demographics, health care resource utilization, and health care expenditure.A total of 51,273 patients met inclusion criteria. The median length of the referral period was 142 days, with variations according to geography. Patients with a delayed referral period had higher health care resource utilization in terms of visits for CRS (mean, 1.8 vs 1.2), total visits (mean, 12.6 vs 3.9), and medication prescriptions (especially antibiotics; mean, 5.8 vs 2.1). Health care expenditure was almost twice as high for the delayed referral group (mean, $986 vs $571), mainly due to CRS-related medication costs (mean, $578 vs $214).Our findings suggest that there are wide variations in how CRS is managed prior to referral to an otolaryngologist. The dissemination of clinical practice guidelines to primary care providers may help to increase efficiency of CRS care and offers a unique opportunity for quality improvement that extends beyond the bounds of our own specialty.

OBJECTIVES/HYPOTHESIS Chronic rhinosinusitis (CRS) is a common and costly health problem in the United States. A better understanding of healthcare resource utilization (HCRU) and healthcare expenditure (HCE) pertaining to CRS is required. The objective of this study is to investigate geographic variations in HCRU and HCE for CRS. STUDY TYPE/DESIGN Retrospective study of administrative database. METHODS Patients meeting pre-defined diagnostic criteria for CRS with continuous 1-year pre-index and 2-year post-index data were identified on IBM® Marketscan Research Databases over a 5-year period (2013-2017). Data pertaining to demographics, HCRU, and HCE were analyzed according to geographic region. Multivariable generalized linear models accounted for age, sex, baseline medication utilization, and co-morbidities. RESULTS About 237,969 patients were included. Antibiotics were the most commonly prescribed medication (95%). Surgery rate (11%), immunotherapy (9.2%), oral steroid use (66%), and antibiotic utilization (mean 6.3 prescriptions) were highest in the South. However, visits with an otolaryngologist were considerably higher in the Northeast (62%). The Northeast region had the highest mean HCE ($2,449), which was 13% greater than HCE for the North Central region ($2,172). HCRU and HCE were higher in urban areas across all metrics, with 2-year HCE being 18% greater in urban areas ($2,374 vs. $2,019). Significant geographic variation in HCE was observed even after adjusting for covariates. CONCLUSION Significant geographic variations in HCRU and HCE exist for CRS even after adjusting for covariates. Future studies are needed to help direct quality improvement and cost-saving efforts as well as efficient resource allocation in an era of value-based care. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2641-2648, 2021.

Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database.The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS).A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively).SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.

Objective Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database. Study design Retrospective database study. Methods The National Cancer Database was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics and tumor and treatment characteristics were tabulated. Kaplan-Meier (KM) analysis was performed to compare overall survival (OS) between histology subtype and primary site. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on OS. Results A total of 1,074 patients were identified. The maxillary sinus was the most common site (45%). T4 tumors were observed in 50% of patients, with most patients treated at high-volume facilities (77%). In KM analysis, spindle cell SCC histological subtype, primary tumors of the maxillary sinus, and poorly differentiated grade had worse OS. In our Cox-PH model, higher T stage and age were associated with worse OS. Those treated at a high-volume facility and those who underwent surgical resection followed by adjuvant radiation had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit except in surgical patients when positive margins were present, and surgery with adjuvant chemoradiation trended toward improved survival. Conclusions Sinonasal PDSCC appears to be best treated at high-volume centers with surgical resection followed by adjuvant radiation. Poorly differentiated grade has worse OS compared to more differentiated tumors. Chemotherapy along with adjuvant radiation may have a role in patients with positive surgical margins. Level of evidence 4 Laryngoscope, 131:E1040-E1048, 2021.

Background: Exposure to cigarette smoke has been associated with a higher incidence of postoperative complications across a variety of surgical specialties. However, it is unclear if smoking increases this risk after endoscopic sinus surgery (ESS). Because complication rates after ESS are relatively low, a large national database allows for a statistically meaningful study of this topic. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset from 2005 to 2016 was analyzed. Patients who underwent ESS were identified. Thirty-day postoperative complication rates between smokers and nonsmokers were compared. Complications included infection, thromboembolic events, reintubation, readmission, acute renal failure, and cardiovascular events. Results: 921 patients who underwent ESS were identified. 182 (20%) were smokers and 739 (80%) were nonsmokers. 609 patients underwent outpatient ESS, while 312 patients underwent inpatient ESS. A total of 12 patients experienced postoperative surgical site infections involving the deeper tissues beyond the wound (organ/space SSI). On univariate analysis, smoking was associated with a higher incidence of organ/space SSI ( P = .0067) and pulmonary embolism ( P = .0321) after ESS. On multivariate logistic regression, smoking was associated with increased odds (4.495, 1.11- 8.17, P = .0347) of organ/space SSI after ESS. Conclusions: This study demonstrates an association between exposure to cigarette smoke and potentially serious surgical site infections in the 30-day postoperative period after ESS. Our findings may help when counseling smokers who are considering ESS. Further study is required to understand the nature of these infections and ways to prevent them. Level of Evidence: 2c (“health outcomes”).

To determine whether treatment of sinonasal squamous cell carcinoma (SCC) at a high-volume facility affects survival.Retrospective database analysis.National Cancer Database (2004-2014).The National Cancer Database was queried for sinonasal SCC from 2004 to 2014. Patient demographics, tumor characteristics and classification, resection margins, treatment regimen, and facility case-specific volume-averaged per year and grouped in tertiles as low (0%-33%), medium (34%-66%), and high (67%-100%)-were compared. Overall survival was compared with Cox proportional hazards regression analysis.A total of 3835 patients treated for sinonasal SCC between 2004 and 2014 were identified. Therapeutic options included surgery alone (18.6%), radiotherapy (RT) alone (29.1%), definitive chemoradiation (15.4%), surgery with adjuvant RT (22.8%), and combinations (14.1%) of the aforementioned treatments. Patients who underwent surgery with adjuvant RT had better overall survival (hazard ratio [HR], 0.74;This study shows a better overall survival for sinonasal SCC treated at high-volume centers. Further study may be needed to understand the effect of case volume on the paradigms of sinonasal SCC management.

Although balloon sinuplasty (BSP) is increasing in popularity, little is known about which patients are the ideal candidates. The objective of this study is to investigate factors that may be associated with BSP failure.Retrospective review.Academic center.This is a 6-year (July 2011-June 2017) retrospective review of patients who underwent BSP or revision endoscopic sinus surgery (rESS) after BSP within a single tertiary health system. Demographics, clinical findings, and radiographic findings were investigated for association with rESS via univariate analyses and a multivariable backward elimination selection procedure.A total of 154 patients were identified (median age, 53 years): 146 patients underwent BSP at a single health system, with 16 (11%) undergoing rESS; 8 patients underwent BSP at an outside institution and underwent rESS with the senior author. Mean ± SD follow-up was 12.8 ± 16.6 months. Univariate analyses revealed that prior endoscopic sinus surgery, polyps, allergic rhinitis, and gram-negative infection were significantly associated with rESS. As for radiographic findings, a higher Lund-Mackay score, neo-osteogenesis, moderate or complete opacification, and hyperdensities were associated with rESS. The final model after multivariable selection showed that higher radiographic scores (odds ratio, 1.08; 95% CI, 1.01-1.17) and neo-osteogenesis (odds ratio, 5.25; 95% CI, 1.68-16.42) were associated with higher odds for rESS.This study identifies several clinical and radiographic factors that may be associated with the need for rESS after BSP. Surgeons can take these factors into consideration when deciding whether a patient should forego BSP and undergo conventional FESS.

Background Cancers of the paranasal sinuses are rare tumors that tend to be aggressive and usually are diagnosed at an advanced stage. Despite being rare, these tumors include a wide spectrum of histological subtypes with different biological behaviors. Choosing the optimal treatment modalities and analyzing the different oncological outcomes is therefore challenging. This study aims to evaluate the role of induction chemotherapy prior to definitive local therapy for sinonasal malignancies. Methods A systematic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. With the assistance of a medical librarian, data sources including MEDLINE, PubMed, Cochrane library, EMBASE, NCBI Bookshelf, National Guideline Clearinghouse, and Clinicaltrials.gov were searched using a customized search strategy that yielded 1758 articles. Inclusion criteria used were as follows: (1) the study has a patient population with 3 or more patients with previously untreated sinonasal malignancies; (2) patients underwent induction chemotherapy prior to definitive local therapy; (3) pretreatment staging information was documented; (4) overall survival was reported by histology type either in table or Kaplan-Meier format. Nine studies with 220 patients ultimately met inclusion criteria and were analyzed in groups based on tumor histology. Results For squamous cell carcinoma (SCC), the 5-year overall survival was 51%. For neuroendocrine tumors, the 5-year overall survival was 78%. Eighteen percent (18%) of patients with pretreatment orbital involvement ultimately underwent orbital exenteration. Conclusion Induction chemotherapy in the management of sinonasal malignancies has similar overall survival outcomes as other standard treatment modalities and can be offered as an option to patients as part of multimodality therapy.

Background Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. Methods This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. Results A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). Conclusion There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes.

Objective Recurrent acute rhinosinusitis (RARS) can be an elusive diagnosis due to the lack of clinical and radiographic findings in between acute episodes. This study aims to identify objective computed tomography (CT) characteristics in RARS. Study Design Case series with chart review. Setting Tertiary academic medical center. Subjects and Methods Patients meeting diagnostic criteria for RARS were identified retrospectively from the senior author's practice. Patients were diagnosed with RARS if they experienced 3 or more episodes of acute sinusitis within the past year with complete resolution of symptoms in between episodes. At least 1 episode was confirmed via CT or endoscopy. CT scans showing prior surgery were excluded. The scans for these patients were compared with those from a normal control group. Bone radiodensity of the entire ostiomeatal complex (OMC), including the ethmoid bulla, middle turbinate, and uncinate, was measured in Hounsfield units. Maximum radiodensity was noted for each side. Results A total of 16 patients meeting inclusion criteria for RARS were compared with 16 healthy patients. The mean Lund-MacKay score was 1.6 in the RARS group and 1.3 in the control group. The maximum radiodensity of the OMC was significantly higher in the RARS group (556) compared with that of the control group (327) ( P < .0001). Conclusion Patients with RARS had significantly greater radiodensity of the OMC compared with those in the control group despite minimal differences in mucosal disease. Radiodensity measurement of the OMC using Hounsfield units may help to identify patients with this elusive diagnosis.

Background Patients with cystic fibrosis (CF) who have undergone lung transplantation frequently require hospitalizations and antibiotic treatments for respiratory tract infections. Although endoscopic sinus surgery (ESS) improves sinonasal quality of life in CF patients, it is unclear if ESS offers additional benefit in terms of antibiotics for pulmonary infection, hospitalization, and pulmonary function. Objective To determine whether ESS impacts antibiotic use or hospitalizations for pulmonary indications or pulmonary function in CF patients after lung transplantation. Methods This is a single-institution retrospective study of all patients who underwent lung transplantation for CF from 2005 to 2017. Patients who underwent ESS at least 1 year after transplant were included. Paired bivariate analyses were performed to determine whether there was a difference in the frequency and length of hospitalizations for pulmonary indications, number of antibiotic courses (intravenous and oral) for pulmonary exacerbations, and forced expiratory volume in 1 second (FEV1) slope in the 6 months before versus after ESS. Perioperative antibiotics and hospitalizations were not included in the analyses. Least squares regression was utilized to analyze FEV1 trends. Results A total of 20 patients underwent 36 ESS during the study period. There was significantly higher antibiotic utilization in the 6 months before ESS (0.89 ± 1.03) compared to the 6 months after ESS (0.33 ± 0.53) ( P = .002). The frequency and length of hospitalizations, FEV1 slope, and FEV1 trend before and after ESS were not significantly different. Conclusion Our results suggest that ESS is associated with a reduction in the frequency of antibiotic utilization for respiratory tract infections in lung transplant recipients with CF. A prospective study is needed to investigate these relationships further.