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The association of gustatory dysfunction (GD) with quality of life (QOL) and cognition in older adults is understudied. Our objective was to study the prevalence of GD in the community and explore impacts and associated factors.A prospective, multi-institutional, pre-COVID cohort of adults aged 50 and older had smell and taste testing using "Sniffin' Sticks" (TDI) and "Taste Strips". The impact of GD on mood, QOL, and social interaction was assessed through visual analog scales. Subjects completed the Questionnaire of Olfactory Disorders, Patient Health Questionnaire 9, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and the DeJong scale of loneliness.48 patients, average age of 54.7 years, were enrolled. 32% experienced GD on taste strips, and 62% experienced olfactory dysfunction (OD) on TDI. 29.5% had both GD and OD. GD and OD correlated with worsened cognitive function on MMSE (r = 0.392; 0.05, p = 0.018; 0.003). Subjects with both GD and OD had worse MMSE than either alone (p = 0.003). Dry mouth and difficult chewing correlated with GD (r = -0.37 and -0.31, p = 0.10 and 0.37). Self-reported GD and OD were correlated (r = 0.46, p = 0.001), as were psychophysical GD and OD (r = 0.394, p = 0.008). GD did not correlate with other metrics.32% of subjects experienced GD on psychophysical testing, yet most are unaware without impacts on daily life. However, GD correlates with worsened cognitive function. Taste testing may play a role in screening of neurocognitive decline, and multi-sensory dysfunction may indicate of worsened cognitive states. This article is protected by copyright. All rights reserved.

Background The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) is a 17-item instrument measuring olfactory-specific quality of life (QOL). However, in clinical research patients can be overwhelmed with multiple questionnaires. We recently developed the 7-item brief QOD-NS (B-QOD). Our objective was to evaluate the psychometric properties of the B-QOD in both the development (D) sample, and in a separate replication (R) sample. Methods Testing on D (n = 203) and R (n = 281) samples included initial exploratory factor analysis (EFA), followed by internal reliability, information loss, and confirmatory factor analysis (CFA). Finally, incremental predictive utility analysis (IPUA) was performed by correlating the B-QOD with the 22-item Sino-Nasal Outcome Test (SNOT-22) survey. Results EFAs of both D and R demonstrated an underlying single-factor structure (eigenvalue = 4.17 and 3.57, respectively) with comparable loading factors (R > 0.30 for both). B-QOD also had good internal reliability in both D and R (Cronbach's alpha = 0.88 and 0.83, respectively). Also, there is minimal information loss with B-QOD compared to QOD-NS in both D and R (R = 0.98 and 0.96, respectively). CFA indicates that the B-QOD single-factor model has good overall fit as measured by the Comparative Fit Index (CFI) and the Standardized Root Mean Squared Residuals (SRMSR) in the D and R samples (CFI = 0.99 and 0.97; SRMSR = 0.035 and 0.053). IPUA shows that the QOD-NS offers no additional predictive benefit of SNOT-22 scores when compared with B-QOD. Conclusion The 7-item B-QOD captures a structurally coherent and reliable single dimension, with minimal information loss and excellent external predictive utility when compared to the QOD-NS.

Background Many patients with chronic rhinosinusitis (CRS) have persistent olfactory dysfunction (OD) following endoscopic sinus surgery (ESS). Few studies compare outcomes to control subjects so it is unknown if residual OD is due to persistent CRS. Objective Compare postoperative measures of OD in case patients with CRS to healthy controls without sinonasal disease. Methods Prospective, observational, multicenter cohort study between October, 2016 and May, 2019. Case participants were selected from referred adult patients diagnosed with CRS, with or without nasal polyposis (NP), electing ESS as subsequent treatment modality. Controls voluntarily enrolled from a community-based sample without a history of CRS. Primary outcomes included measures of preoperative and postoperative OD using “Sniffin’ Stick” pens which summarize odorant threshold (T), discrimination (D), and identification (I) scores. Secondary outcomes included the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) survey and olfactory cleft endoscopy scores (OCES). Results Outcomes were compared between 113 cases and 164 controls of similar average age and gender. Cases reported significantly worse baseline Sniffin’ Sticks TDI total scores (−6.8[SE ± 1.0]; 95% CI: −4.9 to −8.7), QOD-NS (8.9[SE ± 1.1]; 95% CI: 6.8–10.9), and OCES (3.5[SE ± 0.4]; 95% CI: 2.9–4.2) on average. Cases reported significant postoperative improvement in TDI total score (3.7[SD ± 8.2]; 95% CI: 2.2–5.2), QOD-NS (−5.9[SD ± 8.7]; 95% CI: −7.6 to −4.3), and OCES (−1.7[SD ± 3.8]; 95% CI: −2.7 to −0.8) on average, while 63% of anosmics reported improved postoperative olfaction. Multivariate regression identified that NP (OR = 0.4; 95% CI: 0.2–1.0) and previous ESS (OR = 0.3; 95% CI: 0.1–0.8) decreased the odds of postoperative improvement equal to mean TDI scores of controls, while septoplasty increased those odds (OR = 4.5; 95% CI: 1.5–13.7). Conclusion ESS improved olfactory metrics and restored olfactory function in approximately 50% of patients with CRS to that of healthy controls. Concurrent septoplasty increased the likelihood of achieving normal olfaction, while NP and previous ESS decreased those odds.

Objective To investigate whether direct steroid application via Mygind's position improved objective and subjective measures of chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods A retrospective chart review was performed on patients seen by the senior author in a Rhinology Clinic of a tertiary academic center over a 2 year period. Patients whose only change in medical regimen was initiation of corticosteroid administration via Mygind's position were included for this analysis. The main subjective and objective outcome measures were Sino-nasal Outcome Test-22 (SNOT-22) and endoscopy scores, respectively. Patient scores before and after the change in treatment were compared and analyzed using Student's t test and Wilcoxon signed-rank test. Results Twenty-two patients were identified for inclusion. There was a statistically significant decrease in overall nasal endoscopy scores for both the right (P = .001) and left (P = .001) sides. A statistically significant and clinically meaningful decrease in total SNOT-22 scores (12.7 points, P = .008) was also seen. Intolerance to the regimen was observed in 5/48 patients reviewed for inclusion (10.4%), with issues including neck pain, burning, pressure, and thrush. Conclusion The direct application of topical corticosteroids, specifically via Mygind's position, may improve both objective exam findings and clinical symptomatology in patients with CRSwNP compared to indirect application. Intolerance to the regimen can be observed. Level of evidence 4-Case series (with or without comparison).

OBJECTIVES/HYPOTHESIS Statins have long been used in the management of cardiovascular disease for their lipid-lowering properties. However, recent research suggests that statins may also have anti-inflammatory effects via modulation of lipid-containing enzymes and mediators, and therefore may have therapeutic value in the treatment of chronic rhinosinusitis (CRS). STUDY DESIGN Retrospective database review. METHODS The 2006 to 2015 National Ambulatory Medical Care Survey (NAMCS) data were queried to analyze the relationship between statin use and rates of CRS. CRS was indicated by the presence of an International Classification of Diseases, Ninth Revision code for CRS in one of the five diagnosis variables. Statin use was indicated by the presence of a statin medication in any of the 30 medication variables using the Multum Lexicon Drug Database, with newly prescribed medications excluded. Relevant demographic, socioeconomic, and comorbid factors were included in a multivariate logistic regression model, which accounted for the complex, stratified, multistage survey design of the NAMCS. RESULTS There were 390,538 unweighted visit records used in the weighted analysis dataset, corresponding to 9,612,613,668 weighted visits. Statin use was associated with a decreased rate of CRS in both a univariate analysis (odds ratio [OR] = 0.53, P

Viral infections, especially those caused by rhinovirus, are the most common cause of asthma exacerbations. Previous studies have argued that impaired innate antiviral immunity and, as a consequence, more severe infections contribute to these exacerbations.These studies explored the innate immune response in the upper airway of volunteers with allergic rhinitis and asthma in comparison to healthy controls and interrogated how these differences corresponded to severity of infection.Volunteers with allergic rhinitis, those with asthma, and those who are healthy were inoculated with rhinovirus A16 and monitored for clinical symptoms. Tissue and nasal wash samples were evaluated for antiviral signature and viral load.Both subjects with allergic rhinitis and asthma were found to have more severe cold symptoms. Subjects with asthma had worsened asthma control and increased bronchial hyperreactivity in the setting of higher fractional exhaled breath nitric oxide and blood eosinophils. These studies confirmed reduced expression of interferons and virus-specific pattern recognition receptors in both cohorts with atopy. Nevertheless, despite this defect in innate immunity, volunteers with allergic rhinitis/asthma had reduced rhinovirus concentrations in comparison to the controls.These results confirm that the presence of an allergic inflammatory disorder of the airway is associated with reduced innate immune responsive to rhinovirus infection. Despite this, these volunteers with allergy have reduced viral loads, arguing for the presence of a compensatory mechanism to clear the infection.ClinicalTrials.gov Identifier: NCT02910401.

Background Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E2 (PGE2) production. Many cell types contribute to the disease; however, eosinophils are markedly elevated and are important drivers of pathologic findings. Objective To investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE2 to inhibit this activation. Methods Eosinophils were purified from blood of healthy individuals without AERD and stimulated with lysine aspirin, ketorolac, or sodium salicylate. The role of PGE2 in altering activation was determined by incubating eosinophils with increasing doses of PGE2 before lysine aspirin stimulation. Specific PGE2 receptor use was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLTs), leukotriene B4 (LTB4), and eosinophil-derived neurotoxin (EDN) were quantified by enzyme-linked immunosorbent assay. Results Stimulation of eosinophils with lysine aspirin, ketorolac, or sodium salicylate resulted in secretion of CysLTs and LTB4 in the absence of EDN release. Low doses of PGE2 inhibited LTB4 and CysLT release, an effect lost at higher PGE2 concentrations. Use of butaprost, an EP2 receptor agonist, suppressed lysine aspirin stimulation. This mechanism was supported by blocking activity of the EP1 and EP3 receptors. Conclusion Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB4. This effect can be inhibited by PGE2 acting through the EP2 receptor. The recognized loss of EP2 receptor expression combined with low PGE2 levels explains in part the sensitivity to NSAIDs.

Background Rhinovirus (RV) infections exacerbate asthma in part by enhancing an allergic state, and these exacerbations can be mitigated via administration of anti-IgE. Objective We investigated the presence of local IgE production in the nose of allergic and non-allergic subjects and assessed whether this was enhanced by RV. Methods Local production of specific IgE was determined by comparing ratios of specific to total IgE concentrations between nasal and serum samples. Our initial studies were performed in subjects presenting to the emergency department for allergic and non-allergic respiratory complaints. Subsequently, we investigated influences of experimental RV infection on nasal sIgE production in an allergic cohort. Results We found evidence of local sIgE production to Dermatophagoides pteronyssinus in 30.3% and to Blomia tropicalis in 14.6% of allergic subjects. None of the non-allergic subjects demonstrated local IgE. Subjects with active RV infection were more than twice as likely to have local sIgE (45% vs 14%), and subjects with local sIgE being produced were ~3 times more likely to be having an asthma exacerbation. Experimental RV infection was able to induce local sIgE production. Conclusion These studies confirm local IgE production in a large subset of allergic subjects and demonstrate that allergic asthmatics with local IgE are more likely to develop an asthma exacerbation when infected with RV. Our RV challenge studies demonstrate that at least some allergic asthmatics can be induced to secrete locally generated IgE in their nasal airway after RV infection.

Background The association between olfactory dysfunction (OD) and cognitive decline is becoming apparent in the emerging literature. However, the literature demonstrating a similar effect between gustatory dysfunction (GD) and cognition is not well established. Objective To determine whether OD and GD are independently associated with cognitive impairment. Methods The 2013–2014 National Health and Nutrition Examination Survey was queried for 1376 older adults, corresponding to a weighted population sample of 50 816 529, to assess olfactory and gustatory status and cognition using univariate and multivariate regression analyses. OD and GD were determined using objective measurements with validated protocols. Participants were stratified as normal or abnormal cognition status using accepted cutoff values as indicated for the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Results OD was associated with both mild cognitive impairment (odds ratio [OR] 1.809, P = .004) and dementia (OR 3.173, P Conclusions OD and severe GD represent independent predictors of cognitive impairment in a nationally representative sample of older adults.

BACKGROUND Giant pituitary macroadenomas with a diameter >4 cm are rare tumors, accounting for only about 5% of pituitary adenomas. They are more difficult to maximally resect safely owing to limited access as well as encasement of adjacent structures. Acidophil stem cell adenomas are rare immature neoplasms proposed to derive from common progenitor cells of somatotroph and lactotroph cells. These adenomas comprise about 4.3% of surgically removed pituitary adenomas. No previous reports have described acidophil stem cell adenomas that grow to the size of giant macroadenomas. This rare entity poses special challenges given the need for maximal safe resection in an immature neoplasm. OBSERVATIONS The authors report a 21-year-old female who presented with 3 years of progressive visual decline and a giant macroadenoma. She underwent endoscopic transsphenoidal surgery for decompression. Given the tumor size and involvement of adjacent critical structures, gross-total resection was not achieved. The authors review the literature on giant pituitary adenomas and provide a discussion on clinical management for this rare entity. LESSONS The authors present a very rare case of a giant pituitary adenoma of acidophil stem cell origin and discuss the technical and management challenges in this rare entity.

OBJECTIVES Urine leukotriene E4 (uLTE4) is a biomarker of leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P

Introduction Mood disorders frequently coexist with chronic rhinosinusitis (CRS), yet patient views of how mental health impacts their disease, and their willingness to engage in treatment is not well understood. Methods Subjects with CRS were enrolled regardless of their mental health status and completed a needs questionnaire on mental health as it related to CRS. In addition, demographic and disease-specific data were collected. Results We enrolled 55 subjects. In addition, 29.1% of them had polyps, with mean endoscopy/computed tomography (CT)/Sino-Nasal Outcome Test (SNOT-22) scores of 3.9/9.7/41.2, respectively and 45% thought depression was common in CRS patients. In total, 78.2% were open to taking a depression screener and would be comfortable discussing mental health with their Ear Nose and Throat provider, 76.4% of patients felt that treating mental health problems could improve sinus-related quality of life (QOL), and 87.3% were open to meeting with a mental health professional or participating in a course on managing stress/anxiety/mental health issues. The multivariate regression model of whether patients felt that treating the mind would improve sinus-related QOL as predicted by age, gender, SNOT-22, CT scores, and endoscopy scores was statistically significant ( P = .027) and explained 42% of the variance in answers, but only age and gender approached statistical significance ( P = .06 and .04). Conclusions CRS patients acknowledged the high prevalence of comorbid mood disorders and were willing to discuss and be treated for mental health issues. Many patients felt that treating their mental health would improve their disease-specific QOL. These findings warrant further study of how to incorporate the management of metal health into CRS treatment algorithms.

Hypertension has long been thought to influence the risk and severity of epistaxis. However, evaluation of the relevant literature reveals articles with methodologic concerns or limited quality. In many instances, these studies are not adequately controlled, and lack of multivariate analyses calls into question any noted association between epistaxis and hypertension. The goal of this commentary is to explain why there is limited guidance about the management of hypertension and the possible association with nosebleed in the 2020 American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guideline for nosebleeds. Background on the literature that describes the association between hypertension and nosebleeds is provided.

Objectives To characterize the association between quantitative olfactory dysfunction (OD) and gustatory dysfunction and depression in older adults. Methods The 2013–2014 National Health and Nutrition Examination Survey (NHANES) data were used to investigate the relationship between smell and taste dysfunction and depression. Adults aged 65 years and older were included in the analysis. For smell status, subjects were divided into hyposmia, anosmia, and OD (hyposmia + anosmia) using the Pocket Smell Test. For taste status, subjects were evaluated using quinine, 1M NaCl, and 0.32M NaCl solutions. Indicator variables were made for subjects with both smell and taste dysfunction to determine whether a combination of symptoms could predict depression. Depression status was evaluated by the 9-item Patient Health Questionnaire using accepted cutoff values. Relevant demographic, socioeconomic, and comorbid factors were included in multivariate logistic regression models, which accounted for the complex survey design of NHANES. Results A total of 931 subjects aged 65 years or older were included in the weighted analysis. Anosmia significantly predicted depressive symptoms in multivariate analysis (odds ratio [OR] = 2.484, P = .032) but not univariate. In univariate analysis, hyposmia + anosmia (OR = 2.193, P = .006) and hyposmia (OR = 2.512, P Conclusions Smell dysfunction is an independent predictor of depressive symptoms in a representative sample of older adults in the United States after adjusting for relevant demographic factors and comorbidities.

BACKGROUND Olfactory dysfunction (OD) in chronic rhinosinusitis (CRS) is common. It is likely that numerous factors such as sex, race, age, allergies, asthma, smoking, and other comorbidities play a role in CRS-related OD. In order to determine which aspects of OD are due solely to CRS and which are associated with other confounders, control populations are needed to allow appropriate risk assessments. METHODS Prospective, multi-institutional enrollment of patients with CRS and control subjects without CRS was performed. Demographic information, comorbidities, and olfactory testing (Sniffin' Sticks) of threshold (T), discrimination (D), and identification (I) scores (TDI) was collected. RESULTS A total of 224 patients with CRS and 164 control subjects were enrolled. Olfaction was worse in CRS patients compared to controls (mean ± standard deviation (SD) TDI = 22.4 ± 9.5 vs 28.8 ± 7.0, respectively, p < 0.001). Only 27% of CRS patients were normosmic compared to 49% of controls (p < 0.001). When stratifying by nasal polyp (NP) status, CRSwNP patients had significant impairments in TDI, T, D, and I compared to controls with mean differences of 11.2, 3.3, 3.5, and 4.4 points, respectively (all p < 0.001). In contrast, CRSsNP patients only had impaired T when compared to controls with a mean difference of 2.2 points (p < 0.001). Multivariate modeling of TDI scoring showed that OD was driven by polyps, asthma, diabetes, and age. CRSsNP was not independently associated with worse TDI scores. CONCLUSION OD in CRS patients is multifactorial. Independent drivers appear to be polyp status, asthma, diabetes, and age. OD in patients with CRSsNP is similar to controls with the exception of impaired thresholds.

The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients.The guideline development group made

Background Spontaneous cerebrospinal fluid (CSF) rhinorrhea has been associated with elevated intracranial pressure (ICP). As such, ICP reducing measures are commonly employed to optimize repair. Although postoperative acetazolamide use has been described, no data currently exists on the potential for preoperative use. Methods A retrospective review was performed including patients treated for anterior spontaneous CSF leaks by a single surgeon over a 6-year period during which acetazolamide therapy (250 mg twice daily) was employed before considering surgical repair. The primary endpoint was whether the patient went on to require surgical repair. Results A total of 16 patients were identified who were pretreated with acetazolamide. Leak sites were noted as cribriform (5/16), sphenoid (8/16), ethmoid (1/16), multiple (1/16), and indeterminate (1/16). Five patients had resolution of their rhinorrhea without surgery (31.3%). Mean follow-up for these nonsurgical patients was 470 days (range, 64 to 857 days). There were no differences in the patients' age or site of leak between surgical and nonsurgical patients (p = 0.65, p = 0.52, respectively). Nonsurgical patients had a lower body mass index (BMI) than surgical patients (p = 0.04). Conclusion This is the first study to report the use of acetazolamide therapy as a primary treatment option for spontaneous CSF rhinorrhea. This therapy enabled surgery to be avoided in 31.3% of patients. This would indicate that in the absence of other contraindications for delaying repair, a trial of acetazolamide therapy could be considered as an initial option in the management of isolated spontaneous CSF rhinorrhea.

Object The consistency of pituitary macroadenomas affects the complexity of surgical resection. On T2-weighted (T2W) imaging, the intensity ratio of the tumor to the cerebellar peduncle (tumor to cerebellar peduncle T2-weighted imaging intensity [TCTI] ratio) correlates with meningioma consistency. We aimed to determine the correlation of this radiographic finding with pituitary macroadenoma consistency and to determine whether it can be used for preoperative planning. Methods We performed a retrospective evaluation of 196 patients with macroadenomas who underwent endoscopic transsphenoidal resection from January 2012 to June 2017. Macroadenoma consistency was determined by one senior neurosurgeon at the time of surgery. Axial and coronal T2W magnetic resonance imaging images were evaluated retrospectively, and adenoma size, Knosp grade, suprasellar extension and TCTI were calculated. Results The mean TCTI ratio was 1.70 (95% confidence interval [CI]: 1.65–1.75). Intraoperatively, 140 (71.4%) adenomas were classified as soft and 48 (24.5%) as fibrous. Gross total resection was achieved in 66.7% of fibrous adenomas and in 86.4% of soft adenomas (p = 0.007). The mean ratio was 1.68 (95% CI: 1.62–1.74) for soft tumors and 1.76 (95%CI: 1.67–1.84) for fibrous tumors. There was no difference in the mean TCTI ratio between groups. Lactotroph and somatotroph adenomas had a lower mean TCTI ratio compared with other functioning and nonfunctioning adenomas with a mean TCTI of 1.52 compared with 1.77. Conclusions In this retrospective cohort study, we found that the TCTI ratio does not correlate with tumor consistency. We also noted that the TCTI ratio is increased in prolactin and growth hormone-secreting adenomas.

Background Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort. Methods Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin' Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification. Results Sixty-two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C-C motif ligand 2 (CCL2), interleukin-5 (IL-5), IL-6, IL-13, IL-10, IL-9, tumor necrosis factor-α (TNF-α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C-X-C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL-6, IL-10, vascular endothelial growth factor-A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund-Mackay score correlated only in the CRSsNP group (CXCL5, IL-5, IL-13, IgE). Conclusion Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.

Background Chronic rhinosinusitis is a difficult-to-treat disease that is often characterized by recurrent nasal polyp (NP) growth following surgical removal. The disease has been separated into distinct phenotypes based on cellular infiltrate or underlying physiological mechanisms. NPs are composed in part of an inflammatory cellular infiltrate, blood vessels, and a large amount of extracellular matrix (ECM). Despite the recognition of prominent ECM deposition, few studies have examined the components in detail and how they might differ with disease state. Objective The purpose of this study was to quantitate the expression of ECM components in NPs. Methods NPs were stained with pico-sirius red to determine total collagen content, and immunofluorescence was used to detect collagen I, collagen III, collagen IV, fibronectin, and laminin. Expression of each was quantitated and analyzed in relation to rhinosinusitis phenotype and separately as a function of polyp eosinophil number. Results When analyzed by phenotype, collagen I, collagen III, and fibronectin were expressed at the highest levels in noneosinophilic sinus disease. Collagen IV was not different among any groups, and its location was found predominately around vessels. When analyzed as a function of polyp eosinophil number, total collagen and collagen III showed a significant inverse correlation. Conclusions NP ECM composition differs with disease state with higher expression in cases where eosinophil levels are low. This suggests that in eosinophilic polyps there is a loss of matrix deposition either through break down or a failure to produce the essential components. Understanding these differences may identify new therapeutic targets.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to non-steroidal anti-inflammatory drugs (NSAID). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E2 (PGE2) production. Many cell types contribute to the disease, however eosinophils are markedly elevated and are important drivers of pathology. OBJECTIVE: Investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE2 to inhibit this activation. METHODS: Eosinophils were purified from blood of healthy non-AERD individuals and stimulated with lysine aspirin (LysASA), ketorolac or sodium salicylate. The role of PGE2 in altering activation was determined by incubating eosinophils with increasing doses of PGE2 prior to LysASA stimulation. Specific PGE2 receptor utilization was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLT), leukotriene B4 (LTB4) and eosinophil derived neurotoxin (EDN) were quantified by ELISA. RESULTS: Stimulation of eosinophils with LysASA, ketorolac or sodium salicylate resulted in secretion of CysLTs and LTB4 in the absence of EDN release. Low doses of PGE2 inhibited LTB4 and CysLT release; an effect lost at higher PGE2 concentrations. Use of butaprost, an EP2 receptor agonist, suppressed LysASA stimulation. This mechanism was supported by blocking activity of the EP1 and EP3 receptors. CONCLUSION: Eosinophils can be directly activated by NSAIDs via cyclooxygenase independent pathways to produce CysLTs and LTB4. This effect can be inhibited by PGE2 acting through the EP2 receptor. The recognized loss of EP2 receptor expression combined with low PGE2 levels, explain in part the sensitivity to NSAIDs.

Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of pro-inflammatory mediators including 5-lipoxygenase and leukotriene C4 synthase (LTC4S) that results in constitutive over-production of cysteinyl leukotrienes (CysLTs). Mast cells and eosinophils are two cell types that have important roles in mediating many of the effects observed in this disease. Increased levels of both interleukin (IL-4) and interferon (IFN)-γ are present in the tissue of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S by mast cells. Our studies demonstrate that IFN-γ, but not IL-4 drives this process in eosinophils. We also extend to both IL-4 and IFN-γ the ability to upregulate CysLT receptors. Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE2 concentrations are reduced in AERD and studies confirm that this reflects diminished expression of cyclooxygenase (COX)-2, a process again that is driven by IL-4. Thus, IL-4 and IFN-γ acting on eosinophils and mast cells together play an important pathogenic role in generating the phenotype of AERD. This review will examine the overall role that eosinophils and mast cells contribute to the pathophysiology of AERD.

Background T-helper (Th) type 2 cell inflammation is the hallmark of several disease processes, including asthma, atopic dermatitis, and some forms of chronic rhinosinusitis. Itraconazole has been used as both an antifungal and an anti-inflammatory agent, with some success in many of these diseases, in part, by altering Th2 cytokine expression by T cells. It is not known whether this merely reflects inhibition of established Th2-like cells or the inhibition of differentiation of naive T cells into Th2-like cells. Objective To evaluate the role of itraconazole in the differentiation of naive T cells during activation. Methods Naive CD45RA+ T cells were isolated from peripheral blood mononuclear cells from healthy volunteers. Th1 and Th2 type cells were differentiated in the presence of varying concentrations of itraconazole. After stimulation with anti-CD3 and anti-CD28 beads, carboxyfluorescein succinimidyl ester dilution was performed to evaluate proliferation and intracellular cytokine staining for interleukin (IL) 4 and interferon (IFN) gamma within proliferating T cells was measured along with enzyme-linked immunosorbent assay for secreted IL-5, IL-13, and IFN gamma. Results Itraconazole had no effect on proliferation of unbiased, Th1, or Th2 cells. Similarly, there was no effect of itraconazole on either intracellular cytokine staining of IL-4 and IFN gamma or secreted cytokine expression of IFN gamma, IL-5, and IL-13 in any of the cell populations. Conclusion Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.

OBJECT Both endoscopic and microscopic transsphenoidal approaches are accepted techniques for the resection of pituitary adenomas. Although studies have explored patient outcomes for each technique individually, none have prospectively compared sinonasal and quality of life outcomes in a concurrent series of patients at the same institution, as has been done in the present study. METHODS Patients with nonfunctioning adenomas undergoing transsphenoidal surgery were assessed for sinonasal function, quality of life, and pain using the Sino-Nasal Outcome Test-20 (SNOT-20), the short form of the Nasal Obstruction Symptom Evaluation (NOSE) instrument, the SF-36, and a headache scale. Eighty-two patients undergoing either endoscopic (47 patients) or microscopic (35 patients) surgery were surveyed preoperatively and at 24–48 hours, 2 weeks, 4 weeks, 8 weeks, and 1 year after surgery. RESULTS Patients who underwent endoscopic and microscopic transsphenoidal surgery experienced a similar recovery pattern, showing an initial increase in symptoms during the first 2 weeks, followed by a return to baseline by 4 weeks and improvement beyond baseline functioning by 8 weeks. Patients who underwent endoscopic surgery experienced better sinonasal outcomes at 24–48 hours (SNOT total p = 0.015, SNOT rhinologic subscale [ssRhino] p < 0.001), 2 weeks (NOSE p = 0.013), and 8 weeks (SNOT total p = 0.032 and SNOT ssRhino p = 0.035). By 1 year after surgery, no significant differences in sinonasal outcomes were observed between the 2 groups. Headache scales at 1 year improved in all dimensions except duration for both groups (total result 73%, p = 0.004; severity 46%, p < 0.001; frequency 53%, p < 0.001), with 80% of either microscopic or endoscopic patients experiencing improvement or resolution of headache symptoms. Endoscopic and microscopic patients experienced reduced vitality preoperatively compared with US population norms and remained low postoperatively. By 8 weeks after surgery, both groups experienced significant improvements in mental health (13%, p = 0.005) and vitality (15%, p = 0.037). By 1 year after surgery, patients improved significantly in mental health (14%, p = 0.03), role physical (14%, p = 0.036), social functioning (16%, p = 0.009), vitality (22%, p = 0.002), and SF-36 total (10%, p = 0.024) as compared with preoperative measures. There were no significant differences at any time point between the 2 groups for the total SF-36 or for any of the 8 subscales. CONCLUSIONS Patients who underwent either an endoscopic or a microscopic approach experienced the greatest nasal symptoms at 2 weeks postoperatively and exhibited similar time courses of recovery in nasal, headache, and quality of life assessments. Although patients who underwent endoscopic surgery experienced significantly fewer nasal symptoms during the first 8 weeks, by 1 year after surgery, there were no significant differences between the 2 groups.

Background Although previous studies of sinus surgery that used balloon catheter dilation technology for the paranasal sinuses (balloon sinus dilation [BSD]) demonstrated safety and efficacy, data that compare BSD with continued medical management (MM) are lacking. Objective To evaluate the outcomes of sinus surgery when using BSD instruments versus MM for patients with chronic rhinosinusitis for whom MM failed. Methods Adult patients with chronic rhinosinusitis for whom a minimum of 3 weeks of oral antibiotics, 4 weeks of daily saline solution therapy, and 4 weeks of daily nasal corticosteroids failed were included. Qualifying participants were allowed to self-select sinus surgery with BSD (either an office or operating room setting) or continued MM. The primary end point was the comparison of change in the Chronic Sinusitis Survey score from baseline to 24 weeks. Secondary end points included comparisons of change for the Rhinosinusitis Disability Index (RSDI) and the Sino-Nasal Outcome Test (SNOT-20). Results A total of 198 patients were enrolled (146 surgery and 52 MM). Of the patients who chose BSD, 72% (105/146) had their procedures completed in an office setting. Overall, BSD instruments were successful in dilating 97.6% of targeted sinuses (561/575). Patients who chose BSD showed a significantly greater improvement in the Chronic Sinusitis Survey score versus MM (42.0 versus 27.0, p < 0.001). Results from the RSDI and SNOT-20 surveys showed similar improvements for surgery versus MM (RSDI, 36.0 versus 18.1, p < 0.001; SNOT-20, 1.7 versus 1.0, p < 0.002). Conclusion Patients who selected sinus surgery in which BSD instruments were used on the peripheral sinuses demonstrated significantly greater improvements in quality of life compared with those who elected ongoing MM. These results were achieved through office-based procedures with the patient under local anesthesia in the majority of patients.

This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology-Head and Neck Surgery featuring the updated "Clinical Practice Guideline: Otitis Media with Effusion." To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 18 recommendations developed emphasize diagnostic accuracy, identification of children who are most susceptible to developmental sequelae from otitis media with effusion, and education of clinicians and patients regarding the favorable natural history of most otitis media with effusion and the lack of efficacy for medical therapy (eg, steroids, antihistamines, decongestants). An updated guideline is needed due to new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

SUMMARY Human rhinoviruses cause the common cold and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross-protect across multiple rhinovirus strains. To analyze rhinovirus-specific B cell responses in humans, we developed techniques using intact RV-A16 and RV-A39 for high-throughput high-dimensional single-cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T-bet+ B cells binding both viruses that account for ~5% of CXCR5− memory B cells. These B cells infiltrate nasal tissue and expand in the blood after infection. Their rapid secretion of heterotypic immunoglobulin G (IgG) in vitro, but not IgA, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA, mirroring the systemic response. Temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re-infection., In Brief Eccles et al. demonstrate a key role for T-bet+ B cells in rapid local cross-reactive immunoglobulin G (IgG) responses to rhinovirus, whereas strain-specific B cells that are phenotypically distinct match systemic antibodies found later. This might explain efficient clearance of virus in the acute phase but narrow protection and continued susceptibility after the infection clears., Graphical Abstract

Nasopharyngeal angiofibroma (NA) is a benign, highly vascularised tumour of the nasopharynx, which typically occurs in young males aged 14-25 years. We report an interesting case of an NA arising de novo in a 32-year-old male. He was referred to our facility for severe nasal haemorrhage after biopsy of a left nasopharyngeal mass. In the operating room, extensive bleeding was noted, and an endoscopic medial maxillectomy was performed, and the left internal maxillary artery was ligated allowing for near total resection of the lesion. The pathological specimen confirmed the diagnosis of NA. To our knowledge, this is one of the oldest patients presenting with a de novo NA, in his fourth decade of life, confirming that this diagnosis must be considered in all those with large nasopharyngeal masses.

Objective To develop a clinical consensus statement on the use of sinus ostial dilation (SOD) of the paranasal sinuses. Methods An expert panel of otolaryngologists was assembled to represent general otolaryngology and relevant subspecialty societies. The target population is adults 18 years or older with chronic or recurrent rhinosinusitis (with or without nasal polyps, with or without prior sinus surgery) for whom SOD is being recommended, defined as endoscopic use of a balloon device to enlarge or open the outflow tracts of the maxillary, frontal, or sphenoid sinuses, as a standalone procedure or with endoscopic surgery. A modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus. Results After 3 iterative Delphi method surveys, 13 statements met the standardized definition of consensus while 45 statements did not. The clinical statements were grouped into 3 categories for presentation and discussion: (1) patient criteria, (2) perioperative considerations, and (3) outcomes. Strong consensus was obtained for not performing SOD in patients without sinonasal symptoms or positive findings on computed tomography (CT) in patients with symptoms only of headache or sleep apnea without criteria for sinusitis. In addition, strong consensus was met that CT scan of the sinuses was necessary before performing SOD and that surgeons need to understand and abide by regulations set forth by the US Food and Drug Administration if they choose to reuse/reprocess devices. Conclusion Expert panel consensus may provide helpful information for the otolaryngologist considering the use of SOD for the management of patients with a diagnosis of rhinosinusitis. This panel reached consensus on a number of statements that defined the use of SOD as inappropriate in the management of a variety of symptoms or diseases in the absence of underlying sinusitis. When patients meet the definition of chronic sinusitis as confirmed by CT scan, SOD of the sinuses can be indicated and/or effective in certain scenarios. Additional consensus statements regarding proper setting and safeguards for performing the procedure are described.

OBJECTIVERathke cleft cysts (RCCs) are sellar lesions that are commonly encountered in adults but infrequently diagnosed in the pediatric population. As a result, the optimal management of pediatric RCCs remains a subject of controversy. Only 2 prior surgical series have been published on pediatric RCCs and no study has compared the presentation and outcomes of surgically versus conservatively managed cases. The authors therefore performed a comparative analysis of pediatric cases of RCC in which patients were treated with surgery or managed in a conservative manner.METHODSAll cases involving pediatric patients diagnosed with an RCC at the University of Virginia between 2000 and 2016 were included in this study. Patient medical records, operative notes, and neuroimaging findings were reviewed. Patients who developed visual field deficits, radiographic evidence of chiasmal compression, or medically refractory headaches were considered candidates for surgical intervention. All patients who were selected for surgery underwent an endoscopic endonasal approach with cyst fenestration.RESULTSA total of 24 pediatric patients were diagnosed with an RCC over a 16-year period. Seven patients ultimately underwent transsphenoidal cyst fenestration, and 17 were managed conservatively. The patients’ age at diagnosis, cyst size, and pituitary function at the time of RCC diagnosis were similar in the conservatively and surgically managed cohorts. At diagnosis, 19 of 24 patients endorsed headaches that led to neuroimaging. All patients in the surgical cohort endorsed severe headaches at diagnosis compared with 71% in the conservative group. For the 7 patients treated with surgery, complete cyst evacuation was achieved in 86% of cases. Transient postoperative endocrinopathy occurred in 4 (57%) of 7 surgically treated individuals and resolved in all cases. In the conservative cohort, 1 patient developed a delayed pituitary-related endocrinopathy. Headache resolution occurred in 5 (71%) of the 7 patients who underwent surgery and 7 (58%) of the 12 who were treated without surgery. Cyst recurrence was documented in 1 individual in the surgical cohort who underwent a subtotal cyst fenestration that ultimately required re-intervention. In the conservative cohort, spontaneous cyst shrinkage occurred in 35% of patients with a median time to regression of 23.5 months.CONCLUSIONSPediatric RCCs are benign sellar lesions that often present with headaches. While cyst fenestration mitigates headaches in most patients, the majority of conservatively managed pediatric patients with RCCs will have spontaneous headache resolution. Furthermore, spontaneous RCC regression occurs in a substantial number of individuals. Thus, in the absence of optic compression, visual field deficit, or diagnostic uncertainty, many pediatric cases of RCC can be managed conservatively.

Objectives/Hypothesis The frontal sinus is one of the most anatomically complex and inaccessible of the paranasal sinuses. As a result, surgeons have continually tried to improve surgical management of the frontal sinus. The senior author (c.w.g.) shares 50 years of experience managing the frontal sinus. Data Sources PubMed literature search. Review Methods Review of the literature regarding landmark innovations in frontal sinus surgery. Results Open approaches established that the frontal sinus is accessible, and in certain circumstances, such as with large osteoma or papilloma, are still required. The endoscope changed the surgical landscape and allowed for greater finesse and decreased morbidity. Sinus balloon dilation is the newest change in frontal sinus management and shows promise in properly selected cases. Conclusion Surgery of the frontal sinus continues to evolve and improve. Although there are new techniques, the older techniques are still pertinent. Laryngoscope, 126:802–807, 2016

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE ( 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE ( 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgELLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.

Studies demonstrate the existence of novel receptors for cysteinyl leukotrienes (CysLTs) that are responsive to leukotriene (LT) E4 and might be pathogenic in aspirin-exacerbated respiratory disease (AERD) asthma. Given the eosinophilic infiltration in this disorder, we investigated eosinophil expression of P2Y12 and gpr99 and their capacity to respond to LTE4. Receptor transcript expression was investigated via quantitative PCR and surface protein expression via flow cytometry. We investigated LTE4 influences on eosinophils including Ca+2 flux, cAMP induction, modulation of adhesion molecule expression, apoptosis and degranulation. Eosinophils displayed both transcript and surface protein expression of P2Y12 and gpr99. We could not find evidence of LTE4 activation of eosinophils, however, LTE4 induced cAMP expression, and preincubation of eosinophils with LTE4 inhibited degranulation. Even though eosinophils are an important source of CysLTs in AERD, eosinophils are not themselves the pro-inflammatory biological target and, in contrast, LTE4 via cAMP primarily elicits anti-inflammatory responses.

Object The object of this study was to compare surgical outcomes and complications in a contemporaneous series of patients undergoing either microscopic or endoscopic transsphenoidal surgery for nonfunctioning pituitary macroadenomas without imaging evidence of cavernous sinus invasion. Methods This is a retrospective analysis of a prospectively collected database from a single institution. Data were collected from patients whose surgery had occurred in the period from June 2010 to January 2013. Patients who underwent microscopic or endoscopic surgery for Knosp Grade 0, 1, or 2 nonfunctioning pituitary macroadenomas were included in the study. Patients who had clinically secreting or Knosp Grade 3 or 4 tumors and patients who were undergoing revision surgery were excluded from analysis. Eligible patient records were analyzed for outcomes and complications. Statistical analyses were performed on tumor volume, intraoperative factors, postoperative complications, and degree of resection on 1-year postoperative MRI. The results were used to compare the outcomes after microscopic and endoscopic approaches. Results Forty-three patients underwent microscopic transsphenoidal surgery, and 56 underwent endoscopic transsphenoidal surgery. There were no statistical differences in the intraoperative extent of resection or endocrinological complications. There were significantly more intraoperative CSF leaks in the endoscopic group (58% vs 16%); however, there was no difference in the incidence of postoperative CSF rhinorrhea (12% microscopic vs 7% endoscopic). Length of hospitalization was significantly shorter in patients undergoing an endoscopic approach (3.0 days vs 2.4 days). Two-month follow-up imaging was available in 95% of patients, and 75% of patients had 1-year follow-up imaging. At 2 months postprocedure, there was no evidence of residual tumor in 79% (31 of 39) and 85% (47 of 55) of patients in the microscopic and endoscopic groups, respectively. At 1 year postprocedure, 83% (25 of 30) of patients in the microscopic group had no evidence of residual tumor and 82% (36 of 44) of those in the endoscopic group had no evidence of residual tumor. Conclusions The microscopic and endoscopic techniques provide similar outcomes in the surgical treatment of Knosp Grades 0–2 nonfunctioning pituitary macroadenomas.

A retrospective study was conducted to determine if physicians in otolaryngology practice adhered to the clinical practice guideline for adult sinusitis that had been issued by the American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) 3 years earlier. We analyzed data obtained from the charts of 90 adults who had presented to an otolaryngology outpatient department with a diagnosis of chronic rhinosinusitis (CRS), acute bacterial rhinosinusitis (ABRS), or acute viral rhinosinusitis (AVRS); there were 76 cases of CRS, 11 cases of ABRS, and 3 cases of AVRS. Our goal was to ascertain how closely the treating physician had adhered to the AAO-HNS recommendations with respect to diagnosis, treatment, and prevention of these diseases. The study group was made up of 10 otolaryngologists. We evaluated 7 clinical practice metrics for CRS, 7 metrics for ABRS, and 3 for AVRS. We found that individual physician adherence rates for cases of CRS ranged from 0 to 100%; average scores for the 7 metrics ranged from 4 to 88%. For cases of ABRS, adherence scores ranged from 0 to 100%; average scores for the 7 metrics ranged from 0 to 41 %. For AVRS, the rate of adherence for all 3 metrics was 0%. This study revealed wide variations in adherence to the AAO-HNS guideline, but overall adherence was generally poor. Adherence appeared to be worse for the acute types of rhinosinusitis than for chronic rhinosinusitis. In view of these findings, a worksheet was developed that clinicians could use to improve compliance with the guidelines.

Reactions to aspirin and nonsteroidal anti-inflammatory drugs in patients with aspirin-exacerbated respiratory disease (AERD) are triggered when constraints upon activated eosinophils, normally supplied by PGE2, are removed secondary to cyclooxygenase-1 inhibition. However, the mechanism driving the concomitant cellular activation is unknown. We investigated the capacity of aspirin itself to provide this activation signal. Eosinophils were enriched from peripheral blood samples and activated with lysine ASA (LysASA). Parallel samples were stimulated with related nonsteroidal anti-inflammatory drugs. Activation was evaluated as Ca2+ flux, secretion of cysteinyl leukotrienes (CysLT), and eosinophil-derived neurotoxin (EDN) release. CD34+ progenitor-derived mast cells were also used to test the influence of aspirin on human mast cells with measurements of Ca2+ flux and PGD2 release. LysASA induced Ca2+ fluxes and EDN release, but not CysLT secretion from circulating eosinophils. There was no difference in the sensitivity or extent of activation between AERD and control subjects, and sodium salicylate was without effect. Like eosinophils, aspirin was able to activate human mast cells directly through Ca2+ flux and PGD2 release. AERD is associated with eosinophils maturing locally in a high IFN-γ milieu. As such, in additional studies, eosinophil progenitors were differentiated in the presence of IFN-γ prior to activation with aspirin. Eosinophils matured in the presence of IFN-γ displayed robust secretion of both EDN and CysLTs. These studies identify aspirin as the trigger of eosinophil and mast cell activation in AERD, acting in synergy with its ability to release cells from the anti-inflammatory constraints of PGE2.

Background The purpose of the study was to determine the age at which initiation of specific subcutaneous immunotherapy (SCIT) becomes more cost-effective than continued lifetime intranasal steroid (NS) therapy in the treatment of allergic rhinitis, with the use of a decision analysis model. Methods A Markov decision analysis model was created for this study. Economic analyses were performed to identify “break-even” points in the treatment of allergic rhinitis with the use of SCIT and NS. Efficacy rates for therapy and cost data were collected from the published literature. Models in which there was only incomplete improvement while receiving SCIT were also evaluated for economic break-even points. The primary perspective of the study was societal. Results Multiple break-even point curves were obtained corresponding to various clinical scenarios. For patients with seasonal allergic rhinitis requiring NS (i.e., fluticasone) 6 months per year, the age at which initiation of SCIT provides long-term direct cost advantage is less than 41 years. For patients with perennial rhinitis symptoms requiring year-round NS, the cut-off age for SCIT cost-effectiveness increases to 60 years. Hypothetical subjects who require continued NS treatment (50% reduction of previous dosage) while receiving SCIT also display break-even points, whereby it is economically advantageous to consider allergy referral and SCIT, dependent on the cost of the NS prescribed. Conclusion The age at which SCIT provides economic advantages over NS in the treatment of allergic rhinitis depends on multiple clinical factors. Decision analysis models can assist the physician in accounting for these factors and customize patient counseling with regard to treatment options.

It is unclear whether endoscopic transsphenoidal surgery (ETSS) or microsurgical transsphenoidal surgery (MTS) is a superior surgical approach for pituitary adenomas.The objective of the study was to compare the outcome of surgery with ETSS and MTS by experienced pituitary surgeons using criteria of remission using current consensus criteria for acromegaly.This was a retrospective review of prospectively recorded outcomes. The study was conducted at a tertiary referral center. Patients, Interventions, and Outcome Measures: Remission was defined as a normal IGF-I level and either suppressed GH less than 0.4 ng/mL during an oral glucose tolerance test or random GH less than 1.0 ng/mL. The Youden indices were calculated to determine the optimal cutoffs for using immediate postoperative GH levels to predict the results of later testing for remission.Preoperative demographics and tumor characteristics were not significantly different between patients undergoing ETSS (72 patients) or MTS (41 patients). Overall, postoperative remission was achieved in 20 of 23 microadenomas (87%) and 59 of 90 macroadenomas (66%). Remission rates and perioperative complications were not significantly different between ETSS and MTS groups, except for self-reported sinusitis and alterations in taste or smell, which were significantly higher in patients treated with ETSS. Preoperative variables predicting remission in multivariate analysis included GH less than 45 ng/mL [odds ratio (OR) 6.4, P = .010)] and Knosp score of 0-2 (OR 6.8, P.001). Postoperative in-hospital GH less than 1.15 ng/mL provided the best predictor of remission (OR 7.7, P.001; sensitivity of 73%, specificity of 85%) defined by follow-up testing.Outcomes of transsphenoidal surgery for acromegaly by experienced pituitary surgeons do not differ between endoscopic and microscopic techniques. Regardless of the mode of resection, patients with high preoperative GH levels and Knosp scores are less likely to achieve remission. An immediate postoperative GH level of less than 1.15 ng/mL provides the best immediate predictor of remission, but long-term outcomes are indicated.

OBJECTIVE The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods. METHODS The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS). RESULTS The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test). CONCLUSIONS Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.