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OBJECTIVES Oral corticosteroid (OCS) as a part of appropriate medical therapy (AMT) (formerly maximal medical therapy) in chronic rhinosinusitis remains controversial. While the risks of OCS are well known, the benefit remains unclear due the absence of a standardized prescribing regimen. Consequently, it is difficult to characterize whether the risks of OCS and its ability to avert endoscopic sinus surgery (ESS) are helpful in AMT. When OCS is highly effective at averting surgery, the lesser risks of OCS would be justified because it can avoid the greater risks of ESS. When OCS is poorly effective at averting ESS, the risks of OCS would not be justified because many patients will be exposed to both risks. This study seeks to identify the threshold effectiveness of OCS at averting ESS that would minimize risk exposure to patients. METHODS A probabilistic risks-based decision analysis was constructed from literature reported incidences and impacts of adverse events of OCS and ESS. Monte Carlo analysis was performed to identify the minimum effectiveness required to avoid further intervention (MERAFI) for chronic sinusitis without nasal polyp (CRSsNP) and chronic sinusitis with nasal polyp (CRSwNP). RESULTS The analysis showed MERAFI results of 20.8% (95% CI 20.7-20.9%) for CRSsNP and 16.8% (95% CI 16.7-16.9%) for CRSwNP. CONCLUSIONS Given reported OCS effectiveness in the range of 34-71% in CRSsNP and 46-63% in CRSwNP, this analysis suggests that the inclusion of OCS in AMT may be the lower risk strategy. LEVEL OF EVIDENCE N/A Laryngoscope, 131:473-481, 2021.

OBJECTIVES Prior studies have indicated that olfactory cleft (OC) opacification correlates with olfaction in patients with chronic rhinosinusitis (CRS). However, the results have been unclear in patients without polyps. The purpose of this study was to further explore the relationship between OC opacification, sinus opacification, and olfactory function in patients with CRS. METHODS One hundred and forty-eight patients with CRS were prospectively enrolled across five institutions. Olfactory function was evaluated using the Sniffin' Sticks tests (Burghardt, Wedel, Germany) and the 17-item Questionnaire of Olfactory Disorders (QOD-NS). Computed tomography (CT) scans for each patient were acquired and Lund-Mackay scores recorded. Opacification of the OC was determined using OsiriX MD (Pixmeo, Bernex, Switzerland) and correlated with olfaction scores. RESULTS A total of 148 CRS patients, 73 CRS without nasal polyps (CRSsNP) and 75 CRS with nasal polyps (CRSwNP), as well as 30 control subjects were enrolled. Overall OC opacification averaged 63.7% in CRS patients and 47.1% in control subjects (P

OBJECTIVE To determine the impact of race and ethnicity on 30-day complications following pediatric endoscopic sinus surgery (ESS). STUDY DESIGN Cross-sectional cohort study. SUBJECTS AND METHODS Patients ≤ 18 years of age undergoing ESS from 2015 to 2017 were identified in the Pediatric National Surgical Improvement Program-Pediatric database. Patient demographics, comorbidities, surgical indication, and postoperative complications were extracted. Patient race/ethnicity included non-Hispanic black, non-Hispanic white, Hispanic, and other. Multivariable logistic regression was performed to determine if race/ethnicity was a predictor of postoperative complications after ESS. RESULTS A total of 4,337 patients were included in the study. The median age was 10.9 (interquartile range: 14.5-6.7) years. The cohort was comprised of 68.3% non-Hispanic white, 13.9% non-Hispanic black, 9.7% Hispanic, and 2.1% other. The 30-day complication rate was 3.2%, and the mortality rate was 0.3%. The rate of reoperation was 3.8%, and readmission was 4.1%. Black and Hispanic patients had higher rates of urgent operations (P = .003 and P

OBJECTIVES/HYPOTHESIS There is a growing need to understand the underlying mechanisms of age-related olfactory dysfunction with the increasing proportion of older adults over the next 20 years. Despite the importance of olfactory cleft (OC) volumes on odorant deposition and olfactory function, little is known about age-related changes to OC volume. The goal of this study was to use automated techniques in a cross-sectional design to investigate the extent to which OC volumes vary with age and determine the spatial specificity of any age-related effects. STUDY DESIGN Retrospective cross-sectional study. METHODS Deformation-based morphometry was utilized to measure OC and sinus volumes in two independent samples of 101 (Medical University of South Carolina [MUSC] sample) and 95 (Hammersmith sample) healthy adults who underwent T1-weighted magnetic resonance imaging, with the Hammersmith sample serving as a replication sample. RESULTS The mean age of the MUSC and Hammersmith samples were 54.9 ± 17.0 years and 52.1 years ± 15.7 years, respectively. In both samples, there was a significant positive association between age and OC volume that occurred at a constant rate across the lifespan (Cohen's f2 of 0.065 in the MUSC sample and 0.110 in the Hammersmith sample). Age-associated OC volume increases occurred in conjunction with decreases in sinus volumes as well as increases in non-OC nasal cavity volumes. CONCLUSIONS In this cross-sectional study, there is an increase in OC volume with increasing age that occurs in the context of broad age-associated differences in sinonasal anatomy. Future studies should investigate the impact of age-associated differences in intranasal anatomy on nasal airflow, odorant deposition, and olfactory function. LEVEL OF EVIDENCE 4 Laryngoscope, 129:E55-E60, 2019.

OBJECTIVE The goals of this study were to assess retronasal olfaction in patients with chronic rhinosinusitis (CRS) and describe clinical factors that influence retronasal olfaction. This study sought to investigate the influence of retronasal olfaction on patient-perceived outcomes and examine the relationship between retronasal and orthonasal olfaction. METHODS Retronasal olfactory function was tested using odorized powders in the oral cavity, whereas Sniffin' Sticks test (Burghart Instruments, Wedel, Germany) were used to assess orthonasal function prospectively in 69 adult CRS patients. Endoscopic evaluation of the olfactory cleft was scored using the Olfactory Cleft Endoscopy Scale (OCES). Several quality-of-life (QOL) instruments relating to sinonasal, olfactory, and chemosensory functions were used to assess the interactions between patient-reported outcome measures and retronasal olfaction. RESULTS There was strong correlation between retronasal and total orthonasal olfaction scores (r = 0.77, P

OBJECTIVES/HYPOTHESIS The goal of the study was to perform a systematic review with meta-analysis to determine the mean change in the 22-item Sino-Nasal Outcome Test (SNOT-22) across patients who have had endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) in the literature. METHODS A literature search was performed to identify studies that assessed SNOT-22 scores before and after ESS in adult patients with CRS. A random effects model with inverse variance weighting was used to generate the mean change after surgery, along with the forest plot and 95% confidence interval (CI). The impact of patient-specific factors across studies was assessed using a mixed-effects meta-regression. RESULTS The final study list included 40 unique patient cohorts published from 2008 to 2016. All studies showed a statistically significant change in mean SNOT-22 scores between baseline and postoperative time points (P < .001), ranging from 12.7 to 44.8, at an average follow-up of 10.6 months. The summary change in mean SNOT-22 across all studies was 24.4 (95% CI: 22.0-26.8). After forward, step-wise multivariate modeling, studies with higher mean preoperative SNOT-22 score and higher asthma prevalence were associated with greater changes in SNOT-22 score after ESS, whereas studies with longer mean follow-up had smaller changes in SNOT-22 score. CONCLUSIONS Studies evaluating quality-of-life outcomes after sinus surgery using the SNOT-22 instrument universally show significant improvement after ESS. Across the published literature, the magnitude of change is quite variable and appears to be influenced by a number of factors including baseline SNOT-22 score, asthma prevalence, and length of follow-up. Laryngoscope, 128:581-592, 2018.

Objectives Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study were to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. Data Sources A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Review Methods Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. Results A total of 47 articles were included in a systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin' Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96 ± 7.11 using the 40-item Smell Identification Test, 8.60 ± 2.81 using the Brief Smell Identification Test, 21.96 ± 8.88 using total Sniffin' Sticks score, 5.65 ± 1.51 using Sniffin' Sticks–Threshold, 9.21 ± 4.63 using Sniffin' Sticks–Discrimination, 9.47 ± 3.92 using Sniffin' Sticks–Identification, and 8.90 ± 5.14 using the Questionnaire for Olfactory Disorders–Negative Statements. Conclusions In CRS populations, a significant percentage of patients experience olfactory dysfunction, and mean olfactory scores are within the dysosmic range. Laryngoscope, 2016 127:309–320, 2017

Objectives/Hypothesis The objective of this investigation was to evaluate endoscopic sinus surgery (ESS) outcomes for chronic rhinosinusitis (CRS) between medical centers to determine if differences in quality-of-life outcomes were detectable. In addition, we sought to identify significant, independent cofactors toward the development of an ESS-specific risk-adjustment model so that ESS outcomes may be appropriately compared between institutions and healthcare providers. Study Design Prospective, multicenter, observational cohort. Methods Study participants electing ESS for CRS were enrolled and randomly selected in equal numbers from three academic clinical practices in North America between April 2011 and May 2015. The magnitude of average 6-month postoperative improvement in patient-related outcome measures (PROMs) was compared between enrollment sites using multivariate linear regression modeling. Results A total of 228 participants met inclusion criteria and were included for final analyses (n = 76 per site). The prevalence of septal deviation/septoplasty and oral corticosteroid-dependent conditions was significantly different between enrollment sites (P ≤ 0.004). Each enrollment site generated significant within-subject improvement across all PROMs after ESS (P < 0.001); however, average unadjusted magnitudes of improvement were significantly different between sites for the primary outcome measure. After controlling for baseline PROMs, septal deviation, steroid-dependent conditions, and medication use variables, enrollment site was no longer associated with significant outcome differences (P = 0.535). Conclusion Comparison of surgeon outcomes of ESS is feasible and must take into account a number of baseline patient characteristics. Further studies will be critical toward developing an ESS-specific risk-adjustment model and enabling a robust comparison of surgeon outcomes. Level of Evidence 2c. Laryngoscope, 2016

OBJECTIVES: There is a growing need to understand the underlying mechanisms of age-related olfactory dysfunction with the increasing proportion of older adults over the next 20 years. Despite the importance of olfactory cleft (OC) volumes on odorant deposition and olfactory function, little is known about age-related changes OC volume. The goal of this study was to use automated techniques in a cross-sectional design to investigate the extent to which OC volumes vary with age and determine the spatial specificity of any age-related effects. METHODS: Deformation-based morphometry was utilized to measure OC and sinus volumes in two independent samples of 101 (MUSC sample) and 95 (Hammersmith sample) healthy adults who underwent T1-weighted magnetic resonance imaging, with the Hammersmith sample serving as a replication sample. RESULTS: The mean age of the MUSC and Hammersmith samples were 54.9 ± 17.0 years and 52.1 years ± 15.7 years, respectively. In both samples, there was a significant positive association between age and OC volume that occurred at a constant rate across the lifespan (Cohen’s f(2) of 0.065 in the MUSC sample and 0.110 in the Hammersmith sample). Age-associated OC volume increases occurred in conjunction with decreases in sinus volumes as well as increases in non-OC nasal cavity volumes. CONCLUSIONS: In this cross-sectional study, there is an increase in OC volume with increasing age that occurs in the context of broad age-associated differences in sinonasal anatomy. Future studies should investigate the impact of age-associated differences in intranasal anatomy on nasal airflow, odorant deposition, and olfactory function.

Objectives/Hypothesis The primary objective of this pilot study was to define the change in productivity costs following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Secondary objectives were to identify CRS-related characteristics that may influence the degree of productivity improvement after ESS. Study Design Prospective, multi-institutional, observational cohort study. Methods The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 US Census and the 2013 US Department of Labor statistics. Results Twenty-seven patients with refractory CRS who underwent ESS were followed for a mean of 15 months (range, 8–25 months). Following ESS, there were improvements in annual absenteeism (22 days reduced to 3 days), annual presenteeism (41 days reduced to 19 days), and annual household days lost (12 days reduced to 6 days). Overall, the preoperative productivity costs were reduced after ESS ($9,190 vs. $3,373, respectively; P < .001). Conclusions Daily productivity is negatively impacted by the presence of CRS. The outcomes from this study provide the first insights into the reduced productivity costs associated with receiving ESS for refractory CRS. Future studies with larger sample sizes will need to validate the results from this pilot study. Level of Evidence 2c Laryngoscope, 2015

Objectives/Hypothesis: The purpose of this study is to improve patient understanding of surgical outcomes while they make a preference-sensitive decision regarding electing endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Study Design: Prospective observational cohort study. Methods: Patients with CRS who elected ESS were prospectively enrolled into a multi-institutional, observational cohort study. Patients’ were categorized into 10 preoperative Sino-Nasal Outcome Test (SNOT-22) groups based on 10-point increments beginning with a score of 10 and ending at 110. The proportion of patients achieving a SNOT-22 minimal clinically important difference (MCID) (9 points) and the percentage of relative improvement (%) for each preoperative SNOT-22 group were calculated. A subgroup analysis based on polyp status was performed. Results: A total of 327 patients were included in this study. Patients with a SNOT-22 score between 10 and 19 had the lowest chance of achieving an MCID (37.5%) and received a relative mean worsening of their quality of life (QoL) after ESS (118.8%). Patients with a SNOT-22 score greater than 30 obtained a greater than 75% chance of achieving an MCID, and there was a relative improvement of 45% in QoL (all < 244.9%) after ESS. Outcomes from the polyp status subgroup analysis were similar to the findings from the overall cohort. Conclusion: Outcomes from this study suggest that patients with a preoperative SNOT-22 score higher than 30 points receive a greater than 75% chance of achieving an MCID and on average obtain a 45% relative improvement in their QoL after ESS. Patients with SNOT-22 score of less than 20 did not experience improved QoL from ESS.

Objectives/Hypothesis To evaluate the long-term cost-effectiveness of endoscopic sinus surgery (ESS) compared to continued medical therapy for patients with refractory chronic rhinosinusitis (CRS). Study Design Cohort-style Markov decision-tree economic evaluation. Methods The economic perspective was the U.S. third-party payer with a 30-year time horizon. The two comparative treatment strategies were: 1) ESS, followed by appropriate postoperative medical therapy; and 2) continued medical therapy alone. Primary outcome was the incremental cost per quality-adjusted life year (QALY). Costs were discounted at a rate of 3.5% in the reference case. Multiple sensitivity analyses were performed, including differing time-horizons, discounting scenarios, and a probabilistic sensitivity analysis (PSA). Results The reference case demonstrated that the ESS strategy cost a total of $48,838.38 and produced a total of 20.50 QALYs. The medical therapy alone strategy cost a total of $28,948.98 and produced a total of 17.13 QALYs. The incremental cost effectiveness ratio for ESS versus medical therapy alone is $5,901.90 per QALY. The cost-effectiveness acceptability curve from the PSA demonstrated that there is a 74% certainty that the ESS strategy is the most cost-effective decision for any willingness to pay a threshold greater than $25,000. The time-horizon analysis suggests that ESS becomes the cost-effective intervention within the third year after surgery. Conclusion Results from this study suggest that employing an ESS treatment strategy is the most cost-effective intervention compared to continued medical therapy alone for the long-term management of patients with refractory CRS. Level of Evidence N/A. Laryngoscope, 125:25–32, 2015

Objectives/Hypothesis Disease-specific reductions in patient productivity can lead to substantial economic losses to society. The purpose of this study was to: 1) define the annual productivity cost for a patient with refractory chronic rhinosinusitis (CRS) and 2) evaluate the relationship between degree of productivity cost and CRS-specific characteristics. Study Design Prospective, multi-institutional, observational cohort study. Methods The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time was quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 U.S. National Census and the 2013 U.S. Department of Labor statistics. Results A total of 55 patients with refractory CRS were enrolled. The mean work days lost related to absenteeism and presenteeism were 24.6 and 38.8 days per year, respectively. A total of 21.2 household days were lost per year related to daily sinus care requirements. The overall annual productivity cost was $10,077.07 per patient with refractory CRS. Productivity costs increased with worsening disease-specific QoL (r = 0.440; p = 0.001). Conclusion Results from this study have demonstrated that the annual productivity cost associated with refractory CRS is $10,077.07 per patient. This substantial cost to society provides a strong incentive to optimize current treatment protocols and continue evaluating novel clinical interventions to reduce this cost. Level of Evidence N/A. Laryngoscope, 124:2007–2012, 2014

Objectives/Hypothesis Synechiae are one of the most common unwanted outcomes after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). However, there has been scant investigation into the true significance of synechiae formation after ESS. The aim of this study was to evaluate the impact of synechiae formation on health-related quality of life (HRQoL) outcomes after ESS in patients with CRS. Study Design Prospective, multi-institutional cohort. Methods Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS) scores were measured in adult patients before and after undergoing ESS for CRS. Differences in HRQoL were evaluated between those who developed sinonasal synechiae and those who did not, controlling for demographic factors, medical comorbidities, and measures of disease severity at baseline. Results A total of 286 patients underwent ESS, with 55 (19.2%) developing synechiae in the follow-up period. Patients developing synechiae reported significantly less improvement on the RSDI total scores (13.5 vs. 21.4, P = 0.008), RSDI physical subscores (5.3 vs. 8.3, P = 0.007), RSDI emotional subscores (2.9 vs. 5.8, P = 0.008), CSS total scores (14.5 vs. 21.2, P = 0.093), and CSS symptom subscores (19.9 vs 30.3, P = 0.069) compared to those who did not develop synechiae postoperatively. These differences persisted even after controlling for baseline differences in disease severity. Conclusions Synechiae of the sinonasal cavity commonly occurs following ESS, particularly in those undergoing revision surgeries. Although both groups improve, the degree of HRQoL improvement appears to be less in those who form postoperative synechiae after surgery compared to those who do not. Level of Evidence 2c. Laryngoscope, 123:2615–2619, 2013

Objectives/Hypothesis: Topical steroid therapy is an important strategy in the management of chronic rhinosinusitis (CRS) with nasal polyposis. The objective of this study was to determine the impact of topical steroid therapy on nasal symptoms in patients with nasal polyposis. Study Design: Systematic review with meta-analysis using standardized methodology. Methods: Study inclusion criteria included: randomized, placebo controlled trials, nasal polyposis, and topical steroid therapy. Exclusion criteria included: failure to report at least one symptom-based outcome measure, concurrent use of systemic steroids, or mixed CRS cohorts (polyp and nonpolyp patients). Quantitative analysis was performed using a random effect model. The PRISMA guidelines for meta-analysis reporting were followed. Results: A total of 19 studies fulfilled eligibility. Seven studies were excluded from the meta-analysis due to significant heterogeneity in outcome reporting. A total of 12 studies were combined for quantitative analysis and demonstrated a pooled risk ratio of 1.72 (95% confidence interval, 1.41–2.09), indicating a significant improvement in nasal symptoms. All three topical steroid preparations (fluticasone, mometasone, and budesonide) resulted in symptom improvement. All seven studies excluded from the meta-analysis qualitatively confirmed the overall findings. Conclusions: Topical nasal steroid therapy improves nasal symptoms in CRS patients with nasal polyposis. Future studies will need to evaluate the impact on quality of life, preferably using validated disease-specific instruments.

Objectives/Hypothesis: The primary study goal was to measure health state utility values in patients with chronic rhinosinusitis (CRS) before and after undergoing endoscopic sinus surgery (ESS). A secondary goal was to assess the meaning of these values by comparing them with other chronic disease processes and currently available medical or surgical treatments. Study Design: Prospective, observational cohort study. Methods: Adults with CRS were enrolled after electing ESS and were observed for a 5-year period. Baseline demographic and medical comorbidities were recorded for each patient, as well as findings from computed tomography (CT), endoscopy, olfaction, and disease-specific quality of life scores. Utility values were derived using the Short-Form 6D (SF-6D) at baseline and again after surgery. Results: The mean SF-6D utility value for the baseline health state of all patients with CRS (n = 232) was 0.65 (95% confidence interval [CI]: 0.63-0.66). Baseline utility values correlated with disease-specific quality of life as measured by the Rhinosinusitis Disability Index (r = −0.660; P < .001), but not baseline CT, endoscopy, or olfactory scores. Follow-up utility values (≥6 months) after ESS improved by 0.087 (95% CI: 0.06-0.12; P < .001) in patients with no history of sinus surgery and 0.062 (95% CI: 0.04-0.09; P < .001) in those undergoing a revision procedure. Conclusions: Patients with CRS who failed medical therapy and elected to undergo ESS reported health state utility values that were significantly lower than the US population norm. Utility values showed improvement after ESS, which was statistically and clinically significant. These results provide the initial data necessary for formal cost-effectiveness analyses incorporating ESS.

Objectives/Hypothesis: Pedicled mucosal flaps are the preferred method of endoscopic skull base reconstruction. Vascularized coverage of the anterior and posterior frontal tables remains a challenge given the lack of large caliber vessels supplying the anterior septum. The objective of this study was to define a novel bipedicled anterior septal (BAS) flap that is hypothesized to be capable of providing reproducible coverage of these difficult areas. Study Design: Radioanatomic and cadaveric study. Methods: The flap outline was superimposed over nine midline sagittal computed tomography images. The pedicles are comprised of the septal branch of the superior labial artery and the nasopalatine artery. The flap length subtended the distance from the incisive canal to the sphenoid face at the level of the choanal arch. Radiometric analysis of the flap length to base ratio and anterior/posterior frontal table coverage were calculated. These projected values were confirmed in four cadaveric dissection specimens. Results: The mean flap length was 39.64 6 4.26 mm with a mean length:base ratio of 3.29 6 0.70 and a total surface area of 916.46 6 262.66 mm 2 . The flap was estimated to provide coverage of 100.316 21.34% of the frontal beak and 50.74 6 32.54% of the posterior frontal table. In all cadaveric specimens the flap extended beyond the superior aspect of the frontal beak and at least 50% of the posterior table. Conclusions: The BAS flap represents a novel septal mucosal flap based on two well-defined arterial inputs. This flap is capable of providing reliable vascularized coverage of the posterior frontal table and the frontal beak following frontal

Introduction: Surfactant protein (SP)-B is a hydrophobic protein secreted within pulmonary surfactant that facilitates the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increases alveolar stability. SP-B may also have anti-inflammatory properties. It is implicated in decreasing the pulmonary inflammatory response to bacterial lipopolysaccharide. However, the expression and function of SP-B in the sinonasal cavities has not been elucidated. Our objective was to detect the presence of SP-B, measure alterations in several forms of chronic rhinosinusitis (CRS), and localize cellular protein expression. Materials/Methods: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFRS), nonatopic CRS with nasal polyposis (NP), and cystic fibrosis (CF) and in healthy controls. SP-B mRNA was measured in CRS and control patients using quantitative polymerase chain reaction. Immunoblot analysis and immunolocalization of SP-B were also performed. Results: CF (n = 4) showed significantly increased levels of SP-B (169-fold) mRNA (P = .004) when compared with controls (n = 5). CRS with NP (n = 5) and AFRS (n = 7) also demonstrated elevated levels of SP- B (14-fold and 4-fold, respectively) when compared with the control group, although these were not statistically significant. Immunoblot analysis confirmed the presence of the translated product, and immunolocalization revealed expression in the epithelium and submucosal glandular elements. Conclusion: This is the first study to detect and characterize SP-B in human sinus mucosa. Furthermore, SP-B is significantly up-regulated in CF CRS.

Otolaryngologists have assumed a major role in the evaluation and management of anterior skull base defects that result in cerebrospinal fluid (CSF) leaks and meningoencephaloceles. To achieve the best possible results for patients with CSF leaks, a thorough understanding of the underlying pathophysiology and a critical analysis of management principles and treatment options is essential. Surgical and medical management of these patients is highly individualized and depends on a number of factors, including etiology, anatomic site, patient age, and underlying intracranial pressure. This review article will highlight the history, physiology, pathophysiology, diagnosis, surgical techniques, and postoperative care relevant to nasal CSF leaks and encephaloceles.

Objectives/Hypothesis: Multiple spontaneous nasal meningoencephaloceles in the same patient are rare lesions. Although many skull base defects occur after prior trauma or surgery, otolaryngologists must be aware of the potential for spontaneous encephaloceles. We present our experience with this unusual condition and discuss its pathophysiology and unique management issues. Study Design: Retrospective. Methods: Review of medical records, radiographic images, and cerebrospinal fluid pressures. Results: We identified 5 patients with multiple, simultaneous, spontaneous encephaloceles: 4 patients with 2 encephaloceles and 1 patient with 3 encephaloceles (11 in all). Locations of the 11 encephaloceles were sphenoid lateral recess (6), frontal sinus with supraorbital ethmoid extension (2), ethmoid roof (1), frontal sinus (1), and central sphenoid (1). Three patients had bilateral sphenoid lateral recess encephaloceles, accounting for all six in that location. All four patients with available radiographic studies demonstrated empty sella turcica. Surgical approaches included endoscopic transpterygoid approach to the lateral sphenoid recess (3), endoscopic approach to ethmoid and central sphenoid (3), and osteoplastic flap with frontal sinus obliteration (2). We had 100% success at latest endoscopic follow-up (mean period, 17 mo). Three patients had postoperative lumbar punctures with mean cerebrospinal fluid pressure of 28.3 cm water (range, 19-34 cm; normal range, 0-15 cm). Conclusions: Multiple spontaneous encephaloceles can be managed safely and successfully using endoscopic and extracranial approaches. A high index of suspicion for this diagnosis must be maintained, especially in patients with radiographic evidence of laterally pneumatized sphenoid sinuses or empty sella. Spontaneous encephaloceles and cerebrospinal fluid leaks represent a form of intracranial hypertension.

To evaluate the long-term cost-effectiveness of endoscopic sinus surgery (ESS) compared to continued medical therapy for patients with refractory chronic rhinosinusitis (CRS).Cohort-style Markov decision-tree economic evaluation.The economic perspective was the U.S. third-party payer with a 30-year time horizon. The two comparative treatment strategies were: 1) ESS, followed by appropriate postoperative medical therapy; and 2) continued medical therapy alone. Primary outcome was the incremental cost per quality-adjusted life year (QALY). Costs were discounted at a rate of 3.5% in the reference case. Multiple sensitivity analyses were performed, including differing time-horizons, discounting scenarios, and a probabilistic sensitivity analysis (PSA).The reference case demonstrated that the ESS strategy cost a total of $48,838.38 and produced a total of 20.50 QALYs. The medical therapy alone strategy cost a total of $28,948.98 and produced a total of 17.13 QALYs. The incremental cost effectiveness ratio for ESS versus medical therapy alone is $5,901.90 per QALY. The cost-effectiveness acceptability curve from the PSA demonstrated that there is a 74% certainty that the ESS strategy is the most cost-effective decision for any willingness to pay a threshold greater than $25,000. The time-horizon analysis suggests that ESS becomes the cost-effective intervention within the third year after surgery.Results from this study suggest that employing an ESS treatment strategy is the most cost-effective intervention compared to continued medical therapy alone for the long-term management of patients with refractory CRS.

Objectives/Hypothesis Pain is a major cause of morbidity after tonsillectomy. Although various efforts have been made to reduce pain, the use of oral analgesics, which can have adverse side effects, remains the standard of care. It is hypothesized that fibrin sealant, used to achieve hemostasis and enhance healing in many surgical procedures, might help decrease pain after this operation. Study Design A prospective, randomized, blinded study was performed on 20 children aged 5 to 17 years who were undergoing tonsillectomy, to evaluate the efficacy of FIBRIN SEALANT in reducing postoperative pain. Methods All patients pre-donated 40 mL of blood from which autologous concentrated fibrinogen was prepared by cryoprecipitation. In the fibrin sealant group, fibrinogen and topical bovine thrombin were sprayed onto the surgical site to form fibrin sealant at the conclusion of tonsillectomy. The 10 patients in the control group (C) received no fibrin sealant. Patients rated their level of pain immediately after surgery and at regular intervals for 3 days after surgery using the Wong-Baker Faces Pain Rating Scale (1–6). Emesis, postoperative bleeding, medications, and adverse events were also evaluated. Results At 7:00 p.m. on postoperative day (POD) 0, the mean ± SD fibrin sealant group pain score (2.9 ± 0.41 units) was significantly lower than for the C group (4.1 ± 0.43 units;P ≤ .05). There was also a trend in favor of less pain in the fibrin sealant group at 7:00 p.m. on POD 1, with a mean of 3.5 ± 0.43 units versus 2.4 ± 0.48 units for C (P = .15). The odds of a patient in C experiencing emesis were 8.16 times higher, (P ≤ .05) than for patients in the fibrin sealant group. Conclusions Fibrin sealant significantly reduced pain the evening after pediatric tonsillectomy and also decreased the chance of e-periencing emesis. Thus fibrin sealant may be clinically useful as an adjunct to tonsillectomy.

Disease-specific reductions in patient productivity can lead to substantial economic losses to society. The purpose of this study was to: 1) define the annual productivity cost for a patient with refractory chronic rhinosinusitis (CRS) and 2) evaluate the relationship between degree of productivity cost and CRS-specific characteristics.Prospective, multi-institutional, observational cohort study.The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time was quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 U.S. National Census and the 2013 U.S. Department of Labor statistics.A total of 55 patients with refractory CRS were enrolled. The mean work days lost related to absenteeism and presenteeism were 24.6 and 38.8 days per year, respectively. A total of 21.2 household days were lost per year related to daily sinus care requirements. The overall annual productivity cost was $10,077.07 per patient with refractory CRS. Productivity costs increased with worsening disease-specific QoL (r = 0.440; p = 0.001).Results from this study have demonstrated that the annual productivity cost associated with refractory CRS is $10,077.07 per patient. This substantial cost to society provides a strong incentive to optimize current treatment protocols and continue evaluating novel clinical interventions to reduce this cost.

Objectives/Hypothesis: Compare cytokine levels in sinus tissue to sinus secretions from controls and chronic rhinosinusitis patients. Study Design: In vitro. Methods: Polyurethane foam sponges were placed into middle meati of patients with chronic rhinosinusitis without nasal polyps (CRSsNP), with polyps (CRSwNP), and controls. Sinus biopsies were then taken from the same location. Protein levels of tumor necrosis factor-alpha (TNF-a), interferon-c (IFN-c), and interleukins (IL) 2, 4, 6, 8, 10, and 17A were measured via cytometric bead assay for each sample. Protein values from sinus tissue and secretions were compared with Pearson’s correlation between samples as well as one-way ANOVA with posthoc t test between groups. Results: Samples from 43 patients in total were examined. Mucus was measured from 10 controls, 11 CRSsNP and 10 CRSwNP, and sinus tissue was measured from 10 controls, 15 CRSsNP and 10 CRSwNP. IL-8 and IFN-c levels were outside of the detectable range of the assay. Levels of secreted IL-2, 4, 6, 10, and 17A correlated with tissue levels (P 0.49) while TNF-a did not (P 5 0.71). CRSsNP had elevated mucus levels of IL-2, 4, 6, 10, and 17A compared to controls. CRSwNP had elevated mucus levels of IL-4, 6, 10, 17A, and TNF-a compared to controls. Conclusions: Cytokine levels in sinus secretions correlate with levels in sinus tissue and are elevated in CRS versus control based on Th1/Th2 skewing.

The primary study goal was to measure health state utility values in patients with chronic rhinosinusitis (CRS) before and after undergoing endoscopic sinus surgery (ESS). A secondary goal was to assess the meaning of these values by comparing them with other chronic disease processes and currently available medical or surgical treatments.Prospective, observational cohort study.Adults with CRS were enrolled after electing ESS and were observed for a 5-year period. Baseline demographic and medical comorbidities were recorded for each patient, as well as findings from computed tomography (CT), endoscopy, olfaction, and disease-specific quality of life scores. Utility values were derived using the Short-Form 6D (SF-6D) at baseline and again after surgery.The mean SF-6D utility value for the baseline health state of all patients with CRS (n = 232) was 0.65 (95% confidence interval [CI]: 0.63-0.66). Baseline utility values correlated with disease-specific quality of life as measured by the Rhinosinusitis Disability Index (r = -0.660; P.001), but not baseline CT, endoscopy, or olfactory scores. Follow-up utility values (≥ 6 months) after ESS improved by 0.087 (95% CI: 0.06-0.12; P.001) in patients with no history of sinus surgery and 0.062 (95% CI: 0.04-0.09; P.001) in those undergoing a revision procedure.Patients with CRS who failed medical therapy and elected to undergo ESS reported health state utility values that were significantly lower than the US population norm. Utility values showed improvement after ESS, which was statistically and clinically significant. These results provide the initial data necessary for formal cost-effectiveness analyses incorporating ESS.

Objectives: To review frontal sinus complications following frontal craniotomy and to describe management strategies. Study Design: Retrospective review. Methods: Retrospective review was made of six patients who had undergone frontal craniotomy and subsequently developed frontal sinus complications. Demographic data, indication for craniotomy, type of reconstruction, average time to development of complications, presenting symptoms, diagnosis, surgical management, follow-up, and outcomes were reported. Results: Complications included unilateral frontal sinus mucoceles in four patients, bilateral frontal sinus mucoceles in one patient, and bilateral frontal sinus mucopyoceles with upper-eyelid abscess in one patient. The average time to presentation of symptoms and development of complications following frontal craniotomy was 14.8 years (range, 1–39 y). Headaches were the most common presenting complaint. All patients underwent endoscopic mucocele marsupialization as part of their management. After an average follow-up period of 9 months, no recurrences were found and no complications occurred. Conclusion: A small number of patients develop otolaryngological complications, most commonly, frontal mucoceles, following frontal craniotomy. A high level of suspicion and long-term surveillance are needed to monitor for their occurrence. Endoscopic marsupialization may provide an effective, safe means for management.

Objectives/Hypothesis: Management of frontal sinus disease may require drill-out of bone in the frontal recess for access, ventilation, and drainage of the sinus cavity; removal of osteitic foci; or resection of neoplastic tissue. Technological advances, particularly burrs with angles of 70 degrees and stereotactic navigational imaging, offer new opportunities to provide access and minimize trauma. The preliminary study evaluates the safety and efficacy of such minimally invasive approaches. Study Design: Retrospective review. Methods: The authors describe the use of a 70-degree diamond burr in a series of 10 patients with complicated frontal sinus disease who underwent endoscopic frontal sinusotomy under stereotactic imaging guidance. Results: The diagnoses consisted of frontal sinus mucocele (n = 4), chronic frontal sinusitis (n = 1), Pott's puffy tumor after frontoethmoid fracture (n = 1), and recurrent inverting papilloma (n = 4). Partial septectomy was required in 6 of 10 patients. No complications were attributable to the drill-out procedure, despite a pre-existing fronto-ethmoid bony dehiscence in 6 of 10 patients. One patient had a CSF leak during removal of tumor from the skull base. One patient required revision frontal sinusotomy 10 months after the initial procedure, and another required further surgery for residual inverting papilloma on the medial orbital wall. All frontal sinusotomies were patent at last follow-up (mean period, 9.3 mo). Conclusion: Extended endoscopic frontal sinusotomy may be necessary in the management of complicated frontal sinus inflammatory disease and inverting papilloma. The 70-degree diamond burr is a safe and effective tool for access to the frontal recess. Complication rates appear to be similar to those for other extended frontal sinusotomy approaches.

Objectives: To determine bacterial and fungal organisms that are present in patients undergoing surgery for chronic frontal sinusitis. Study Design: Retrospective, nonrandomized study. Methods: Retrospective, nonrandomized bacterial and fungal cultures were performed on 46 sinus aspirates obtained by frontal sinus trephination performed on 30 consecutive patients with chronic frontal sinusitis. Results: Six patients were having sinus surgery for the first time, 19 patients had undergone prior functional endoscopic sinus surgery without instrumentation of the frontal sinus/recess, and the third group included 5 patients who had undergone prior frontal sinus/ recess surgery. Preoperative computed tomography scan of the frontal sinuses revealed complete opacification in 63% (29/46 frontal sinuses) and partial opacification in 22% (10/46), and no data were available for 15% (7/46). Aerobic cultures revealed that 38% (13/35 cultures) had no growth, 21% (7/35) grew Staphylococcus aureus, 21% (7/35) grew coagulase-negative Staphylococcus, 9% (3/35) grew Haemophilus influenzae, and 26% (9/35) grew a variety of other organisms. Anaerobic cultures were positive in 3% (1/32) of sinuses, and fungal cultures were positive in 4% (1/24). Haemophilus influenzae was most common in primary cases, whereas coagulase-negative Staphylococcus was most common in patients undergoing revision frontal sinus surgery. There were no other significant differences between cultures from patients undergoing revision frontal sinus surgery, revision functional endoscopic sinus surgery without prior frontal surgery, and primary surgery. Conclusions: This study suggests that organisms involved in chronic inflammatory disease of the frontal sinus may change after previous sinus surgery. The study failed to support a significant role for anaerobes. The role for coagulase-negative Staphylococcus as a potential pathogen or a contaminating agent remains unclear.

Objectiue: Osseous defects of the head and neck are a common challenge for the otolaryngologist. To develop improved reconstructive options, osteoconductive engineering experiments are being conducted. A nasal critical-size defect (CSD) model has previously been described in which less than 7% bone healing is observed over 6 months. An implant containing fibrin sealant with and without osteoprogenitor cells is evaluated in this model. Study Design: Randomized controlled trial using a rodent model. Methods: A nasal CSD was Surgically created in 18 male retired breeder Sprague-Dawley rats. Six animals were not implanted with any material, six received fibrin sealant consisting of fibrin (26 mg/rnL) and thrombin (lo00 WmL), and six were implanted with fibrin sealant and rat calvarial osteoprogenitor cells (1.8 x 10‘ cell&&). Thirty days later, the animals were examined at necropsy by planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. Results: A thin layer of bone covered the defect in all of the treated animals. A statistically significant increase in bone density (P < .06) between fibrin sealant plus osteoprogenitor cells and each of the other groups was shown using radiodensitometric analysis. Histological analysis also confirmed this Merence. Concluswn: Osteoprogenitor cells contained within fibrin sealant result in a greater augmentation of bone regeneration than controls or fibrin sealant alone. Key Words: Critical-size defect, fibrin sealant, bone regeneration, nasal reconstruction, tissue engineering.