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Background: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6‐item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS. The purpose of this multicenter study was to determine the incidence of patients with ENS6Q ≥ 11 following subtotal MTR during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing preoperative and postoperative ENS6Q scores. Methods: A multi‐institutional prospective cohort study (8 US institutions) was conducted on patients who underwent bilateral subtotal MTR during ESS for CRSwNP. Preoperative and postoperative ENS6Q scores were compared after at least 12 months of postoperative follow‐up. Results: Of 110 patients, mean age was 51.6 years and 59.1% were male. Mean follow‐up was 14.5 ± 2.5 months (range 12.1–22.3 months). Mean preoperative and postoperative ENS6Q were 7.7 and 2.2, respectively, demonstrating a mean 5.5 point decrease postoperatively (p < 0.0001). At final follow‐up, no patient had an ENS6Q ≥ 11. Of note, 20% of patients had preoperative ENS6Q scores ≥11, but all decreased to <11 postoperatively. Conclusions: Based on prospective multicenter data over 1–2 years postoperatively, subtotal MTR for CRSwNP never led to ENS6Q scores ≥11, and patients experienced significant decreases in ENS6Q postoperatively. Subtotal MTR during ESS for CRSwNP was, therefore, unlikely to cause ENS even with long‐term follow‐up. Level of Evidence: 4 Laryngoscope, 135:59–65, 2025 [ABSTRACT FROM AUTHOR]

Objectives: Previously, we developed a novel double‐coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. Methods: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release. Results: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (μm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side. Conclusion: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model. Level of Evidence: N/A Laryngoscope, 134:3953–3959, 2024 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The periorbital suspension (PS) is an advanced adjunctive technique performed during endoscopic approaches to frontal sinus pathology that would be too far lateral or superior to address using traditional endoscopic transnasal approaches. The objectives of this study are to characterize the utility of this technique for frontal sinus pathology, determine anatomic limitations, and assess clinical outcomes following surgical treatment. Study Design: Prospective case series. Methods: Patient data including demographics, etiology, technique, complications, and clinical follow‐up were collected. Preoperative computed tomography scans were reviewed for maximum lateral and superior extent of pathology, supraorbital recess height, anterio‐posterior (AP) diameter of the frontal sinus, interorbital distance, and orbital—first olfactory neuron distance. Results: The PS approach was used in 30 surgeries (29 patients) for cerebrospinal fluid leaks (n = 5), benign tumors (n = 17), malignant tumors (n = 5), allergic fungal sinusitis (n = 2), and mucocele (n = 1) between 2018 and 2020. Approaches included 15 Draf IIB and 15 Draf III frontal sinusotomies. All pathology was surgically accessible using the PS approach and there were no intraoperative or postoperative complications. Postoperative follow‐up was 11.7 ± 7.6 months. Mean recorded measurements (in mm) were as follows: maximum lateral extent −15.0 ± 7.7, superior extent 21.2 ± 7.7 in surgical plane and 20.9 ± 9.8 in the vertical plane, supraorbital recess height −2.6 ± 1.9, AP frontal sinus diameter −13.2 ± 4.7, interorbital distance −29.8 ± 5.4, and orbital‐olfactory neuron distance −14.8 ± 2.9. Conclusions: The PS technique can be safely and successfully utilized to provide endoscopic endonasal access to lateral and superior frontal sinus pathology. Level of Evidence: 4 Laryngoscope, 132:538–544, 2022 [ABSTRACT FROM AUTHOR]

Objective: Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks. Methods: Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short‐term success of skull base repair, complications, hospital length of stay, and cost‐based analysis. Results: Fifty‐five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P =.90). Postoperative complications (3.6% vs. 7.4%; P =.53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P =.41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P =.14) or recurrent leak (7.1% vs. 0%; P =.16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P <.01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P =.18). Conclusion: An expedited monitoring protocol shortened hospital stay without increased risk of complications. Level of Evidence: III Laryngoscope, 131:E408–E412, 2021 [ABSTRACT FROM AUTHOR]

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Objective: The objectives of the current experiments were to develop and characterize primary rat nasal epithelial cultures and evaluate their usefulness as a model of cystic fibrosis (CF) sinonasal transepithelial transport and CF transmembrane conductance regulator (CFTR) function.Study Design: Laboratory in vitro and animal studies.Methods: CFTR+/+ and CFTR-/- rat nasal septal epithelia (RNSE) were cultured on semipermeable supports at an air-liquid interface to confluence and full differentiation. Monolayers were mounted in Ussing chambers for pharmacologic manipulation of ion transport and compared to similar filters containing murine (MNSE) and human (HSNE) epithelia. Histology and scanning electron microscopy (SEM) were completed. Real-time polymerase chain reaction of CFTR+/+ RNSE, MNSE, and HSNE was performed to evaluate relative CFTR gene expression.Results: Forskolin-stimulated anion transport (ΔIsc in μA/cm2 ) was significantly greater in epithelia derived from CFTR+/+ when compared to CFTR-/- animals (100.9 ± 3.7 vs. 10.5 ± 0.9; P < 0.0001). Amiloride-sensitive ISC was equivalent (-42.3 ± 2.8 vs. -46.1 ± 2.3; P = 0.524). No inhibition of CFTR-mediated chloride (Cl- ) secretion was exhibited in CFTR-/- epithelia with the addition of the specific CFTR inhibitor, CFTRInh -172. However, calcium-activated Cl- secretion (UTP) was significantly increased in CFTR-/- RNSE (CFTR-/- -106.8 ± 1.6 vs. CFTR+/+ -32.2 ± 3.1; P < 0.0001). All responses were larger in RNSE when compared to CFTR+/+ and CFTR-/- (or F508del/F508del) murine and human cells (P < 0.0001). Scanning electron microscopy demonstrated 80% to 90% ciliation in all RNSE cultures. There was no evidence of infection in CFTR-/- rats at 4 months. CFTR expression was similar among species.Conclusion: The successful development of the CFTR-/- rat enables improved evaluation of CF sinus disease based on characteristic abnormalities of ion transport.Level Of Evidence: NA. Laryngoscope, 127:E384-E391, 2017. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Spontaneous cerebrospinal fluid (CSF) leaks are associated with increased intracranial pressure (ICP) and considered a manifestation of idiopathic intracranial hypertension. Although postoperative acetazolamide and placement of CSF shunt systems are considered valuable interventions for elevated ICP, the impact on recurrence rate remains unclear. The objective of this study was to systematically review evidence from reported literature to evaluate whether postoperative ICP management reduces recurrence rates after primary endoscopic repair.Study Design: Prospective case series and systematic review.Methods: Demographics, defect location, success rates, and ICP management in spontaneous CSF leak patients were prospectively collected over 8 years. A search was also conducted in PubMed to identify studies reporting cases of spontaneous CSF rhinorrhea.Results: Fifty-six articles with nonduplicated data were identified and combined with a prospective series of 108 patients for a total of 679 patients treated for spontaneous CSF rhinorrhea. Average age was 50.4 years with 77% female. Average body mass index was 35.8 kg/m2 . Defects were most commonly located in the sphenoid sinus (n = 334) followed by the ethmoid (n = 318) and the frontal sinus (n = 46). Successful primary repair was 92.82% in patient cohorts where ICP evaluation and intervention with acetazolamide or CSF shunt systems was performed, but was significantly decreased to 81.87% in series with no active management of elevated ICP (P < .001).Conclusions: Evaluation and intervention for elevated ICP in spontaneous CSF leaks is associated with significantly improved success rates following primary endoscopic repair.Level Of Evidence: 4. Laryngoscope, 127:2011-2016, 2017. [ABSTRACT FROM AUTHOR]

Objective/hypothesis: Ineffective mucociliary clearance (MCC) is a common pathophysiologic process that underlies airway inflammation and infection. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR). Decreased transepithelial Cl(-) transport secondary to an acquired CFTR deficiency may exacerbate respiratory epithelial dysfunction by diminishing MCC and increasing mucus viscosity. The objectives of the present study are to 1) develop a model of acquired CFTR deficiency in sinonasal epithelium using hypoxia, 2) investigate whether the polyphenol resveratrol promotes CFTR-mediated anion transport, 3) explore resveratrol mechanism of action and determine therapeutic suitability for overcoming acquired CFTR defects, and 4) test the drug in the hypoxic model of acquired CFTR deficiency in preparation for a clinical trial in human sinus disease. We hypothesize that hypoxia will induce depletion of airway surface liquid (ASL) secondary to acquired CFTR deficiency and that resveratrol will restore transepithelial Cl(-) secretion and recover ASL hydration.Study Design: Basic science.Methods: Murine nasal septal (MNSE) and human sinonasal epithelial (HSNE) cultures were incubated under hypoxic conditions (1% O2 , 5% CO2 ) and transepithelial ion transport (change in short-circuit current = ΔISC ) evaluated in Ussing chambers. Resveratrol was tested using primary cells and HEK293 cells expressing human CFTR by Ussing chamber and patch clamp techniques under both phosphorylating and nonphosphorylating conditions. CFTR activation was evaluated in human explants and by murine in vivo (nasal potential difference) assessment. Cellular cyclic adenosine monophosphate (cAMP) (ELISA) and subsequent CFTR regulatory domain (R-D) phosphorylation (gel-shift assay) were also evaluated. Effects of hypoxia and resveratrol on ASL were tested using confocal laser scanning microscopy (CLSM) and micro-optical coherence tomography (µOCT).Results: Hypoxia significantly decreased ΔISC (in µA/cm(2) ) attributable to CFTR at 12 and 24 hours of exposure in both MNSE (13.55 ± 0.46 [12 hours]; 12.75 ± 0.07 [24 hours] vs. 19.23 ± 0.18 [control]; P < 0.05) and HSNE (19.55 ± 0.56 [12 hours]; 17.67 ± 1.13 [24 hours] vs. 25.49 ± 1.48 [control]; P < 0.05). We have shown that resveratrol (100 μM) enhanced CFTR-dependent Cl(-) secretion in HSNE to an extent comparable to the recently Food and Drug Administration-approved CFTR potentiator, ivacaftor. Cl(-) transport across human sinonasal explants (78.42 ± 1.75 vs. 1.75 ± 1.5 [control]; P < 0.05) and in vivo murine nasal epithelium (-4 ± 1.8 vs. -0.8 ± 1.7 mV [control]; P < 0.05) were also significantly increased by the drug. No increase in cAMP or CFTR R-D phosphorylation was detected. Inside-out patches showed increased CFTR open probability (NPo/N (N = channel number]) compared to controls in both MNSE (0.329 ± 0.116 vs. 0.119 ± 0.059 [control]; P < 0.05) and HEK293 cells (0.22 ± 0.048 vs. 0.125 ± 0.07 [control]; P < 0.05). ASL thickness was decreased under hypoxic conditions when measured by CLSM (4.19 ± 0.44 vs. 6.88 ± 0.67 [control]; P < 0.05). A 30-minute apical application of resveratrol increased ASL depth in normal epithelium (8.08 ± 1.68 vs. 6.11 ± 0.47 [control]; P < 0.05). Furthermore, hypoxia-induced abnormalities of fluid and electrolyte secretion in sinonasal epithelium were restored with resveratrol treatment (5.55 ± 0.74 vs. 3.13 ± 0.17 [control]; P < 0.05).Conclusions: CFTR activation with a leading edge Cl(-) secretagogue such as resveratrol represents an innovative approach to overcoming acquired CFTR defects in sinus and nasal airway disease. This exciting new strategy bears further testing in non-CF individuals with chronic rhinosinusitis.Level Of Evidence: N/A. Laryngoscope, 125:S1-S13, 2015. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Endoscopic medial maxillectomy (EMM) has become the surgical procedure of choice for resection of maxillary sinus inverted papillomas (IPs). Traditionally, IPs pedicled on the anterior and/or lateral walls of the maxillary sinus have required an adjuvant Caldwell-Luc approach due to decreased visualization with transnasal endoscopy in these locations. The objective of the current study is to evaluate outcomes following endoscopic resection of anterolateral maxillary sinus IPs. Study Design Prospective case series. Subjects and Methods Over 6 years, a total of 35 patients underwent EMM for maxillary sinus IPs located on the anterolateral maxillary wall. Demographics, operative technique, pathology, complications, recurrence, and postoperative follow-up were evaluated. Results The majority of patients were male (71%) with a mean age of 56 years (range 27-83). Most patients (71%) were referred for recurrence after previous attempts at surgical resection. Adequate visualization was obtained following EMM in the majority of patients with use of a 70-degree endoscope and angled instrumentation. The addition of transseptal surgical access was critical to the removal of IPs in 16 patients. No Caldwell-Luc approaches were required. Pathologic dysplasia was identified in nine patients, and three had carcinoma. There were no recurrences with a mean disease-free interval of 29 months (10-72 months). Conclusion In the present study, EMM provided excellent surgical access to anterolateral maxillary sinus IPs. The transseptal approach allowed enhanced visualization to this challenging location, previously considered accessible only with external procedures. Level of Evidence 4. Laryngoscope, 125:807-812, 2015 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Surgical treatment of inverted papilloma (IP) of the sphenoid sinus is complicated by close proximity to vital structures of the skull base. Identifying the site of tumor attachment and achieving complete removal can be challenging compared to IP at other sites. The objective of this study is to illustrate the clinical presentation, management, and risk factors for tumor recurrence for sphenoid IP. Study Design Retrospective study. Methods A multi-institutional, retrospective review of endoscopic resections of IP based within the sphenoid sinus was performed from 1996 to 2014. Demographic and tumor data, operative notes, complications, and recurrence rates were collected. Statistical analysis was performed to identify risk factors for tumor recurrence. Results Forty-eight patients (31 males, 17 females) were identified. Mean age was 57 years, with a median follow-up of 13.6 months (range 6.8-36). Rate of tumor recurrence was 14.6%, with median time to recurrence of 13.1 months. Patients with dysplasia/carcinoma in situ (CIS) had a 3.6 greater rate of recurrence (RR) compared to patients with no dysplasia, approaching significance (RR = 3.6; P = 0.08). Patients with IP attachment sites overlying the optic nerve or carotid artery had a 4.76 greater rate of recurrence compared to other sites (RR = 4.76; P = 0.073). Conclusion Sphenoid sinus IP is associated with a 14.6% rate of recurrence after surgery. Potential risk factors for tumor recurrence identified in this study include attachment sites over the optic nerve and carotid artery or evidence of dysplasia or CIS. Close follow-up in the postoperative period is essential for these patients to monitor for tumor recurrence. Level of Evidence 4. Laryngoscope, 125:544-548, 2015 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Removal of the medial orbital wall for sinonasal tumor involvement is required to obtain complete oncologic resection. However, orbital fat herniation can produce significant morbidity, including enophthalmos and diplopia. The purpose of the current study was to evaluate outcomes following use of porcine small intestine submucosa (SIS) grafts for orbital reconstruction following extirpation of sinonasal malignancies. Study Design Case series in a tertiary hospital setting. Methods Review of prospectively collected data regarding orbital reconstruction using SIS was performed. Demographics, tumor histology, size of orbital defect, adjuvant treatment, clinical status, and complications were recorded. Results Seventeen patients (average age, 58 years; range, 27-82 years) had SIS grafting of the medial orbital wall over a 5-year period at our tertiary academic institution. The average orbital wall defect size was 4.6 cm2 (range, 1 cm2−24 cm2). Tumor histopathology included esthesioneuroblastoma (n = 5), squamous cell carcinoma (n = 4), adenocarcinoma (n = 2), sinonasal undifferentiated carcinoma (n = 2), melanoma (n = 3), and neuroendocrine carcinoma (n = 1). Surgical goals were curative intent in all patients. Ten patients had postoperative radiation therapy, whereas five individuals had surgical extirpation following neoadjuvant chemotherapy and radiation. All patients had complete locoregional control at last clinical follow-up (average, 16 months; range, 2-54 months), although three patients developed distant metastases. The only orbital complications noted were enophthalmos (n = 1), periorbital cellulitis (n = 1), and orbital wall crusting (n = 1). Conclusions SIS reconstruction of orbital wall defects was effective in the current series of patients, with only one patient developing noticeable enophthalmos and a low incidence of surgical complications. Level of Evidence 4. Laryngoscope, 124:E219-E223, 2014 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Mounting evidence indicates the majority of spontaneous cerebrospinal fluid (CSF) leaks are associated with intracranial hypertension. The objectives of the current study were to assess outcomes regarding spontaneous CSF leaks focusing on premorbid factors, surgical technique, and management of intracranial pressure. Study Design Prospective cohort. Methods Prospective evaluation of patients with spontaneous CSF leaks was performed. Data regarding demographics, nature of presentation, body mass index (BMI), location and size of defect, intracranial pressure, clinical follow-up, and complications were collected. Results Over 5 years, 46 patients (average age, 51 years) with 56 spontaneous CSF leaks were treated by a single otolaryngologist. Twenty-one subjects presented with recurrence of their CSF leak following previous endoscopic and/or open approaches by other physicians. Obesity was present in 78% of individuals (average BMI, 35.6). Fifty-two CSF leaks (93%) were successfully repaired at first attempt. With secondary repair, all CSF leaks were closed at last clinical follow-up (average, 93 weeks). Three patients developed late failures (>2 months), with one recurrence at a distinct location from the primary site at 8 months postprocedure (associated with ventriculoperitoneal shunt failure). Opening pressures via lumbar puncture averaged 24.3 ± 8.3 cm H20, which increased significantly to 32.3 ± 9.0 cm H20 ( P < .0001) following closure of the skull base defect(s). Management of intracranial hypertension included acetazolamide (n = 23) or permanent CSF diversion (n = 19, including five revisions of failed preexisting shunts). Conclusions Although spontaneous CSF leaks have the highest recurrence rate of any etiology, prospective evaluation demonstrates high success rates with control of intracranial hypertension. Level of Evidence 4. Laryngoscope, 124:70-75, 2014 [ABSTRACT FROM AUTHOR]

The article discusses simultaneous pericranial (PCF) and nasoseptal flaps (NSF) reconstruction of anterior skull base defects after endoscopic-assisted craniofacial resection. The materials and methods used in the surgery are explained. The article concludes that The combined PCF and NSF is a valid option for defects extending to the planum sphenoidale and may provide additional support when iatrogenic tears are encountered.

Objectives/Hypothesis: Evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature to chronic rhinosinusitis. Tobacco-smoke exposure is thought to inhibit transepithelial Cl− secretion, a major determinant of airway surface liquid hydration and MCC. The objective of the current study was to evaluate the effects of acrolein exposure (a prominent tobacco smoke toxin) on vectorial Cl− transport through the major apical anion channel cystic fibrosis transmembrane conductance regulator (CFTR) in sinonasal epithelium. Study Design: In vitro investigation. Methods: Primary murine nasal septal epithelia (MNSE; wild-type and transgenic CFTR−/−) cultures were exposed to acrolein in Ussing chambers and the effects on Cl− secretion investigated using pharmacologic manipulation. Cellular cyclic adenosine monophosphate (cAMP) signaling and cytotoxicity were also investigated. Results: Acrolein stimulated Cl− secretion (ΔISC-change in short-circuit current in μA/cm2) at concentrations similar to smoker's airways (100 μM, 15.8 ± 2.2 vs. 2.4 ± 0.8 [control]; P < .0001), suppressed forskolin-stimulated C− transport at 300 μM (13.3 ± 1.2 vs. 19.9 ± 1.0; P < .01), and completely abolished all transport at 500 μM (−1.1 ± 1.6). Stimulated Cl− secretion was solely reliant upon the presence of CFTR (confirmed in transgenic CFTR−/− MNSE), but independent of cAMP signaling. Inhibition at higher concentrations was not secondary to cellular cytotoxicity. Conclusions: The present study demonstrates that acrolein has complex but pronounced interaction with the major apical Cl− transport mechanism that uses CFTR. Further investigations are required to determine acrolein's impact as a tobacco smoke constituent on mucociliary transport. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Sinonasal respiratory epithelial mucociliary clearance is dependent on the transepithelial transport of ions such as Cl−. The objectives of the present study were to investigate the role of oxygen restriction in 1) Cl− transport across primary sinonasal epithelial monolayers, 2) expression of the apical Cl− channels cystic fibrosis transmembrane conductance regulator (CFTR) and transmembrane protein 16A (TMEM16A), and 3) the pathogenesis of chronic rhinosinusitis. Study Design: In vitro investigation. Methods: Murine nasal septal epithelial (MNSE), wild type, and human sinonasal epithelial (HSNE) cultures were incubated under hypoxic conditions (1% O2, 5% CO2). Cultures were mounted in Ussing chambers for ion transport measurements. CFTR and TMEM16A expression were measured using quantitative reverse-transcription polymerase chain reaction (RT-PCR). Results: The change in short-circuit current (ΔISC in microamperes per square centimeter) attributable to CFTR (forskolin-stimulated) was significantly decreased due to a 12-hour hypoxia exposure in both MNSE (13.55 ± 0.46 vs. 19.23 ± 0.18) and HSNE (19.55 ± 0.56 vs. 25.49 ± 1.48 [control]; P < .05). TMEM16A (uridine triphosphate-stimulated transport) was inhibited by 48 hours of hypoxic exposure in MNSE (15.92 ± 2.87 vs. 51.44 ± 3.71 [control]; P < .05) and by 12 hours of hypoxic exposure in HSNE (16.75 ± 0.68 vs. 24.15 ± 1.35 [control]). Quantitative RT-PCR (reported as relative mRNA levels ± standard deviation) demonstrated significant reductions in both CFTR and TMEM16A mRNA expression in MNSE and HSNE owing to airway epithelial hypoxia. Conclusions: Sinonasal epithelial CFTR and TMEM16A-mediated Cl− transport and mRNA expression were robustly decreased in an oxygen-restricted environment. These findings indicate that persistent hypoxia may lead to acquired defects in sinonasal Cl− transport in a fashion likely to confer mucociliary dysfunction in chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Objective/Hypothesis: Therapeutic agents that enhance mucociliary transport (via stimulation of transepithelial Cl secretion) and inhibit inflammation could provide considerable advantages over conventional treatments for chronic rhinosinusitis (CRS). The objectives of the present study were to investigate whether the polyphenolic compound resveratrol promotes transepithelial Cl- transport and inhibits KC/IL-8 secretion in sinonasal epithelium. Study Design: In vitro and in vivo study. Methods: Transepithelial Cl- transport was investigated in primary murine nasal septal (MNSE) and human sinonasal epithelial (HSNE) cultures. In vivo activity was also measured using the murine nasal potential difference assay. CFTR R-domain phosphorylation and cAMP levels were examined as a test of cAMP/PKA-dependent activation. In vitro LPS-induced KC/ IL-8 secretion was quantified and compared to a panel of intranasal steroids. Results: Resveratrol(100 lM) significantly increased CFTR-mediated Cl- transport (change in short-circuit current, DISC) in both MNSE (13.51 6 0.77 vs. 4.4 6 0.66 [control]; P < .05) and HSNE (12.28 6 1.08 vs. 0.69 6 0.32 [control]; P < .05).Cl- secretion across in vivo murine nasal epithelium was also enhanced (-4 6 1.8 vs. -0.8 6 1.7mV [control], P < .05). There was no increase in cellular cAMP or CFTR R-domain phosphorylation detected. Resveratrol also significantly inhibited KC/IL-8 secretion in a dose-dependent fashion (pg/mL) in MNSE (181 6 39[100 μM) vs. 94 6 16 [200 μM] vs. 16 6 22 [500 lM] vs. 1195 6 355 [LPS control]; P < .001). The compound robustly abrogated KC/IL-8 secretion when compared to ciclesonide (765 6 139), triamcinolone (561 6 124), and budesonide (742 6 428), but had similar activity to fluticasone proprionate (65 6 47). Similar effects were demonstrated in HSNE (975 6 244 [100 μM] vs. 1825 6 144 [LPS control]; P < .001) with inhibition comparable to fluticasone proprionate (785 6 277). Conclusions: These in vitro and in vivo findings indicate resveratrol is a potent Cl- secretagogue and anti-inflammatory agent. Future clinical trials for CRS are warranted. [ABSTRACT FROM AUTHOR]

Objectives: Numerous studies have demonstrated the efficacy and safety of endoscopic management of cerebral spinal fluid (CSF) rhinorrhea, encephaloceles, and anterior skull base defects. Techniques have evolved as new instrumentation has developed, but typically involve meticulous bipolar cautery to decrease the potential for intracranial bleeding. The present study evaluated the Coblator™ as a novel tool in transnasal endoscopic management of encephaloceles. Study Design: Outcomes study. Methods: A prospective cohort involving 19 patients with 22 encephaloceles (19 spontaneous, 3 traumatic) reduced with the Coblator™ (radiofrequency coblation plus bipolar modality) was compared to a retrospective cohort of six encephaloceles (five spontaneous, one traumatic) removed with endoscopic bipolar cautery. Main outcome measures included duration of encephalocele removal and bleeding events. Bleeding encountered during removal was considered a minor event unless more than one attempt at cauterization was required. Other data collected included standard demographics, encephalocele size, and complications. Results: Average duration of coblation-assisted encephalocele removal was 15.8 minutes compared to 46 minutes with standard bipolar cautery (P = .0003). Average number of bleeding episodes did not significantly differ between groups (Coblator™, 1.0 ± 1.57 vs. bipolar, 1.17 ± 0.98; P = .80). One episode of major bleeding occurred in the coblation group when an anterior ethmoid artery was encountered during removal. Encephalocele size was similar between groups (Coblator™, 17.4 mm vs. bipolar, 16.6 mm; P = .65). Conclusions: Radiofrequency coblation significantly increased intraoperative speed during encephalocele removal with similar hemostatic properties when compared to bipolar cautery alone and represents a useful instrument in the management of encephaloceles. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The cystic fibrosis transmembrane conductance regulator (CFTR) serves as a predominant Cl- transport conduit in airway epithelium and is inhibited by cigarette smoke in vitro and in vivo. Activation of secondary Cl- transport pathways through calcium-activated Cl- channels (CaCC) has been postulated as a mechanism to bypass defects in CFTR-mediated transport. Because it is not known whether CaCCs are also inhibited by tobacco exposure, the current study was designed to investigate the effect of cigarette smoke condensate (CSC) on CaCC transport. Study Design: In vitro study. Methods: Well-characterized primary murine nasal septal epithelial (MNSE) and human sinonasal epithelial (HSNE) cultures were exposed to CSC in Ussing chambers. We monitored CaCC short-circuit current through stimulation of P2Y purinergic receptors with uridine triphosphate or adenosine triphosphate and selective inhibition of the CFTR-dependent secretory pathway. Characterization of CaCC current was also accomplished in primary airway cells derived from transgenic CFTR-/- (knockout) murine models. Results: Change in CaCC-mediated current (ΔISC representing transepithelial Ca-mediated Cl- secretion in μA/cm2) was significantly decreased in CSC-exposed wild type MNSE when compared to controls (32.8 ± 4.6 vs. 47.5 ± 2.3; respectively; P < .02). A similar effect was demonstrated in CFTR-/- MNSE cultures (33.4 ± 2.8 vs. 38.6 ± 2.0; P < .05>. HSNE cultures also had a significant reduction in ISC (16.1 ± 0.6 vs. 22.7 ± 0; P = .008). Conclusions: CSC affects multiple pathways fundamental to airway ion transport, including both cyclic adenosine monophosphate and calcium activated Cl- transport. Inhibition of Cl- transport may contribute to common diseases of the airways, such as chronic rhinosinusitis and chronic obstructive pulmonary disease. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance in sinonasal epithelium leading to chronic rhinosinusitis. Abnormal chloride (Cl-) transport is one mechanism that contributes to this disorder, as demonstrated by the disease cystic fibrosis. Identifying safe compounds that stimulate transepithelial Cl- transport is critical to improving hydration of the ASL and promoting mucociliary transport. Sinupret (Bionorica, LLC, San Clemente, CA), a combination of naturally occurring bioflavonoids, is a widely used treatment for respiratory ailments in Europe. However, the effects of Sinupret on target respiratory epithelium have yet to be fully investigated. The present study evaluated the mechanisms underlying this bioflavonoid therapeutic on transepithelial Cl- transport in respiratory epithelium. Study Design: In vitro and in vivo investigation. Methods: Well characterized murine nasal septal epithelial (MNSE) cultures, and murine nasal potential difference (NPD) techniques were used to evaluate the effects of Sinupret on Cl- secretion. Results: The change in Sinupret-stimulated current (Δ ISC expressed as μA/cm2) in MNSE, representing Cl- secretion, was significantly increased when compared to controls (19.04 ± 1.67 μA/cm2 vs. 1.8 ± 0.35 μA/cm2, respectively; P = .00005). Transepithelial Cl- transport measured in the murine NPD in vivo assay (n = 42) was also significantly enhanced when compared to controls (-0.8 mV vs. -0.9 mV; P = .0004). Importantly, Sinupret-stimulated Cl- transport was substantially more robust in vivo than forskolin, a compound among the strongest known cystic fibrosis transmembrane conductance regulator activators (-3.8 mV vs. -1.65 mV; P = .01). Conclusions: Sinupret strongly activates transepithelial Cl- secretion through a mechanism known to hydrate the ASL of respiratory epithelium. This is one means by which the medication is likely to exert therapeutic benefit. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Although the pathophysiology leading to rhinosinusitis is complex, evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature. Normal respiratory epithelial MCC is an important host defense mechanism that is dependent on proper ciliary beating and the biological properties of the airway surface liquid (ASL). The role that tobacco smoke exposure plays as an inhibitor of MCC has yet to be elucidated. The present study investigates the consequences of cigarette smoke exposure on ciliary function and transepithelial chloride (Cl−) secretion, a major determinant of ASL. Study Design: In vitro investigation. Methods: Well-characterized primary murine nasal septal epithelial (MNSE) and human sinonasal epithelial (HSNE) cultures were exposed to cigarette smoke condensate (CSC) and compared to control cultures. Effects on ciliary beat frequency (CBF) and Cl− secretion were investigated using pharmacologic manipulation. Results: Change in forskolin-stimulated current (ΔISC), representing transepithelial Cl− secretion, was significantly decreased in CSC exposed MNSE (14.97 ± 1.2 μA/cm2 vs. control, 19.1 ± 1.56 μA/cm2 [ P = .04]) and HSNE (2.68 ± 0.79 μA/cm2 vs. control, 10.8 ± 1.73 μA/cm2) cultures ( P = .001). Forskolin-stimulated CBF was also significantly reduced when acutely exposed to CSC (5.64 ± 0.06 Hz vs. control 7.15 ± 0.18 Hz). Conclusions: The present study provides direct evidence that tobacco smoke diminishes two major components of MCC. This links tobacco smoke as a potential contributing and/or exacerbating factor in exposed individuals with chronic rhinosinusitis. Laryngoscope, 2009 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "What Is the Optimal Perioperative Management of Antiplatelet Therapy?," by R. R. Shah and A. K. Lalwani in the 2015 issue.

A response from the author of the article "Simultaneous pericranial and nasoseptal flap reconstruction of anterior skull base defects following endoscopic-assisted craniofacial resection" in a previous issue is presented.

Objectives: The management of lateral recess of the sphenoid sinus (LRS) cerebrospinal fluid (CSF) leaks presents unique challenges to the Otolaryngologist. This study highlights concepts critical to achieving successful repair and avoiding intracranial complications. Methods: Prospective evaluation of patients with LRS CSF leaks from 6/2008 to 6/2010. Results: Thirteen CSF leaks originating in the LRS were surgically repaired in 11 patients - the endoscopic transpterygoid approach was used in 12/13 repairs. Eight patients had one or multiple failed attempts at repair prior to presentation [4 endoscopic sphenoidotomies and 4 middle cranial fossa (MCF) approaches]. One patient presented with a temporal lobe abscess following hydroxyapetite "obliteration" to seal off the LRS. This required a combined MCF/transpterygoid approach to drain the abscess, remove the encephalocele and hydroxyapetite, seal the skull base defect, and establish adequate drainage for the LRS. In two cases, the LRS was left patent due to concerns of inadequate extirpation of mucosa. Median follow up was 5.8 months (0.5 to 17). One patient experienced a failure (2 months post-repair), which was successfully sealed on the second attempt. Postoperative ICP measurements were recorded on 8 patients (average 26.7 cmH20). Ten patients had postoperative intervention for intracranial hypertension (5 ventriculoperitoneal shunts, 5 maintained on acetazolamide). [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance in sinonasal epithelium leading to chronic rhinosinusitis. Abnormal chloride (Cl(-)) transport is one mechanism that contributes to this disorder, as demonstrated by the disease cystic fibrosis. Identifying safe compounds that stimulate transepithelial Cl(-) transport is critical to improving hydration of the ASL and promoting mucociliary transport. Sinupret (Bionorica, LLC, San Clemente, CA), a combination of naturally occurring bioflavonoids, is a widely used treatment for respiratory ailments in Europe. However, the effects of Sinupret on target respiratory epithelium have yet to be fully investigated. The present study evaluated the mechanisms underlying this bioflavonoid therapeutic on transepithelial Cl(-) transport in respiratory epithelium., Study Design: In vitro and in vivo investigation., Methods: Well characterized murine nasal septal epithelial (MNSE) cultures, and murine nasal potential difference (NPD) techniques were used to evaluate the effects of Sinupret on Cl(-) secretion., Results: The change in Sinupret-stimulated current (Delta I(SC) expressed as microA/cm(2)) in MNSE, representing Cl(-) secretion, was significantly increased when compared to controls (19.04 + or - 1.67 microA/cm(2) vs. 1.8 + or - 0.35 microA/cm(2), respectively; P = .00005). Transepithelial Cl(-) transport measured in the murine NPD in vivo assay (n = 42) was also significantly enhanced when compared to controls (-0.8 mV vs. -0.9 mV; P = .0004). Importantly, Sinupret-stimulated Cl(-) transport was substantially more robust in vivo than forskolin, a compound among the strongest known cystic fibrosis transmembrane conductance regulator activators (-3.8 mV vs. -1.65 mV; P = .01)., Conclusions: Sinupret strongly activates transepithelial Cl(-) secretion through a mechanism known to hydrate the ASL of respiratory epithelium. This is one means by which the medication is likely to exert therapeutic benefit.

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