Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Surgical Correction of an Extensive Skull Base Defect as a Result of Pneumocele.

Pneumocele is a condition involving the pathologic expansion of paranasal sinuses with corresponding bony erosion of the skull base. Extensive pneumocele can lead to pneumocephalus, especially in patients with long-term cerebrospinal fluid shunts. Here, the authors present a case of pneumocele in an adult with a history of congenital hydrocephalus managed with a ventriculoperitoneal shunt. The patient underwent reconstruction of a posterior table defect with a pericranial flap followed by frontal sinus obliteration with abdominal fat.

The effect of smoking on quality of life following sinus surgery: 10-year follow-up.

OBJECTIVES: The purpose of this study is to investigate the 10-year postoperative quality of life outcomes in smokers and nonsmokers with chronic rhinosinusitis. STUDY DESIGN: This is a single-institution prospective cohort study. METHODS: 235 patients who have previously been enrolled in a 4-year follow-up study were identified and contacted for a telephone interview. Rates of revision surgery, smoking status and 20-item sinonasal outcomes test (SNOT-20) scores were obtained. Preoperative SNOT-20 scores were compared with those obtained at the 10-year follow-up. RESULTS: Of the patients enrolled in the initial 4-year study, 22.5% were available for a telephone interview, including 43 out of 185 nonsmokers (23.2%) and 9 out of 50 smokers (18%). Demographic data including age, sex and race were analyzed and found to be similar between the two groups. Preoperative SNOT-20 scores were similar between nonsmokers and smokers (28.9 vs. 25.8, p = 0.89). There was no significant difference in long-term SNOT-20 scores (10 years postoperatively) between nonsmokers and smokers (31.5 vs. 28.2, p = 0.629). CONCLUSIONS: While cigarette smoke may have long-term adverse effects on the sinonasal mucosa, we found no difference in quality of life outcomes between smokers and nonsmokers 10 years after functional endoscopic sinus surgery.

Predictors of Non-Rhinogenic Facial Pain or Pressure in Otolaryngology Clinic.

OBJECTIVES: Identify demographic and clinical characteristics that may help differentiate non-rhinogenic facial pain or pressure (NRFP) from sinusitis. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary Care Center Rhinology Clinic. METHODS: All patients presenting with a complaint of facial pain or pressure over a 3-year period were included. Patients were categorized into either NRFP or sinusitis groups based on computed tomography imaging and nasal endoscopy. Data pertaining to demographics, history, and SNOT-22 questionnaire domains were compared via univariate analysis as well as logistic regression with backwards variable selection. RESULTS: A total of 296 patients met inclusion criteria, of which 128 had NRFP and 168 had sinusitis. A significantly greater percentage of patients in the NRFP group were women of childbearing age (40.6% vs 28.0%, P = .02). Backwards variable selection resulted in a model with four variables predicting a diagnosis of NRFP-female sex (odds ratio [OR] = 2.998, P < .0001), no history of prior sinonasal surgery (OR = 0.340 for history vs no history, P < .01), low nasal domain score (OR = 0.551, P < .0001), and high ear/facial domain score (OR = 1.453, P < .01). CONCLUSION: Accurately identifying patients with NRFP at initial presentation based on history would help direct patients to the appropriate care pathway and prevent ineffective treatments such as antibiotics and sinus procedures. Our findings suggest that the suspicion for NRFP should be higher in women of child-bearing age as well as patients with greater ear/facial symptoms or lesser nasal symptoms.

Barosinusitis due to routine weather changes: A cross-sectional analysis of public websites.

Background: Sinusitis is a common diagnosis that can be erroneously associated with routine weather-related barometric pressure changes. In actuality, these pressure changes likely exacerbate migraine headaches, which can cause facial pain and pressure rather than true sinus inflammation. Objective: The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the Internet. Methods: An Internet search for relevant terms was conducted, and content of the resulting pages was assessed for associations between weather-related pressure changes and either sinusitis or migraine. Variations in reported results across different subtypes of Internet sources were analyzed. The primary outcomes measured were (1) whether a given media source associated barometric weather changes with sinusitis, (2) whether that source associated barometric weather changes with migraine, and (3) treatment options offered by that source. Results: Of the 116 included webpages, 36 (31.03%) associated sinusitis and routine barometric pressure changes. Of these, 10 (27.77%) were otolaryngology practice sites. Sixty-seven webpages (57.76%) associated migraine and routine barometric pressure changes. Of these, nonotolaryngology webpages were more likely to report this link. Conclusions: Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with sinusitis. Nonotolaryngology sources were more likely to link weather-related pressure changes to migraine. These results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

Safety and Feasibility of Steroid-Eluting Stent as a Bolster in Endoscopic Anterior Skull Base Reconstruction.

BACKGROUND: With a rising incidence of cerebrospinal fluid (CSF) leaks, endoscopic endonasal CSF leak repair is increasingly performed. Current approaches utilize a variety of materials including free mucosal grafts and vascularized flaps, but post-op leaks continue to be reported. Steroid-eluting bioabsorbable stents (SES) are used during functional endoscopic sinus surgery for chronic rhinosinusitis to reduce inflammation and scarring while maintaining patency of sinus ostia. OBJECTIVE: The aim of this study is to assess the feasibility of SES as a graft/flap bolster for endoscopic endonasal CSF leak repair. METHODS: This is a retrospective review of patients undergoing endoscopic endonasal CSF leak repair with SES placed as part of the bolster technique at a tertiary care center between January 2019 and May 2022. Age, sex, BMI, comorbid idiopathic intracranial hypertension, pathology, location of CSF leak, intraoperative CSF leak flow, reconstruction type, and presence of post-op CSF leak were recorded. RESULTS: Twelve patients (mean age 52, median BMI 30.9, 58% female) had SES placement as part of the bolster technique. The most common pathology was meningoencephalocele (75%). Reconstruction was performed with either a free mucosal graft (6), or a flap (6). No post-op CSF leaks occurred at a reconstruction site with a stent, and no known complications were reported. All sinusotomies were patent at the last follow-up visit. CONCLUSIONS: SES placement as an adjunct to graft and/or flap bolster appears to be safe and feasible during anterior skull base reconstruction and CSF leak repair providing longer term structural support and preserving sinus drainage patency.

Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.

The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1+ immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3+ microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.

Epidemiologic factors and surgical outcomes in patients with nasal polyposis and asthma.

BACKGROUND/AIM: To evaluate the role of epidemiologic factors in surgical outcomes for patients with nasal polyposis (NP) and asthma. METHODS: Data was prospectively collected on patients who underwent endoscopic sinus surgery over a 7-year period. Among patients with chronic rhinosinusitis (CRS) with NP and asthma, surgical outcomes were analyzed according to gender and race. RESULTS: Patients with NP and asthma had significantly higher Lund-Kennedy and SNOT-20 scores--pre- and postoperatively--compared to CRS patients without NP or asthma. Both Caucasians and African-Americans in the CRS with NP/asthma group showed a statistically significant improvement at 6 months. Caucasians continued to have a significant improvement at 12 months, whereas African-Americans did not. There were no differences according to gender. CONCLUSION: In our patient population, African-Americans with NP and asthma had poorer outcomes following functional endoscopic sinus surgery.

Immunoglobulin Deficiency and the Unified Airway.

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.

Use of Tympanostomy T-Tube for Endoscopic Endonasal Marsupialization of Small Rathke's Cleft Cysts: A Case Series.

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.

Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of 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 ∼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 ∼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. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.

Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

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 < .001) and was more likely to designate this symptom as most important (P < .001). The CRSsNP group scored significantly higher in nasal blockage (P < .001), thick nasal discharge (P < .001), facial pain/pressure (P < .001), and in the ear/facial (P < .001) and rhinologic (P = .003) domains. Multivariable logistic regression revealed that runny nose (P < .001) was most predictive of spontaneous CSF rhinorrhea while nasal blockage (P < .001), thick nasal discharge (P < .001), and facial pain/pressure (P = .001) were predictive of CRSsNP after adjusting for relevant confounders. No significant difference was observed in total SNOT-22 scores between groups (P = .676). 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.

SNOT-22 Quality of Life Scores Improve After Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Rhinorrhea.

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 < .001), postnasal discharge (P < .001), wake up at night (P = .024), and embarrassed (P = .002). The CRSsNP group improved more in sneezing (P = .027), nasal blockage (P < .001), decreased sense of smell/taste (P = .011), thick nasal discharge (P < .001), facial pain/pressure (P = .008), and the ear/facial domain (P = .010). 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.

Nasal Cavity Squamous Cell Carcinoma: Factors Associated With Treatment Outcomes and Potential Organ Preservation.

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 < .001). In early stage NCSCC (T1/T2, N0), there was no significant difference in OS between patients treated with surgery only or surgery with adjuvant RT compared to definitive RT. In advanced stage NCSCC, surgery with adjuvant RT had a better OS compared to definitive chemoradiation. Having positive margins was shown to predict a worse OS when compared to negative margins in surgical patients despite adjuvant RT or chemoradiation. 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.

Characterizing Olfactory Dysfunction in Patients with Unilateral Cleft Lip Nasal Deformities.

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.

Sinus headache: changing the treatment paradigm.

PURPOSE OF REVIEW: 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 FINDINGS: 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. SUMMARY: 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.

Management of Chronic Rhinosinusitis Prior to Otolaryngology Referral: An Opportunity for Quality Improvement.

OBJECTIVE: 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. STUDY DESIGN: Retrospective review of a national claims database. SETTING: Academic institution. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Endoscopic Sinus Surgery in Older Patients With Significant Medical Comorbidities.

BACKGROUND: Endoscopic sinus surgery (ESS) offers excellent outcomes for patients with chronic rhinosinusitis (CRS) in the general population. It is unclear whether older patients with significant medical comorbidities experience similar benefits. OBJECTIVE: The purpose of this study is to evaluate whether increasing medical comorbidity is associated with worse sinonasal quality of life outcomes after ESS in older patients. METHODS: This is a retrospective study of CRS patients 55 years or older who underwent elective ESS at an academic institution from July 2017 to June 2019. 22-Item Sino-Nasal Outcomes Test (SNOT-22) scores were gathered at baseline as well as at 3 and 6 months following surgery. Data on demographics, medical comorbidities, preoperative Lund-Mackay (LM) scores, and postoperative complications were extracted from the medical record. The Charlson Comorbidity Index (CCI) was calculated for each patient. Multivariate linear regression was used to evaluate a potential association between CCI and change in SNOT-22 scores at 3 months postoperatively. RESULTS: A total of 205 patients met inclusion criteria with a mean (SD) CCI score of 2 (2.4) and a CCI score range of 0 to 11. The mean (SD) LM score was 8 (5.3). Rates of asthma and nasal polyposis were 28.3% and 36.6%, respectively. The mean (SD) improvement in SNOT-22 scores at 3 and 6 months compared to baseline was 17.9 (19.7) and 20.9 (18.1) points, respectively. After adjusting for covariates, there was no significant association between CCI and change in SNOT-22 scores. CONCLUSION: Greater medical comorbidity is not associated with worse SNOT-22 outcomes postoperatively, although future studies are needed to determine if comorbidities are associated with higher complication rates. A multidisciplinary approach to perioperative care is critical in maintaining the safety and efficacy of ESS in this patient population.

Endoscopic Sinus Surgery for Cystic Fibrosis: Variables Influencing Sinonasal and Pulmonary Outcomes.

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 < .001). Pseudomonas on culture was associated with less improvement in sinonasal scores (P = .002). There was no significant change in forced expiratory volume after surgery (P = .94). Revision surgery (P = .004) and older age (P = .007) were associated with less favorable change of pulmonary function on stepwise regression (P = .002). There was no correlation between change in sinonasal scores and pulmonary function. 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.

Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans.

BACKGROUNDPresbyosmia, 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) is the peripheral organ for olfaction and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult 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.MethodsAccordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single-cell RNA-Sequencing (scRNA-Seq), and culture studies.ResultsWe 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. Using a culture model, we found that cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation.ConclusionsOur data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction.FundingNIH grants DC018371, NS121067, DC016224; Office of Physician-Scientist Development, Burroughs-Wellcome Fund Research Fellowship for Medical Students Award, Duke University School of Medicine.