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Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration–approved for the most common form, CRS without nasal polyps (also called “chronic sinusitis”). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays.

The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well studied. We quantified long‐term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ESBS. Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to 2019. Data on patient demographics and postoperative treatment with nasal saline irrigation twice daily with and without dissolved steroids (mometasone or budesonide) was collected. Preoperative, and 1‐, 3‐, 6‐, 12‐, 18‐, and 24‐month postoperative Sino‐Nasal Outcome Test (SNOT‐22) scores were assessed. A total of 727 patients were assessed (53.4% males), with 479 patients in the no SI group and 248 patients in the SI group. Preoperative SNOT‐22 scores did not differ significantly (P= 0.19). 1‐, 3‐, 6‐, 12‐, 18‐, and 24‐month post‐op SNOT‐22 scores did not significantly differ between groups. However, mometasone irrigations resulted in significantly lower postoperative 2‐year SNOT‐22 scores compared to budesonide (P< 0.01) and saline (P= 0.03). Though corticosteroid irrigations are routine in managing inflammatory sinus disease, their role in postoperative management after ESBS for tumors is unclear. Our findings suggest that mometasone irrigation may be effective at improving postoperative quality of life in patients after ESBS.

Functional endoscopic sinus surgery is a commonly performed otolaryngologic procedure that often uses the microdebrider device for tissue removal. Given the ubiquitous nature of the instrument, we sought to better define the patterns of device failure using the postmarket surveillance openFDA database. The openFDA database was queried for all microdebrider‐related adverse events from January 1, 2000 to November 1, 2020. Descriptive information on the nature of device failure and any associated patient injury was compiled. Reports not directly related to device failure were excluded from the analysis. A total of 641 events were included in the analysis. The most common device failure was overheating (n= 348, 54.3%), followed by material separation (n= 173, 27%), and inconsistent device activation (n= 52, 8.1%). Of the reported events, the vast majority did not result in patient harm (n= 579, 90.3%). On review of the remaining cases, only 24 events (3.7%) resulted in true harm to the patient, defined as a temporary or permanent injury or >30 min of additional anesthesia time. Of these cases, the need to reschedule surgical cases (n= 5, 0.8%), retained foreign body (n= 5, 0.8%), and thermal tissue injury (n= 3,0.5%) were the most common. Five patients suffered an injury due to surgeon error unrelated to device malfunction (n= 5, 0.8%). Microdebrider device failures are extremely rare. When they do occur, less than 10% result in patient harm. In cases of patient harm related to microdebrider failure, preoperative testing of the device before use could prevent many of the reported malfunctions. The openFDA database was queried for adverse events related to microdebrider use over a 20‐year period.Analysis of the openFDA database demonstrates that microdebrider device failures are rare, and in over 90% of cases do not result in patient harm.The most common reasons for microdebrider device failure are overheating and device separation, and are likely related to component wear after repeated use or improper maintenance. The openFDA database was queried for adverse events related to microdebrider use over a 20‐year period. Analysis of the openFDA database demonstrates that microdebrider device failures are rare, and in over 90% of cases do not result in patient harm. The most common reasons for microdebrider device failure are overheating and device separation, and are likely related to component wear after repeated use or improper maintenance.

Carcinosarcomas are rare, aggressive malignancies that can arise in the nasal cavity and paranasal sinuses. There are limited outcome data available. Accordingly, we sought to use the National Cancer Database (NCDB) to characterize patient demographics and outcomes. A retrospective analysis of the NCDB from 2004 to 2016 for patients with sinonasal carcinosarcoma was conducted. Thirty patients were included. The patients were predominantly male (n= 20), white (n= 23), and privately insured (n= 15), with an average age of 62.4 years. The nasal cavity was the most common subsite (n= 14), followed by the maxillary sinus (n= 8). Most patient were treated with surgery followed by radiation (n= 23), with the remaining undergoing surgery alone (n= 4), radiation alone (n= 2), or no treatment (n= 1). One‐third (n= 10) received adjuvant chemotherapy. The 1‐ and 5‐year overall survival (OS) in the cohort were 79.2% and 43.3%, respectively. Univariate log‐rank testing showed OS varied based on intervention (P< 0.029), sex (P< 0.042), and age (P< 0.025), while on multivariate analysis none of these factors independently predicted OS. We describe the demographics and presenting features of a national cohort of sinonasal carcinosarcoma patients. Future research is needed to identify predictors of overall survival, and to assess the optimal roles for radiation and systemic chemotherapy. The demographics and outcomes for a cohort of 30 patients with sinonasal carcinosarcoma were described.Seventy‐six percent of patients were treated with surgery followed by adjuvant radiotherapy.1‐ and 5‐year survival from the time of diagnosis were 79.2% and 43.3% respectively.Neither surgical intervention, patient sex, nor patient age independently predicted survival outcomes. The demographics and outcomes for a cohort of 30 patients with sinonasal carcinosarcoma were described. Seventy‐six percent of patients were treated with surgery followed by adjuvant radiotherapy. 1‐ and 5‐year survival from the time of diagnosis were 79.2% and 43.3% respectively. Neither surgical intervention, patient sex, nor patient age independently predicted survival outcomes.

Objective To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach.Methods All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index.Results Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group (P= .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach (P= .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 (P= .411).Conclusions The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

Objectives Myoepithelial carcinoma (MECA) is a rare salivary gland tumor that can occur in the sinonasal cavity with poor outcomes. There are limited data on sinonasal outcomes to guide management. We sought to use the National Cancer Database (NCDB) to better define treatment outcomes in MECA.Methods We conducted a retrospective analysis of the NCDB from 2004 to 2016 for patients with MECA of the sinonasal cavity. Patient demographic, treatment, and survival information were extracted from the database. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival (OS).Results A total of 38 patients were included. The average age was 60.7 ± 18.2 years and male patients represented 47.4% of the cohort. Most patients were White (n = 26, 68.4%) and the majority of patients had either private insurance (n = 20, 52.6%) or Medicare (n = 15, 39.5%). The primary site of most tumors was nasal cavity (n = 19, 50%), followed by maxillary sinus (n = 16, 42.1%). Most tumors were >4 cm (n = 17, 44.7%). The 1-, 5-, and 10-year OS was 89.7% (95% confidence interval [CI]: 80.7%−99.8%), 63.6% (95% CI: 49.4%−82%), and 46.4% (95% CI: 31%−69.5%), respectively. The median survival for the overall cohort was 85.8 months. Medicare insurance was associated with a decreased OS (hazard ratio [HR]: 8.2; 95% CI: 2.88−23.4, P< .001). Patients who underwent surgery had a significant survival benefit (HR: 0.04, 95% CI: 0.01−0.21, P< .001).Discussion MECA of the sinonasal cavity is a rare tumor with poorly understood behavior. Data from the NCDB suggests that it is a relatively aggressive tumor with surgical management associated with better outcomes. This analysis is limited by the small sample size and further research into optimal treatment regimens is needed.

Objective: To determine in-hospital costs associated with performing an EEA to anterior skull base pathology and to identify drivers of cost variability for patients undergoing endoscopic anterior skull base surgery.Methods: All endoscopic anterior skull base surgeries performed over a period from January 1st, 2015 to October 24th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using Stata software.Results: An EEA was associated with an average total in-hospital cost of $44 545. Compared to patients undergoing a transsphenoidal approach to pituitary tumor resection, EEA patients incurred higher in-hospital costs across all variables including a total cost increase of $15 921 (95% confidence interval $5720-26 122, P= .002). Univariate analysis of all endoscopic anterior skull base surgery patients showed a cost increase of $30 616 associated with post-operative cerebrospinal fluid (CSF) leak ($10 420-50 811, P= .004), $14 610 with post-operative diabetes insipidus (DI) ($4610-24 609, P= .004), and $11 522 with African-American patients relative to Caucasian patients ($3049-19 995, P= .008).Conclusions: Patients who undergo endoscopic EEA for resection of anterior skull base tumors typically incur greater in-hospital costs than patients undergoing a standard TSA. Post-operative complications such as CSF leak and DI, as well as ethnicity, are significant drivers of cost-variability.

Background Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized.Objective To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases.Methods A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed.Results Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization.Conclusion ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected.

Background Acinic cell carcinoma (ACC) is a salivary gland malignancy that rarely can involve the sinonasal cavity. There are limited outcomes data available to guide management.Objective We sought to use the National Cancer Database (NCDB) to characterize treatment outcomes in sinonasal ACC.Methods A retrospective analysis of the NCDB from 2004 to 2016 for patients with ACC involving the sinonasal cavity was conducted. Demographic, treatment, and survival information were obtained. Unadjusted Kaplan-Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival (OS).Results A total of 28 patients were included in the analysis with an average age of 58.6 ± 15.5 years. Half the patients (n = 14, 50%) were male, mostly white (n = 23, 82.1%), and with private insurance (n = 16, 57.1%). The nasal cavity was the most common subsite (n = 18, 64.3%), followed by the maxillary sinus (n = 5, 17.9%). Most patient received surgery alone (n = 17, 60.7%), with the remaining patients undergoing surgery followed by radiation (n = 8, 28.6%), radiation alone (n = 1, 3.6%), and no treatment (n = 2, 7.1%). The 1-, 5-, and 10-year survival in this cohort was 100% (95% CI: 100%–100%), 84.3% (95% CI: 71.2%–99.7%), and 72.2% (95% CI: 55%–94.8%), respectively. On multivariate analysis, older age was associated with worse OS (hazard ratio (HR): 1.27; 95% CI: 1.11–1.46, P< .001). Disease of the sphenoid sinus correlated with worse survival (HR: 198, 95% CI: 10.4–3,739, P< .001) and large tumor size was associated with worse OS on log-rank test, but not on multivariate analysis.Conclusion Sinonasal ACC is a rare entity with relatively good long-term outcomes. Older age and primary disease of the sphenoid sinus are associated with worse outcomes. Most patients are treated with surgical resection. Future research is needed to assess the optimal timing and indications for radiation therapy.

Lesions of the pituitary and sellar region in children comprise a wide variety of pathologic conditions, but advances in surgical technology and techniques have enabled both biopsy and resection of such lesions despite age-dependent anatomic constraints. In this article, the authors discuss the common pathologic conditions encountered, perioperative management of these patients, surgical techniques required to address these lesions and repair the pediatric skull base, points of controversy, and future areas of work.

Background Aspirin-exacerbated respiratory disease (AERD) is optimally managed by endoscopic sinus surgery (ESS) followed by aspirin therapy after desensitization (ATAD). Most AERD quality of life (QOL) studies use the 22-item Sinonasal Outcomes Test (SNOT-22), which focuses predominantly on sinonasal outcomes.Objective This study seeks to assess QOL outcomes in AERD patients after ESS and ATAD via the 12-item Short Form Survey (SF-12), a well-validated QOL measure for general health status of chronic conditions.Methods Retrospective review of 112 AERD patients who underwent ESS followed by ATAD at our institution between 2016 and 2019. SF-12 was collected preoperatively, postoperatively/pre-AD, and serially post-AD (1–3, 4–6, 7–12, and >12?months). Optum® PRO CoRE software was used to compare data to national norms. ANOVA was performed comparing physical component summary (PCS), mental component summary (MCS) and eight health domains (physical functioning, role physical, general health, bodily pain, vitality, social functioning, role emotional, and mental health).Results AERD patients showed improvement in PCS scores across all timepoints after ESS and ATAD (p?=?0.004). When stratified by gender, women demonstrated an improvement in PCS scores (p?=?0.004). Within the domains, there were significant improvements in social functioning (SF), role physical (RP), and bodily pain (BP) at all timepoints (SF: p?=?0.006; RP: p?=?0.005; BP: p?

Background: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient’s forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system.Methods: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies.Results: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU.Conclusion: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.

Odontogenic sinusitis (ODS) is a common cause of orbital, intracranial, and osseous infectious extrasinus complications. Dental infections can spread to the orbital or intracranial spaces though the sinuses via thrombophlebitis or direct extension, or from the dentition or oral cavity via vascular channels in the maxillary alveolar bone. ODS typically presents with unilateral involvement both clinically and radiographically. Any suspicion for extrasinus spread based on history and physical exam should be followed by appropriate imaging, formal dental evaluation, and, when appropriate, ophthalmology and neurosurgery consultations. This multidisciplinary approach ensures appropriate management of both the acute orbital and intracranial complications, as well as the infectious dental and sinus pathologies.

The introduction of the vascularized pedicled nasoseptal flap has revolutionized endoscopic skull base surgery, providing a highly versatile option to repair even the most complex skull base defects. Though demonstrated with outstanding results in adult patients, there is limited experience in the pediatric population. Early investigation found that there are limitations in utilization of the nasoseptal flap in children due to craniofacial restrictions. More recently, these concerns have been mitigated, and nasoseptal flaps are reliably used in reconstructing even the largest skull base defects in the youngest patients. Preoperative planning and review of imaging and meticulous intraoperative dissection are essential for successful reconstructive outcomes. [ABSTRACT FROM AUTHOR]

With increasing adoption of endoscopic techniques and improved knowledge of skull base anatomy and approaches, transsphenoidal pituitary surgery is now being performed on patients of all ages. Surgical principles are similar between pediatric and adult patients, but there are special considerations for the pediatric population in terms of instrumentation, surgical anatomy, and postoperative care. Wide exposure to the sella, oftentimes to accommodate multiple instruments and the endoscope, is frequently necessary. Persistent collaboration among the otolaryngology, neurosurgery, and anesthesiology teams is of critical importance to ensure optimal outcomes. [ABSTRACT FROM AUTHOR]

Background Upper airway epithelial cells produce bactericidal nitric oxide (NO) in response to both gram-positive and gram-negative bacteria. Our previous work demonstrated that T2R38, a bitter taste receptor (T2R) expressed in airway epithelium, produces NO in response to quorum-sensing molecules secreted by Pseudomonas aeruginosa. We also demonstrated that Staphylococci products elicit an NO response when using a T2R-independent pathway. When screening additional human pathogens for epithelial T2R activation, we found that the gram-positive aerobe Bacillus cereus secretes a T2R agonist that yields NO production.Objective The objective of this study was to characterize the activating B. cereus product(s) and to describe the epithelial cell signaling pathway involved.Methods Sinonasal air-liquid interface cultures were treated with B. cereus conditioned medium (CM), and NO production was measured by using 4-amino-5-methylamino-2′,7′ -difluorofluorescein fluorescence imaging. Ciliary beat frequency (CBF) was assessed in response to B. cereus CM. Pharmacologic studies that use inhibitors of the T2R-signaling pathway were used to determine if the production of NO was mediated by a T2R. Purification studies were performed to analyze the physical properties of the activating product(s) contained in the CM.Results A product(s) secreted by B. cereus induced NO production and increased CBF. The response varied markedly between individual patients and involved two important components of bitter taste signaling, phospholipase C isoform β-2 and the transient receptor potential melastatin isoform 5 ion channel.Conclusions This study demonstrated that a B. cereus product(s) elicited an NO-mediated innate defense response in upper airway epithelium that seemed to be partially mediated by a T2R signaling pathway. The active product that elicited the NO response was likely a small nonpeptide compound, but further purification is required for identification. Patient variation in the NO response to B. cereus products could potentially be due to genetic differences in T2Rs.

Background Bitter taste receptors (T2R) have recently been demonstrated to contribute to sinonasal innate immunity. One T2R, T2R38, regulates mucosal defense against gram-negative organisms through nitric oxide (NO) production, which enhances mucociliary clearance and directly kills bacteria. To determine whether additional T2Rs contribute to this innate defense, we evaluated two other sinonasal T2Rs (T2R4 and T2R16) for regulation of NO production and expression within the human sinonasal cavity.Methods Primary human sinonasal cultures were stimulated with ligands specific to T2R4 and T2R16, colchicine and D-salicin, respectively. Cellular NO production was measured by intracellular 4-amino-5-methylamino-2’, 7′-difluorofluorescein diacetate fluorescence. For T2R expression mapping, sinonasal tissue was obtained from patients who underwent sinus surgery of the middle turbinate, maxillary sinus, ethmoid sinus, or sphenoid sinus. The expression of T2R4, T2R16, and T2R38 was evaluated by using immunofluorescence with validated antibodies.Results Similar to T2R38, T2R4 and T2R16 trigger NO production in a dose-dependent manner by using the canonical taste signaling pathway in response to stimulation with their respective ligands. All three receptors were expressed in the cilia of human epithelial cells of all regions in the sinonasal cavity.Conclusion These three T2Rs signaled through the same NO-mediated antimicrobial pathway and were ubiquitously expressed in the sinonasal epithelium. Additional T2Rs besides T2R38 may play a role in sinonasal immune defense. Mapping of T2R expression demonstrated the potential widespread role of T2Rs in sinonasal defense, whereas the genetics of these T2Rs may contribute to our understanding of specific endotypes of chronic rhinosinusitis and develop into novel therapeutic targets.

ABSTRACTApproximately 20% of the population is persistently colonized by Staphylococcus aureusin the nares. Th17-like immune responses mediated by the interleukin-17 (IL-17) family of cytokines and neutrophils are becoming recognized as relevant host defense mechanisms for resolution of S. aureusmucocutaneous infections. Since antimicrobial peptides are regulated by the IL-17 cytokines, we sought to determine the role of IL-17 cytokines in production of antimicrobial peptides in a murine model of S. aureusnasal carriage. We discovered that nasal tissue supernatants have antistaphylococcal activity, and mice deficient in both IL-17A and IL-17F lost the ability to clear S. aureusnasal colonization. IL-17A was found to be sufficient for nasal mBD-3 production ex vivoand was required for CRAMP, mBD-3, and mBD-14 expression in response to S. aureuscolonization in vivo. These data were confirmed in a clinical study of nasal secretions in which elevated levels of the human forms of these antimicrobial peptides were found in nasal secretions from healthy human subjects when they were colonized with S. aureusbut not in secretions from noncolonized subjects. Together, these data provide evidence for the importance of IL-17A regulation of antimicrobial peptides and IL-17F in the clearance of S. aureusnasal carriage.

Frontal recess dissection proposes many challenges to the surgeon. These challenges stem from its highly variable nature, small caliber, difficult visualization, and proximity to vital structures such as the skull base and orbit. As such, delicate mucosal-sparing dissection of the frontal recess with proper instrumentation is paramount to minimize scar formation and ensure patency. Here, the article explores key instrumentation in frontal recess surgery with an emphasis on hand instruments and adjunctive technologies.

Background Endoscopic endonasal repair of cerebrospinal fluid (CSF) rhinorrhea secondary to idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri or benign intracranial hypertension, has varying success rates, from 25–87%, with minimal morbidity. However, often these series have a relatively short-term follow-up. Given the pathophysiology of IIH, long-term follow-up is necessary to identify true CSF leak recurrence rates. Our investigation aimed to evaluate long-term outcomes in endoscopically repaired CSF leaks.Methods A retrospective chart review of all the patients with CSF rhinorrhea due to IIH who met inclusion criteria between 1996 and 2009. Outcome measures included the following: demographics, intracranial pressure, location of skull base defect, presence of encephalocele and/or meningoencephalocele, surgical repair technique, treatment with acetazolamide, whether a ventriculoperitoneal shunt was inserted, location of recurrence, history of meningitis or previous sinus surgery, and duration of follow-up.Results Thirty-two patients with a total of 44 skull base defects were reviewed over a mean follow-up of 10.2 years. The mean body mass index and intracranial pressure were 36.8 kg/m2and 27.7 cm H2O, respectively. Seven patients (18%) required revision surgery at the same site or a distant site. We found no statistical significance that identified the recurrence risk in the outcome measurements most likely due to our small failure rate. However, early recurrences were noted to recur at the same repair site, whereas late recurrences were noted to recur at a distant site along the skull base.Conclusion IIH is an increasingly recognized entity treated by otorhinolaryngologists. We present the first long-term IIH CSF leak repair series. Long-term follow-up is necessary because delayed CSF leaks occur in this population.

Background T2R bitter taste receptors play a crucial role in sinonasal innate immunity by upregulating mucociliary clearance and nitric oxide (NO) production in response to bitter gram-negative quorum-sensing molecules in the airway surface liquid. Previous studies showed that phytochemical flavonoid metabolites, known as anthocyanidins, taste bitter and have antibacterial effects. Our objectives were to examine the effects of anthocyanidins on NO production by human sinonasal epithelial cells and ciliary beat frequency, and their impact on common sinonasal pathogens Pseudomonas aeruginosa and Staphylococcus aureus.Methods Ciliary beat frequency and NO production were measured by using digital imaging of differentiated air-liquid interface cultures prepared from primary human cells isolated from residual surgical material. Plate-based assays were used to determine the effects of anthocyanidins on bacterial swimming and swarming motility. Biofilm formation and planktonic growth were also assessed.Results Anthocyanidin compounds triggered epithelial cells to produce NO but not through T2R receptors. However, anthocyanidins did not impact ciliary beat frequency. Furthermore, they did not reduce biofilm formation or planktonic growth of P. aeruginosa. In S. aureus, they did not reduce planktonic growth, and only one compound had minimal antibiofilm effects. The anthocyanidin delphinidin and anthocyanin keracyanin were found to promote bacterial swimming, whereas anthocyanidin cyanidin and flavonoid myricetin did not. No compounds that were tested inhibited bacterial swarming.Conclusion Results of this study indicated that, although anthocyanidins may elicited an innate immune NO response from human cells, they do not cause an increase in ciliary beating and they may also cause a pathogenicity-enhancing effect in P. aeruginosa. Additional studies are necessary to understand how this would affect the use of anthocyanidins as therapeutics. This study emphasized the usefulness of in vitro screening of candidate compounds against multiple parameters of both epithelial and bacterial physiologies to prioritize candidates for in vivo therapeutic testing.

Introduction Cerebrospinal fluid (CSF) leak occurs in 1-11% of endoscopic Draf III, or endoscopic modified Lothrop, procedures. CSF leak can occur during surgery during a superior nasal septectomy. This study investigated whether the posterior edge of the nasofrontal beak (NFB) at the level of the internal frontal ostium is a safe landmark to use to avoid skull base injury when beginning the superior septectomy.Methods Preoperative computed tomography maxillofacial scans were reviewed from 100 patients from the University of Pennsylvania sinus surgery data base. The narrowest anteroposterior distance between the posterior edge of the NFB and the anterior aspect of the olfactory fossa (OF) at the level of the internal frontal ostium was measured in each patient. Measurements were taken in the midline and to the left and right of midline. Six fresh cadaver heads were also dissected to evaluate these relationships.Results On computed tomography analysis, the NFB was anterior to the OF on the left and right of the midline in 100% of the patients, with mean distances of 6.04 and 6.41 mm, respectively. The NFB was anterior to the OF in the midline in 98% of patients, with a mean distance of 9.02 mm. In all six cadavers, the posterior edge of the NFB was anterior to the OF in the midline and to the left and right of midline at the level of the internal frontal ostia.Conclusions During Draf III, the posterior edge of the NFB was a reliable landmark for avoiding iatrogenic CSF leak during the superior septectomy.