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Flavones are a class of natural plant secondary metabolites that have anti-inflammatory and anti-bacterial effects. Some flavones also activate the T2R14 bitter taste receptor, which is expressed in motile cilia of the sinonasal epithelium and activates innate immune nitric oxide (NO) production. Flavones may thus be potential therapeutics for respiratory infections. Our objective was to examine the anti-microbial effects of flavones on the common sinonasal pathogens Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa, evaluating both planktonic and biofilm growth. Flavones had only very low-level antibacterial activity alone. They did not reduce biofilm formation, but did reduce production of the important P. aeruginosa inflammatory mediator and ciliotoxin pyocyanin. However, flavones exhibited synergy against P. aeruginosa in the presence of antibiotics or recombinant human lysozyme. They also enhanced the efficacy of antimicrobials secreted by cultured and primary human airway cells grown at air-liquid interface. This suggests that flavones may have anti-gram-negative potential as topical therapeutics when combined with antibiotics or in the context of innate antimicrobials secreted by the respiratory or other epithelia. This may have an additive effect when combined with T2R14-activated NO production. Additional studies are necessary to understand which flavone compounds or mixtures are the most efficacious. [ABSTRACT FROM AUTHOR]

Background Nitric oxide (NO) is released in the airway as a critical component of innate immune defense against invading pathogenic organisms. It is well documented that bacteriostatic and bactericidal effects of NO are concentration-dependent. However, few data exist comparing relative susceptibility of common pathogens to NO at physiologic concentrations. In this study we evaluated the effects of NO on 4 common airway bacteria and 1 fungus, and examined the potential implications of discrepancies in sensitivity. Methods Staphylococcus epidermis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans cultures were adjusted to a uniform optical density (OD) and grown in log phase at 37°C with varying concentrations of NO formed by DETA NONOate. Both OD readings and colony forming units (CFUs) were measured at varying time-points to evaluate for inhibitory effects of NO. Results P aeruginosa and C albicans were significantly more sensitive to NO at physiologic concentrations typical of the human airway. S aureus was attenuated by NO to a lesser degree, and K pneumoniae and S epidermis were more resistant to NO at all concentrations tested. Air surface liquid from cultured human sinonasal epithelial cells had an additive effect in bacterial killing of P aeruginosa, but not in S aureus. Conclusion Common airway pathogens have varying levels of susceptibility to NO at physiologic concentrations of innate immune defense. Relative sensitivity of P aeruginosa and relative resistance of S epidermis may help explain the composition of the healthy microbiome, as well as opportunistic infection in the absence of induced NO release. [ABSTRACT FROM AUTHOR]

Background Off-label use of topical ophthalmologic formulations for treatment of rhinologic disease is cited in recent literature and is anecdotally prevalent among practicing otolaryngologists. Steroids, antibiotics, and other drugs designed for ocular use have subjective clinical efficacy in the nose and sinuses, but their specific effects on the ciliated epithelium are less well defined. This study examines 9 commercially available ophthalmologic drug formulations for effects on ciliary motility in sinonasal cultures, in an effort to characterize their utility as topical therapies for sinonasal diseases. Methods Ophthalmologic solutions were tested on human sinonasal cultures grown at an air-liquid interface. Baseline ciliary beat frequency (CBF) was recorded and compared with CBF changes in the 20 minutes after drug addition. Substances were categorized by degree of ciliostimulation or cilioinhibition. Results All ophthalmologic solutions tested had only moderate effects on CBF during the 20-minute experimental period, with no solutions causing overt ciliostasis. Azithromycin, neomycin, and olopatadine were slightly ciliostimulatory, whereas levofloxacin, tobramycin, dexamethasone, azelastine, and prednisolone acetate were cilioinhibitory. Ciprofloxacin elicited moderate cilioinhibition that progressed to ciliostimulation. Conclusion All solutions tested appear to have moderate effects on ciliated cell surfaces for a period of time typical of mucociliary clearance (10 to 20 minutes). Both active drugs and excipients can play a role in ciliary modulation, and specific formulations can show unique or unexpected properties. Any other individual ophthalmologic solutions to be used in a nasal drug delivery system should be tested in this manner to evaluate potential ciliary effects before clinical use. [ABSTRACT FROM AUTHOR]

Background Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes. Methods Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations. Results There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) ( p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores ( p = 0.012). Conclusion Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ~20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potentially important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and inducible NOS up-regulation as well as cytokine release in primary and cultured airway cells in response to several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (<7 nm) with the T2R38 isoform. Heterologously expressed T2R14 responds to multiple flavones. These flavones also activate T2R14-driven calcium signals in primary cells that activate nitric oxide production to increase ciliary beating and mucociliary clearance. TAS2R38 polymorphisms encode functional (PAV: proline, alanine, and valine at positions 49, 262, and 296, respectively) or nonfunctional (AVI: alanine, valine, isoleucine at positions 49, 262, and 296, respectively) T2R38. Our data demonstrate that T2R14 in sinonasal cilia is a potential therapeutic target for upper respiratory infections and that flavones may have clinical potential as topical therapeutics, particularly in T2R38 AVI/AVI individuals. [ABSTRACT FROM AUTHOR]

Background Squamous cell carcinoma (SCC) of the sinonasal cavity is a rare entity that arises as either de-novo tumors or from inverted papillomas (IPs). In this study we evaluate and compare oncologic outcomes of sinonasal SCCs based on their etiology and treatment strategy. Methods This investigation was a single-center, retrospective review comparing de-novo SCCs (n = 28) and those associated with IPs (n = 38) resected during the period from 2000 to 2015. Demographic and tumor data, surgical approach, recurrence, and clinical outcomes were analyzed. Results There was no statistical difference when comparing age, smoking history, tumor origin, or tumor stage of our patients with de-novo sinonasal SCC (DN-SCC) vs IP-transformed SCC (IP-SCC). IP-SCC tumors demonstrated better overall survival ( p = 0.065) and disease-specific survival ( p = 0.041) compared with DN-SCC. Early T-stage IP-SCC tumors had better disease-free survival compared with early T-stage DN-SCC tumors ( p = 0.002). Distant metastasis was an independent prognostic factor of worse disease-specific survival ( p = 0.002). SCC disease-specific survival was not affected by surgical resection technique. Conclusion SCC tumors arising from IPs appear to have improved disease-specific survival compared with de-novo sinonasal SCC tumors. The oncologic differences between the 2 groups are found primarily among the early-stage tumors. [ABSTRACT FROM AUTHOR]

Background An ectopic pituitary adenoma presenting as a clival or sphenoidmass is a rare clinical occurrence that may mislead the clinician and result in unnecessary interventions or potential medicolegal consequences. Here, we present one of the largest multi-institutional case series and review the literature with an emphasis on radiological findings and critical preoperative workup. Methods Retrospective chart review. Results Nine patients were identified with ectopic pituitary adenomas of the sphenoid or clivus. There were four females and five males. Median age was 60 years old (range, 36-73 years). The most common presenting symptom was headache (56%). Five (56%) patients presented with a mass arising fromthe clivus while four (44%) presented with a mass in the sphenoid. Six (67%) patients demonstrated biochemical evidence of hypersecretion on full endocrinology panel. All masses showed evidence of enhancement with gadolinium with a propensity for adjacent bone involvement. Lesions also had a predilection for growth toward the cavernous sinus, carotid artery, or sellar floor. Surgical intervention was performed in eight patients (89%). In eight patients (89%), tumors demonstrated immunoreactivity to prolactin. Conclusions Pituitary adenomas can rarely present as an isolated sphenoid or clival mass. Lesions displayed similar magnetic resonance imaging findings with an erosive growth pattern toward the sellar floor, cavernous sinus, or adjacent carotid artery. Patients with clival or parasellar lesions with comparable features should have a preoperative workup which includes prolactin level and alert the physician to consider an ectopic pituitary adenoma in the differential to prevent unnecessary surgery and potential complications. [ABSTRACT FROM AUTHOR]

Background Antimicrobial peptides (AMPs) produced by the epithelium are important for innate immune defense. In 2001, a novel AMP dermcidin (DCD) was described with no homology to other AMPs and an expression pattern restricted to eccrine sweat glands. In contrast to other AMPs, DCD expression has not been shown to be induced under inflammatory conditions in the skin. After identifying DCD by mass spectrometry in a protein sample isolated from human nasal secretions, we sought to determine the role of DCD in innate defense of the sinonasal airway. Methods After institutional review board approval, sinonasal mucosal tissue specimens were acquired from residual clinical material obtained during sinonasal surgery and used to grow cultures in an air-liquid interface environment. After stimulation of the cultures with various bitter compounds and phosphate-buffered saline, airway surface liquid was collected, and a DCD-specific enzyme-linked immunoassay was used to quantify DCD in each sample. To localize DCD expression, ALI cultures were fixed and immunofluorescence performed against DCD, β-tubulin IV, and Muc-5A. Results Enzyme-linked immunoassay showed DCD in air-surface liquid and in clinical nasal secretion samples at concentrations comparable to eccrine sweat. There was no evidence of inducible expression with any of the tested stimulants. Confocal microscopy revealed DCD expression in sinonasal mucosal goblet cells. Conclusion This is the first report of the presence of DCD in nasal mucosa and demonstration of DCD in clinical samples of human nasal secretions at clinically relevant concentrations, which may represent a novel arm of sinonasal airway innate defense. [ABSTRACT FROM AUTHOR]

Background Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18F-fluorodeoxyglucose (18FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population. Methods A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18FDG PET/CT standardized uptake value data were collected and compared between various time-points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test. Results A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months ( p = 0.048) as well as 2 to 4 and 5 to 24 months ( p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months ( p = 0.083). Conclusion Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies. [ABSTRACT FROM AUTHOR]

Background Nitric oxide (NO) is produced by sinonasal epithelial cells as part of the innate immune response against bacteria. We previously described bitter-taste-receptor-dependent and -independent NO responses to product(s) secreted by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized that sinonasal epithelium would be able to detect the gram-positive, coagulase-negative bacteria Staphylococcus epidermidis and mount a similar NO response. Methods Sinonasal air-liquid interface cultures were treated with conditioned medium (CM) from lab strains and clinical isolates of coagulase-negative staphylococci and S aureus. NO production was quantified by fluorescence imaging. Bitter taste receptor signaling inhibitors were utilized to characterize the pathway responsible for NO production in response to S epidermidis CM. Results S epidermidis CM contains a low-molecular-weight, heat, and protease-stabile product that induces an NO synthase (NOS)-mediated NO production that is less robust than the response triggered by S aureus CM. The S epidermidis CM-stimulated NO response is not inhibited by antagonists of phospholipase C isoform β-2 nor the transient receptor potential melastatin isoform 5 ion channel, both critical to bitter taste signaling. Conclusion This study identifies an NO-mediated innate defense response in sinonasal epithelium elicited by S epidermidis product(s). The active bacterial product is likely a small, nonpeptide molecule that stimulates a pathway independent of bitter taste receptors. Although the NO response to S epidermidis is less vigorous compared with S aureus, the product(s) share similar characteristics. Together, the responses to staphylococci species may help explain the pathophysiology of upper respiratory infections. [ABSTRACT FROM AUTHOR]

Background The gold standard of treatment for esthesioneuroblastoma consists of en bloc craniofacial resection with postoperative therapy dictated by histology and tumor extent. Numerous studies have shown fully endoscopic approaches to provide comparable survival and recurrence rates with decreased patient morbidity. Here we report the first multi-institutional series assessing smell outcomes of patients who underwent unilateral endoscopic resection of esthesioneuroblastoma with preservation of the contralateral olfactory bulb. Methods A multi-institutional retrospective review was performed identifying patients who underwent endoscopic unilateral resection of esthesioneuroblastoma with preservation of 1 olfactory bulb between 2003 and 2015. After completion of postoperative radiation, patients were administered the University of Pennsylvania Smell Identification Test (UPSIT) to assess olfactory function. Results Fourteen patients (7 males, 7 females) were identified and tested for posttreatment olfactory function. All 14 patients received postoperative radiotherapy and 4 patients received additional chemotherapy. Mean follow-up time was 51.7 months. There was no disease recurrence. Six patients (43%) were found to have residual smell function with 2 patients (14%) having normal or mildly reduced smell function. Conclusion Here we report the first multi-institutional series demonstrating smell preservation after unilateral endoscopic resection of esthesioneuroblastoma. In carefully selected patients, this approach can yield comparable survival with decreased patient morbidity. [ABSTRACT FROM AUTHOR]

Background:Risk of nodal involvement in patients with squamous cell carcinomas (SCC) of the nasal cavity and maxillary sinus has not been well defined, especially by risk factors beyond local T-stage. Additional criteria defining patients at highest risk, as well as specific nodal levels at highest risk, has been limited in small retrospective series. We describe a population-based assessment of specific nodal involvement in this group. Material and methods:The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2010 identified 1283 eligible patients with SCC of the nasal cavity or maxillary sinus. Neck involvement and individual nodal level involvement at presentation were assessed, and comparison made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. Results:Among 1283 patients, 182 (14.2%) had nodal involvement at presentation (4–27% by site and local extension). T-stage alone was associated with higher rates of nodal involvement in maxillary sinus SCC, while higher T-stage and size >2 cm were associated with higher rates of nodal involvement in nasal cavity SCC on multivariable analysis. Facial nodes and cervical nodes at levels 1 and 2 have the highest rates of involvement in T4a nasal cavity SCC, whereas nodal levels 1, 2, and/or 3 have the highest rates of involvement in T2 or higher maxillary sinus SCC when compared with a clinical reference standard. Conclusion:In this population-based study, there are high rates of initial nodal involvement when stratified by local extent determined by T-stage in nasal cavity SCC and maxillary sinus SCC, and independently by size in nasal cavity SCC. Involvement of the facial and nodal levels 1–3 varies depending on site and local extent of tumor involvement. These observations may help guide treatment decision making in the inclusion of and extent of elective nodal treatment fields. [ABSTRACT FROM AUTHOR]

Background Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed. Methods Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients. Results Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings ( p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients ( p = 0.0026). Conclusion In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients. [ABSTRACT FROM AUTHOR]

An abstract of a study which examined patients undergoing extended endoscopic approach (EEA) for skull base tumors is presented.

Middle meatal spacers are used by many sinus surgeons to aid postoperative care. Aspiration of a spacer is a concern. We demonstrate a novel method of securing spacers with a transseptal suture to prevent aspiration. We fashion each spacer from a powder-free, nonlatex glove finger that is packed with a Merocel sponge. The open end of the finger is closed with 2-0 Prolene sutures. For a bilateral procedure, the needle is left attached to one of the spacers. A spacer is placed in each ethmoid cavity, the attached needle is passed through the anterior cartilaginous septum, and the suture is tied to the suture on the opposite spacer. For unilateral procedures, the suture on the single spacer is passed to the contralateral side and tied on itself One week later, the transseptal suture is cut and the spacers are removed. We performed this procedure on 78 patients who had undergone total ethmoidectomy. None of the spacers migrated during the I week they were in place. One patient complained of pain during removal of a spacer. During follow-up of 2 to 10 months, we found no evidence of injury to the septum at the site of the transseptal suture. We conclude that the transseptal suture is a safe and cosmetically superior method of securing middle meatal spacers. [ABSTRACT FROM AUTHOR]

Background Investigations into the distribution of sinus irrigations have been limited by labor-intensive methodologies that do not capture the full dynamics of irrigation flow. The purpose of this study was to validate the accuracy of a computational fluid dynamics (CFD) model for sinonasal irrigations through a cadaveric experiment. Methods Endoscopic sinus surgery was performed on 2 fresh cadavers to open all 8 sinuses, including a Draf III procedure for cadaver 1, and Draf IIb frontal sinusotomies for cadaver 2. Computed tomography maxillofacial scans were obtained preoperatively and postoperatively, from which CFD models were created. Blue-dyed saline in a 240-mL squeeze bottle was used to irrigate cadaver sinuses at 60 mL/second (120 mL per side, over 2 seconds). These parameters were replicated in CFD simulations. Endoscopes were placed through trephinations drilled through the anterior walls of the maxillary and frontal sinuses, and sphenoid roofs. Irrigation flow into the maxillary, frontal, and sphenoid sinuses was graded both ipsilateral and contralateral to the side of nasal irrigation, and then compared with the CFD simulations. Results In both cadavers, preoperative and postoperative irrigation flow into maxillary, frontal, and sphenoid sinuses matched extremely well when comparing the CFD models and cadaver endoscopic videos. For cadaver 1, there was 100% concordance between the CFD model and cadaver videos, and 83% concordance for cadaver 2. Conclusion This cadaveric experiment provided potential validation of the CFD model for simulating saline irrigation flow into the maxillary, frontal, and sphenoid sinuses before and after sinus surgery. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients. Methods ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment. Results A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05). Conclusion Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients. [ABSTRACT FROM AUTHOR]

Objective: Risk of nodal involvement in patients with sinonasal small-cell carcinoma and sinonasal undifferentiated carcinoma (SNUC) has not been well defined because of their rarity. We describe a population-based assessment of specific nodal level involvement in this group of rare neuroectodermal tumours. Methods: The Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2011 identified patients with SNUC and sinonasal small-cell carcinoma. Overall neck involvement and individual nodal level involvement at presentation were assessed, and comparison was made with a contemporaneous cohort of patients with a borderline clinically significant risk of nodal involvement and recurrence. Results: Of 141 patients, 31 (22%) had gross nodal involvement at presentation (range 14-33% by site and histology). Non-nasal, non-ethmoid site with SNUC histology has the highest rates of initial nodal involvement, whereas higher stage and size do not predict for higher nodal involvement rates. Bilateral Levels 2-3 for all sinonasal small cell; Levels 2-3 for nasal or ethmoid SNUC; and bilateral Levels 1-3 in non-nasal/non-ethmoid SNUC have the highest rates of involvement compared with a clinical reference standard. Conclusion: We found high rates of initial nodal involvement in all SNUC and sinonasal small-cell carcinoma. We found higher initial involvement of Levels 2 and 3 and in certain cases to the Level 1 nodal levels, hypothesizing benefit for elective treatment to those levels. Advances in knowledge: With small single-institution series reporting conflicting nodal involvement rates, our data support high rates of nodal presentation at diagnosis, hypothesizing benefit for elective nodal treatment in this cohort. [ABSTRACT FROM AUTHOR]

Background Nitric oxide (NO) is an important antibacterial defense molecule produced by upper airway (sinonasal) epithelial cells. We previously showed that a bitter taste receptor expressed in airway epithelium detects quorum-sensing molecules secreted by Gram-negative bacteria and subsequently triggers bactericidal NO production. We hypothesized that the upper airway epithelium may also be able to detect the Gram-positive aerobe Staphylococcus aureus and mount an NO response. Methods Human sinonasal air-liquid interface (ALI) cultures were treated with methicillin-resistant S. aureus (MRSA)-conditioned medium (CM), and NO production was measured using fluorescence imaging. Inhibitors of bitter taste receptor signaling were used to pharmacologically determine if this pathway was involved in the production of NO. Results A low-molecular-weight, heat, and protease-stabile product found in MRSA CM induced differential, NO synthase (NOS)-mediated NO production. This response varied markedly between individual patients. The MRSA-stimulated NO production was not dependent on 2 important components of bitter taste signaling: phospholipase C isoform β-2 or the transient receptor potential melastatin isoform 5 (TRPM5) ion channel. Conclusion This study shows that a S. aureus product elicits an NO-mediated innate defense response in human upper airway epithelium. The active bacterial product is likely a small, nonpeptide molecule that triggers a pathway independent of bitter taste receptors. Patient variation in the NO response to MRSA product(s), potentially due to genetic differences, might play a role in pathophysiology of Gram-positive upper respiratory infections and/or pathogenesis of chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS. Methods Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed. Results A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions. Conclusion S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes. [ABSTRACT FROM AUTHOR]

Background It remains unclear how much chronic rhinosinusitis (CRS) patients with bacterial biofilms can benefit from functional endoscopic sinus surgery (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with quality of life (QOL) improvement after FESS. Methods This retrospective cohort study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus samples were taken to evaluate for biofilm-formation in vitro using a modified Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3-month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Patients' characteristics and medications were collected. Clinical significant QOL change was defined as a difference of at least 0.5 standard deviation (SD) of baseline SNOT-22 score in the reference group. Results A total of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24). Patients with biofilm-forming bacteria had significantly worse preoperative SNOT-22 scores compared to patients without biofilm-forming bacteria (48 ± 20 vs 38 ± 23, p = 0.048). Both groups had clinically significant QOL improvement after FESS, and the differences in their 1-month (23 ± 19 vs 17 ± 20) and 3-month (27 ± 18 vs 18 ± 19) post-FESS SNOT-22 scores were not significant. However, patients with biofilm-forming bacteria demonstrated significantly less QOL improvement than patients without biofilm-forming bacteria from pre-FESS to 6-month post-FESS visits after adjusting for clinical factors (35 ± 25 vs 14 ± 15; β-coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p = 0.016). Conclusion CRS patients with biofilm-forming bacteria demonstrated clinically significant QOL improvement following FESS, but the degree of improvement was decreased overtime and became significantly worse than patients without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was independent of other risk factors for CRS. [ABSTRACT FROM AUTHOR]

Background Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity. Methods Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture. Results A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034). Conclusion Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates. [ABSTRACT FROM AUTHOR]

Background It is unclear whether chronic rhinosinusitis (CRS) patients with both nasal polyps and asthma have different quality of life (QOL) improvement after functional endoscopic sinus surgery (FESS). We aimed to determine whether CRS patients with asthma and nasal polyps had a greater QOL improvement after FESS compared to patients without asthma or polyps. Methods This retrospective analysis included adult CRS patients who underwent FESS between 2007 and 2011. QOL was measured using the 22-item Sino-Nasal Outcome Test (SNOT-22). Variables collected included baseline demographics, clinical factors, SNOT-22 scores before FESS, and 1 month, 3 months, and 6 months post-FESS. Groups tested were asthma alone, polyps alone, asthma and polyps, and no asthma or polyps. Linear mixed-effects regression model was performed to calculate β-coefficients, which represent the adjusted mean QOL differences. Results Among the 376 patients included, 40.16% had both asthma and polyps (n = 151), 14.36% had asthma alone (n = 54), 19.45% had polyps alone (n = 75), and 25.53% had no asthma or polyps (n = 96). After adjusting for all factors, there were significantly more QOL improvements in patients with both asthma and nasal polyps from baseline to 1-month (β-coefficient = −10.05; 95% CI, −15.86 to −4.23; p = 0.001) and 3-month follow-up (β-coefficient = −8.27; 95% CI, −14.98 to −1.56; p = 0.016), and patients with asthma alone from baseline to 6-month follow-up (β-coefficient = −8.78; 95% CI, −17.45 to −0.11; p = 0.047), when compared to patients without asthma or nasal polyps. Conclusion CRS patients with both asthma and nasal polyps or asthma alone experience a larger QOL benefit from FESS immediately after FESS compared to CRS patients without asthma or polyps. [ABSTRACT FROM AUTHOR]

Background Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS). Methods We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis. Results Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p = 0.004) and Gram-negative rods (26.32% vs 8.96%; p = 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS. Conclusion DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM. [ABSTRACT FROM AUTHOR]

Bitter taste receptors (T2Rs) in the human airway detect harmful compounds, including secreted bacterial products. Here, using human primary sinonasal air-liquid interface cultures and tissue explants, we deter- mined that activation of a subset of airway T2Rs expressed in nasal solitary chemosensory cells activates a calcium wave that propagates through gap junctions to the surrounding respiratory epithelial cells. The T2R-dependent calcium wave stimulated robust secretion of antimicrobial peptides into the mucus that was capable of killing a variety of respiratory pathogens. Furthermore, sweet taste receptor (T1R2/3) activation suppressed T2R-mediated antimicrobial peptide secretion, suggesting that T1R2/3-mediated inhibition of T2Rs prevents full antimicrobial peptide release during times of relative health. In contrast, during acute bacterial infection, T1R2/3 is likely deactivated in response to bacterial consumption of airway surface liquid glucose, alleviating T2R inhibition and resulting in antimicrobial peptide secretion. We found that patients with chronic rhinosinusitis have elevated glucose concentrations in their nasal secretions, and other reports have shown that patients with hyperglycemia likewise have elevated nasal glucose levels. These data suggest that increased glucose in respiratory secretions in pathologic states, such as chronic rhinosinusitis or hyperglycemia, promotes tonic activation of T1R2/3 and suppresses T2R-mediated innate defense. Furthermore, targeting T1R2/3-dependent suppression of T2Rs may have therapeutic potential for upper respiratory tract infections. [ABSTRACT FROM AUTHOR]

Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms. [ABSTRACT FROM AUTHOR]

Mucociliary clearance (MCC) is the primary physical airway defense against inhaled pathogens and particulates. MCC depends on both proper fluid/ mucus homeostasis and epithelial ciliary beating. Vasoactive intestinal peptide (VIP) is a neurotransmitter expressed in the sinonasal epithelium that is up-regulated in allergy. However, the effects of VIP on human sinonasal physiology are unknown, as are VIP's interactions with histamine, a major regulator of allergic disease. We imaged ciliary beat frequency, mucociliary transport, apical Cl- permeability, and airway surface liquid (ASL) height in primary human sinonasal air-liquid-interface cultures to investigate the effects of VIP and histamine. VIP stimulated an increase in ciliary beat frequency (EC50 0.5 µM; maximal increase -40% compared with control) and cystic fibrosis transmem-brane conductance regulator (CFFR)-dependent and Na+K+2Cl- cotransporter-dependent fluid secretion, all requiring cAMP/PKA signaling. Histamine activated Ca2+ signaling that increased ASL height but not ciliary beating. Low concentrations of VIP and histamine had synergistic effects on CFrR-dependent fluid secretion, revealed by increased ASL heights. An up-regulation of VIP in histamine-driven allergic rhinitis would likely enhance mucosal fluid secretion and contribute to allergic rhinorrhea. Conversely, a loss of VIP-activated secretion in patients with CF may impair mucociliary transport, contributing to increased incidences of sino-nasal infections and rhinosinusitis. [ABSTRACT FROM AUTHOR]

The article describes three cases of intravascular papillary endothelial hyperplasia of the skull base and intracranial compartment. The first case involves a 56-year-old woman who presented with chronic, recurrent sinus infections. The second case involves a 39-year-old woman who presented with multiple syncopal episodes and chose surgical removal of the lesion. The third case involves a 73-year-old man who presented with intractable seizures.

Abstract: Introduction: Postoperative CSF leak is the most common complication of endoscopic endonasal approach (EEA) to skull base lesions. Endoscopic multilayer closure of skull base defect using pedicled nasoseptal flaps (NSF) based off the sphenopalatine artery reduces CSF leaks. EEA robustly expands in surgical arena, yet postoperative imaging evaluation remains poorly studied. This work illustrates normal MR imaging appearance of skull base reconstruction utilizing NSFs during immediate postoperative period. Methods: We retrospectively identified patients who had skull base reconstructions utilizing NSFs following EEAs and immediate postoperative-enhanced brain MRI. NSFs and free grafts were evaluated for signal intensity, thickness, configuration, enhancement, vascular pedicle of NSF, relationship in multilayer reconstruction, and defect coverage. Imaging findings were correlated with surgical technique and CSF leaks. Results: Twenty-eight patients had 26 multilayer reconstructions and 34 NSFs. Twenty-nine NSFs showed enhancing C-shaped arc at the skull base. Of those, 26 flaps (90%) were confidently identified by visualization of their vascular pedicles, 3 were not distinguishable from adjacent mucosa and pedicles were not identified. Five NSFs showed no enhancement (1 CSF leak). Twenty-seven enhancing NSFs approximated defects with close abutment to free grafts. One flap was displaced; one incompletely covered the defect (2 CSF leaks). Fisher exact test demonstrated an association between incomplete defect coverage and displacement of NSFs with CSF leak (P =0.05). Conclusion: Endoscopic skull base reconstruction utilizing NSF has characteristic MR imaging appearance. Non-enhancing mucosal gap or displacement of NSF may indicate incomplete defect coverage, identifying patients at risk for CSF leak. [Copyright &y& Elsevier]

Objectives: Malignant tumors of the paranasal sinuses are traditionally approached by a variety of external incisions. Recent advances in endoscopie endonasal surgery have allowed for some of these tumors to be treated endoscopically. The purpose of this study was to assess the outcomes and complications of the endoscopie approach in a series of patients with paranasal sinus malignancies. Methods: A retrospective chart review was performed of patients with sinonasal or skull base malignancies treated with endoscopie or endoscopic-assisted resections at a tertiary care institution from 2002 to 2010. Patient data were collected on symptoms, tumor type, operative technique, and postoperative course. Baseline risk factors, overall and disease-free survival data, and surgical outcomes were compared between the two groups. Results: Of the total 49 patients, 36 (73%) underwent an endoscopie approach and 13 (27%) underwent endoscopic- assisted approaches. Sarcomas (9 cases) were the most common tumor type, followed by squamous cell carcinoma (8), adenocarcinoma (8), and melanoma (7). The mean follow-up time for all patients was 3.58 years (range, 1.1 to 8.8 years). Surgical complications were more frequent with open approaches than with endoscopie approaches (23.1% versus 5.6%; p = 0.11). Medical complications were significantly more common with open approaches (38.5% versus 8.3%; p = 0.02). The disease-specific mortality rate was 8% (4 of 49). The local tumor recurrence rate was 16% (8 of 49). The 3-year disease-free survival rates were 86.8% in the endoscopie group and 67.7% in the open group (p = 0.047); however, the patients in the endoscopie group had lower T stages (p = 0.0068) and lower ASA scores (p = 0.03). Conclusions: Endoscopie approaches to the sinuses and skull base have become progressively more sophisticated with advances in skull base reconstruction, advances in surgical technique, and improvements in technology. This study demonstrates the relative safety and utility of the endoscopie approach for sinonasal and skull base malignancies. In carefully selected patients, endoscopie approaches demonstrate survival rates comparable to those of traditional surgery, and fewer perioperative complications. With appropriate planning and careful surgical decision-making, endoscopie surgery shows promise as a minimally invasive alternative in the treatment of sinonasal malignancies. [ABSTRACT FROM AUTHOR]

Background/Aims: Tuberculum sellae meningiomas (TSMs) are challenging tumors for surgical resection. Endoscopic endonasal (EE) approaches to these lesions have not been directly compared to open craniotomy in a controlled trial. Methods: We searched Medline and Embase online databases for English-language articles containing key words related to TSMs. Data were pooled, including 5 of our own patients reported here for the first time. Metaregression was used and a decision-analytical model was constructed to compare outcomes between open microsurgery and EE approaches. Results: The overall quality of life (QOL) was not significantly different between the approaches (p = 0.410); however, there were large differences in individual complication rates. The Monte Carlo simulation yielded an overall average QOL in craniotomy patients of 0.915 and in endoscopic patients of 0.952. Endoscopy had a higher CSF leak rate (26.8 vs. 3.5%, p < 0.001) but a lower rate of injury to the optic apparatus (1.4 vs. 9.2%, p < 0.001) compared with craniotomy. The 3-year recurrence rates were not statistically different (p = 0.529). Conclusion: EE resection of TSMs appears to be a comparable alternative to traditional open microsurgical resection with respect to overall QOL based on available publications. A meaningful comparison of recurrence rates will require a longer follow-up. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinona-sal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimu-lation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection. [ABSTRACT FROM AUTHOR]

Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and coculture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS. [ABSTRACT FROM AUTHOR]

Aims: Survey the clinical symptoms, radiological features, management, and long-term outcomes of sinonasal and anterior skull base schwannomas. Patients and Methods: Retrospective review of patients with sinonasal schwannomas treated from June 2001 through January 2010 at two academic institutions. Results: There were 4 women and 3 men in this study. The mean age was 46 years (range 17-68). The mean tumor size was 2.4 cm (range 1.4-3.8 cm). Tumor locations included ethmoid sinuses (3), nasal cavity (2) and pterygopalatine fossa (2). Six patients had endoscopic resections, while 1 was approached and resected via a lateral rhinotomy. The mean follow-up was 2.8 years. There were no tumor recurrences during the study period. Conclusions: Schwannomas of the paranasal sinuses and nasal cavity are uncommon tumors that can usually present with vague and nonspecific symptoms. Magnetic resonance imaging can suggest the diagnosis; however, a definitive diagnosis is made by correlation with histopathological findings. Treatment is complete surgical resection. This study illustrates the effectiveness of the endoscopic endonasal approach in the treatment of these benign tumors. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purely endoscopic resections of transcranial/intracranial pathology represent an exciting minimally invasive option for some patients. There is an abundance of literature on surgical techniques, though very little deals with perioperative management, which is critical for good outcomes. We present a detailed case review and a perioperative management protocol with specific reference to skull base and neuroanatomy. We performed a retrospective chart review and analysis of outcomes and complications by approach and design and prospective employment of a perioperative management protocol in a major tertiary care referral hospital. We included patients undergoing endoscopic skull base approaches by the two senior surgeons from September 2005 to April 2009, selecting of transcranial/intracranial cases for detailed review. Our main outcome measures included perioperative morbidity, mortality, and complications; degree of resection; recurrence rate; and survival. Fifteen patients met study criteria. No perioperative mortality occurred. There were two major and four minor complications. Mean follow-up was 15 months; 11/13 patients with malignancies had no evidence of disease. A perioperative management protocol was designed from these data and has resulted in decreased lumbar drainage and increased fluid/electrolyte monitoring. Endoscopic transcranial/intracranial anterior skull base surgery is both safe and effective when a complete understanding of the surgery and perioperative management is achieved. [ABSTRACT FROM AUTHOR]

Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than nonsmokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition. [ABSTRACT FROM AUTHOR]

Background: Violation of the integrity of the airway (pulmonary parenchymal air leak or tracheobronchial injury) remains a challenging problem in chest medicine and thoracic surgery. Tissue sealants such as fibrin glue have been suggested to improve outcomes but they are still associated with significant failure rates. Laser tissue welding (LTW) is an alternative method that produces wound repairs that are significantly stronger than those of fibrin glue and may be used to repair air leaks.Methods: We used an Institutional Animal Care and Use Committees-approved New Zealand white rabbit model of lung parenchymal and tracheal injury. Lung wounds (n = 8 per condition) were created and either left open or repaired using fibrin glue or LTW. Tracheal wounds (n = 5 per condition) were created using incisions in the membranous and cartilaginous portions or by removing a tracheal ring, and were repaired using LTW. Within each tissue type, the burst strength of the wounds was measured using a digital manometer and were compared with one another using a two-tailed, paired Student t test.Results: Among the lung injuries, the burst strength of the LTW repair (19.95 +/- 4.98 mm Hg) was significantly stronger than that of the fibrin glue repair or open wound (10.53 +/- 5.01 mm Hg, P = .001, and 7.61 +/- 2.64 mm Hg, P < .001, respectively). Among the tracheal injuries, the burst strength of the membranous incision (101.00 +/- 20.25 mm Hg) was significantly higher than that of the cartilaginous incision (75.08 +/- 10.50 mm Hg, P = .03) but not that of the cartilaginous defect (77.34 +/- 12.35 mm Hg).Conclusions: LTW is capable of sealing wounds in the tracheobronchial tree and can produce bonds that are twice as strong as fibrin glue in lung parenchyma. LTW may be a better alternative than fibrin glue in the repair of injuries to the airway. [ABSTRACT FROM AUTHOR]

The article presents research which analyzed the use of laser tissue welding (LTW) in tracheobronchial and lung repair. The researchers used a white rabbit model of tracheal injury and lung parenchymal to measure the burst strength of the tracheal and lung wounds. They found that the burst strength of fibrin glue repair is weaker than the LTW repair.

Ecthyma gangrenosum is a rare necrotizing cutaneous infection usually caused by Pseudomonas aeruginosa. We report a case of ecthyma gangrenosum presenting as a sinonasal eschar and mimicking acute invasive fungal sinusitis in an immunocompromised 39-year-old man with a hematologic malignancy. To the best of our knowledge, this represents the fi rst case of ecthyma gangrenosum affecting the sinonasal mucosa to be reported in the literature. [ABSTRACT FROM AUTHOR]

Ecthyma gangrenosum is a rare necrotizing cutaneous infection usually caused by Pseudomonas aeruginosa. We report a case of ecthyma gangrenosum presenting as a sinonasal eschar and mimicking acute invasive fungal sinusitis in an immunocompromised 39-year-old man with a hematologic malignancy. To the best of our knowledge, this represents the first case of ecthyma gangrenosum affecting the sinonasal mucosa to be reported in the literature. [ABSTRACT FROM AUTHOR]

Tension pneumocephalus is a rare complication of functional endoscopic sinus surgery that may lead to rapid neurologic deterioration. Patients typically display symptoms within hours after the operation, and computed tomography reveals the presence of a skull base defect. We report a unique case of subacute tension pneumocephalus with no obvious skull base defect, which was associated with a pupil-involving third-nerve palsy. We discuss management of this complication and preventive measures for avoiding pneumocephalus after functional endoscopic sinus surgery. [ABSTRACT FROM AUTHOR]

This case video demonstrates a multidisciplinary approach to resection of a juvenile nasopharyngeal angiofibroma highlighting direct intratumoral onyx embolization. The patient is a 14-year-old boy who presented with a 1-month history of worsening epistaxis and nasal congestion. Preoperative magnetic resonance imaging demonstrated a 4.5 x 3 x 3 cm lobulated mass in the right pterygomaxillary space, sphenoid, and the nasopharynx adjacent to the cavernous carotid. Given the high vascularity of the lesion, intratumoral onyx embolization was undertaken, which significantly reduced intraoperative blood loss in this case. The present video demonstrates the technique for safe direct intratumoral onyx embolization and its role in significantly reducing intraoperative blood loss (Video 1). Postoperatively, the patient made an uncomplicated recovery. The patient consented to the procedure. [ABSTRACT FROM AUTHOR]