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Cystic fibrosis (CF) is a multisystem disease that often requires otolaryngology care. Individuals with CF commonly have chronic rhinosinusitis but also present with hearing loss and dysphonia. Given these manifestations of CF, otolaryngologists are frequently involved in the care of patients with CF; however, there is limited consensus on optimal management of sinonasal, otologic, and laryngologic symptoms.The Cystic Fibrosis Foundation convened a multidisciplinary team of otolaryngologists, pulmonologists, audiologists, pharmacists, a social worker, a nurse coordinator, a respiratory therapist, two adults with CF, and a caregiver of a child with CF to develop consensus recommendations. Workgroups developed draft recommendation statements based on a systematic literature review, and a ≥80% consensus was required for acceptance of each recommendation statement.The committee voted on 25 statements. Eleven statements were adopted recommending a treatment or intervention, while five statements were formulated recommending against a specific treatment or intervention. The committee recommended eight statements as an option for select patients in certain circumstances, and one statement did not reach consensus.These multidisciplinary consensus recommendations will help providers navigate decisions related to otolaryngology consultation, medical and surgical management of CF-CRS, hearing, and voice in individuals with CF. A collaborative and multidisciplinary approach is advocated to best care for our patients with CF. Future clinical research is needed utilizing standardized, validated outcomes with comprehensive reporting of patient outcome, effects of modulator therapies, and genetic characteristics to help continue to advance care, decrease morbidity, and improve the quality of life for individuals with CF.

BACKGROUND: Chronic rhinosinusitis frequently occurs in people with cystic fibrosis. Several medical interventions are available for treating chronic rhinosinusitis in people with cystic fibrosis; for example, different concentrations of nasal saline irrigations, topical or oral corticosteroids, antibiotics ‐ including nebulized antibiotics ‐ dornase alfa and modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) (such as lumacaftor, ivacaftor or tezacaftor). However, the efficacy of these interventions is unclear. This is an update of a previously published review. OBJECTIVES: The objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 09 September 2021. We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 22 November 2021. SELECTION CRITERIA: Randomized and quasi‐randomized trials of different medical interventions compared to each other or to no intervention or to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines. MAIN RESULTS: We identified no trials that met the pre‐defined inclusion criteria. The most recent searches identified 44 new references, none of which were eligible for inclusion in the current version of this review; 12 studies are listed as excluded and one as ongoing. AUTHORS' CONCLUSIONS: We identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High‐quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.

Background Epithelial ion transport regulates hydration of airway mucosal surfaces, and thus promotes effective mucociliary clearance (MCC). Decreased transepithelial Cl− transport may contribute to epithelial dysfunction by abrogating MCC and increasing mucus viscosity in chronic rhinosinusitis (CRS). The objective of the current study is to evaluate Cl− channel transport properties from cultures of human sinonasal epithelia. Methods Human sinonasal epithelia (HSNE) from patients undergoing sinus surgery were cultured at an air-liquid interface to confluence and full differentiation. The epithelial monolayers were mounted in Ussing Chambers to investigate pharmacological manipulation of ion transport. Epithelial Na+ channel (via Amiloride), CFTR (via forskolin), and Ca2+-activated Cl− channel (CaCC, via UTP) transport were investigated among three different patient groups: Control, CRS and CRS with polyposis. CFTR mRNA levels were evaluated with quantitative RT-PCR. Results HSNE cultures from 18 patients (Control = 9, CRS = 6, CRS with polyposis = 3) were evaluated in 142 experiments. Summary data from the 18 patients demonstrated that stimulated CFTR-mediated anion transport (Δ ISC) was significantly lower with CRS (7.58+/−2.24 µA/cm2) compared to control (25.86+/−3.44 µA/cm2) and CRS with polyposis (20.16+/−4.0 µA/cm2) (p = 0.004). No statistically significant difference was found for CaCC anion transport between groups (p = 0.39). Significantly decreased mRNA (relative expression) was noted in CRS cultures (CRS = 40.83+/−1.76 vs. control = 116.2+/−24.27, p = 0.03). Conclusions A substantial decrease in the Cl− secretory capacity of HSNE monolayers was demonstrated in CRS subjects. Data suggest that CFTR may contribute more to abnormal ion transport in CRS than CaCC.

BACKGROUND: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. Recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, this review systematically evaluates the scientific literature and provides an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS. METHODS: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms and the overall grade of evidence. RESULTS: This review evaluated the published literature on five unique topics. Each of the following therapeutic categories was investigated explicitly with regard to treatment outcomes in patients with CF CRS: 1) nasal saline; 2) intranasal corticosteroids (INCS); 3) topical antibiotics; 4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and 5) endoscopic sinus surgery (ESS). CONCLUSION: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.

BACKGROUND: Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study is to develop and characterize an oxygen-generating biomaterial (OGB) as an innovative treatment strategy for CRS. METHODS: An OGB was fabricated by coating catalase (CA, 0.1mg/mg of beeswax (BW)) mixed with hydrophobic BW (15 or 30 mg/ml) on the surface of calcium peroxide (CPO, 30 mg/ml) and characterized using scanning electron microscopy (SEM). In-vitro releases of both oxygen and hydrogen peroxide (H(2)O(2)) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl(−) secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers. RESULTS: Three groups of OGBs [1) CPO only, 2) CPO coated with CA and BW (1:1 ratio, CPO-CA(1)-BW(1)), 3) CPO coated with and BW (1:0.5 ratio, CPO-CA(1)-BW(0.5)] were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO-CA(1)-BW(1)=0.11+/−0.003, followed by CPO-CA(1)-BW(0.5)=0.08+/−0.010 and CPO=0.05 +/−0.004 (p

BACKGROUND: The Lactococcus strain of bacteria has been introduced as a probiotic nasal rinse for alleged salubrious effects on the sinonasal bacterial microbiome. However, data regarding interactions with pathogenic bacteria within the sinuses are lacking. The purpose of this study is to assess the interaction between L. lactis and patient-derived Pseudomonas aeruginosa, an opportunistic pathogen in recalcitrant chronic rhinosinusitis (CRS). METHODS: Commercially available probiotic suspension containing L. lactis W136 was grown in an anaerobic chamber and colonies were isolated. Colonies were co-cultured with patient-derived P. aeruginosa strains in the presence of porcine gastric mucin (mimicking human mucus) for 72 hours. P. aeruginosa cultures without L. lactis served as controls. Colony forming units (CFUs) were compared. RESULTS: Six P. aeruginosa isolates collected from 5 CRS patients (3 isolates from cystic fibrosis [CF], 1 mucoid strain) and laboratory strain PAO1 were co-cultured with L. lactis. There was no statistical difference in CFUs of 5 P. aeruginosa isolates grown with L. lactis compared to CFUs without presence of L. lactis. CFU counts were much higher when the mucoid strain was co-cultured with L. lactis (CFU(+L.lactis) = 1.9 × 108 ± 1.44 × 107, CFU(−L.lactis) = 1.3 × 108 ± 8.9 × 106, p = 0.01, n = 7). L. lactis suppressed the growth of 1 P. aeruginosa strain (CFU(+L.lactis) = 2.15 × 108 ± 2.9 × 107, CFU(−L.lactis) = 3.95 × 108 ± 4.8 × 106, p = 0.03, n = 7). CONCLUSION: L. lactis suppressed the growth of 1 patient P. aeruginosa isolate and induced growth of another (a mucoid strain) in in vitro co-culture setting in the presence of mucin. Further experiments are required to assess the underlying interactions between L. lactis and P. aeruginosa.

Objectives Children with cystic fibrosis (CF) have a high incidence of chronic rhinosinusitis (CRS); however, no clinical care guidelines currently exist for the management of CRS in these patients. As a result, there is variation in the treatment of CRS in children, especially when it comes to the frequency of surgery for nasal polyposis. Methods A 28-question survey was sent to pediatric otolaryngologists (POs) and pulmonologists (PPs) who care for pediatric CF patients. Questions assessed the level of agreement that practitioners had with various approaches to CRS care in pediatric CF patients. Results Responses from 114 POs and 50 PPs were included in our final analysis. Each group demonstrated significantly different approaches to the medical and surgical management of CRS in pediatric CF patients. POs prefer multi-modal approach while PPs prefer single-modal approaches. With respect to medical management, PPs incline towards IV antibiotics while POs tend toward oral steroids. Conclusion POs and PPs strongly agree that CRS has an impact on overall disease state and quality of life of pediatric CF patients. However, POs and PPs significantly differ in their approach to treating CRS, demonstrating a potential need for clinical care guidelines for the management these common sequelae of CF.

BACKGROUND Spontaneous skull base defects can result in life-threatening intracranial complications (ICCs), including meningitis and pneumocephalus. Endoscopic skull base reconstruction (ESBR) has traditionally been the treatment of choice, but its impact upon ICCs is not known. In this study, we aimed to describe the incidence rate of preoperative ICCs in patients with spontaneous skull base defects, risk factors associated with ICC development, and the impact of surgical repair on the incidence rate of ICCs. METHODS A retrospective review was performed of all spontaneous skull base defects undergoing ESBR from 2005 to 2019 at 2 academic tertiary care medical centers. The incidence rate of ICCs and the demographics information and risk factors were collected. RESULTS In 222 spontaneous skull base defects, preoperative ICCs occurred in 46 subjects (20.7%) with an incidence rate of 22.7 per 100 person-years. Factors significantly associated with preoperative ICCs included symptom duration, reduced body mass index (BMI), resolved cerebrospinal fluid rhinorrhea, and location in the frontal or lateral sphenoid sinuses. Endoscopic repair was successful in 97.2% of subjects and the postoperative ICC incidence rate was significantly reduced at 0.8 per 100 person-years (p < 0.001). CONCLUSION Spontaneous skull base defects pose significant risk for life-threatening ICCs. Our findings reveal significantly elevated odds of ICC development associated with resolved CSF rhinorrhea, lower BMI, longer duration of symptoms, and defect location. Endoscopic repair is highly successful with low morbidity and significantly reduces the incidence rate of intracranial complications.

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, 2021.

Lipopolysaccharide (LPS) serves as the interface between gram-negative bacteria (GNB) and the innate immune response in respiratory epithelial cells (REC). Herein, we describe a novel biological role of LPS that permits GNB to persist in the respiratory tract through inducing CFTR and mucociliary dysfunction. LPS reduced cystic fibrosis transmembrane conductance regulater (CFTR)-mediated short-circuit current in mammalian REC in Ussing chambers and nearly abrogated CFTR single channel activity (defined as forskolin-activated Cl- currents) in patch clamp studies, effects of which were blocked with toll-like receptor (TLR)-4 inhibitor. Unitary conductance and single-channel amplitude of CFTR were unaffected, but open probability and number of active channels were markedly decreased. LPS increased cytoplasmic and mitochondrial reactive oxygen species resulting in CFTR carbonylation. All effects of exposure were eliminated when reduced glutathione was added in the medium along with LPS. Functional microanatomy parameters, including mucociliary transport, in human sinonasal epithelial cells in vitro were also decreased, but restored with co-incubation with glutathione or TLR-4 inhibitor. In vivo measurements, following application of LPS in the nasal cavities showed significant decreases in transepithelial Cl- secretion as measured by nasal potential difference (NPD) – an effect that was nullified with glutathione and TLR-4 inhibitor. These data provide definitive evidence that LPS-generated reactive intermediates downregulate CFTR function in vitro and in vivo which results in cystic fibrosis-type disease. Findings have implications for therapeutic approaches intent on stimulating Cl- secretion and/or reducing oxidative stress to decrease the sequelae of GNB airway colonization and infection., Graphical abstract Image 1

Background The association between spontaneous cerebrospinal fluid (CSF) leak/rhinorrhea and idiopathic intracranial hypertension (IIH) has been increasingly recognized over the last years. However, considerable variability of opinion regarding the assessment, investigations, and management of patients with spontaneous CSF rhinorrhea remains. Methods A consensus group was formed from experts from Europe, Asia, Australia, South and North America. Following literature review and open discussions with members of the panel, a set of 61 statements was produced. A modified Delphi method was used to refine expert opinion with 3 rounds of questionnaires and a consensus group meeting in Santo-Rhino meeting in September 2019. Results Fifty statements (82% of total) on spontaneous CSF leak and IIH reached consensus. In 38 of 50 statements, the median response was 7 (strongly agree) and in the 12 remaining statements the median response was 6 (agree). Eleven statements were excluded because they did not reach consensus and one new statement was added during SantoRhino meeting. The final statements refer to patient history and clinical examination ("History taking should include presence of headache, tinnitus and visual defects"), investigations (role of Thin Slice Computed Tomography and CISS/FLAIR sequences in Magnetic Resonance Imaging), principles of management (watchful waiting or measures to reduce ICP are supplementary but cannot subsitute surgical closure), surgical technique, intraoperative, early postoperative and long term management. Conclusion We present fifty consensus statements on the diagnosis, investigation, and management of spontaneous CSF rhinorrhea based on the currently available evidence and expert opinion. Although by no means comprehensive and final, we believe they can contribute to the standardization of clinical practice. Early diagnosis, prompt surgical closure of the defect, assesment for and treatment of potentially co-existing idiopathic intracranial hypertension in a comprehensive multidisciplinary approach are essential in order to successfully manage spontaneous CSF rhinorrhea, reduce associated morbidity and prevent recurrence.

ObjectiveFrontal sinus osteomyelitis is a severe complication which can result from chronic rhinosinusitis, trauma, or as a complication of reconstruction or obliteration of the frontal sinus. The objective of the current study is to evaluate the contemporary management of frontal sinus osteomyelitis in light of recent advancements in endoscopic surgical techniques.MethodsReview of a prospectively collected database of patients with frontal sinus pathology was performed from 2008–2020. Data from individuals with frontal sinus osteomyelitis was collected including demographics, etiology, surgical technique, adjunctive medical treatments, complications, and clinical follow up.ResultsSixteen patients (average age 48.3, range 8–84) were included in the study. An open approach was utilized in 6 patients (2 osteoplastic flaps, 3 Reidel procedures, 1 cranialization). Seven patients underwent completely endoscopic approaches (3 Draf IIB, 4 Draf III), while 3 individuals had combined procedures (Lynch with Draf III, osteoplastic flap + Draf III, fistula excision + Draf IIb). All patients received 6 weeks of antibiotics. Average clinical follow up was 24.4 months with no patients requiring revision procedures.ConclusionEndoscopic, endoscopic-assisted, and open approaches were utilized successfully in the current series of patients with osteomyelitis of the anterior table of the frontal sinus. While the progression of endoscopic techniques allows an additional surgical treatment option, it is important to select patients appropriately as open procedures continue to have an important role in the treatment algorithm.

Endoscopic surgery on the maxillary sinus has experienced significant advances in technique and approaches since the maxillary antrostomy was introduced in the 1980s. Disease processes that previously required open surgical approaches to the maxillary sinus can now be treated endoscopically while preserving form and function of the sinus and without injuring the maxillary sinus mucosa or disrupting normal mucociliary clearance. Understanding the techniques described in this article will allow surgeons to appropriately plan treatment strategies for patients with a variety of maxillary sinus diseases from dentoalveolar origin.

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

BACKGROUND Anterior cephaloceles are rare congenital malformations that have historically been corrected via open approaches. Although the advent of endoscopic endonasal surgery has provided a minimally invasive and theoretically less morbid approach to the anterior skull base, whether endoscopic approaches provide superior treatment outcomes to open techniques has yet to be elucidated. The objective of this study was to systematically review the available literature regarding presentation and outcomes of open vs endoscopic repair of congenital anterior cephaloceles. METHODS A systematic review of the PubMed, Embase, CINAHL, and Cochrane databases was performed on January 15, 2020, to identify studies from the past 50 years reporting cases of congenital anterior cephaloceles. Data on gender, age at operation, imaging modality, cephalocele location, operative approach, and intra- and postoperative complications were collected. RESULTS Nonduplicated data (153 articles) consisted of 781 patients with congenital anterior encephaloceles. Surgical outcomes were reported in 349 patients (222 open approaches, 127 endoscopic approaches), with an average age of 4.6 years. There was a 1.3:1 male-to-female ratio. Clinical presentation included nasal obstruction (n = 154), hypertelorism (n = 106), and cleft lip/palate (n = 100). Defects were classified as sincipital (n = 479) or basal (n = 257), with 45 patients broadly classified as anterior. The number of complications experienced per operation was 0.13 for endoscopic and 0.44 for open approaches (p < 0.0001). Mortality was significantly lower for the endoscopic group compared with patients treated with open surgery (0.008 vs 0.05, p < 0.05). CONCLUSION Endoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.

BACKGROUND We recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti-inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs). METHODS Pseudomonas aeruginosa lipopolysaccharide (LPS)-stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin-8 (IL-8) secretion was quantified by enzyme-linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance [TEER], paracellular permeability [fluorescein isothiocyanate-labeled dextran], lactate dehydrogenase [LDH] assays) and function (ciliary beat frequency [CBF]) were also evaluated. RESULTS Azithromycin significantly reduced secreted IL-8 from P. aeruginosa LPS-stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin [6 μg/mL] = 4.58 ± 0.40 ng/mL, azithromycin [60 µg/mL] = 4.31 ± 0.06, azithromycin [180 µg/mL] = 4.27 ± 0.26 ng/mL, p < 0.05). Co-incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS-stimulated HSNECs also displayed a significant reduction in secreted IL-8 when compared to P. aeruginosa LPS alone (co-treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function. CONCLUSION Azithromycin decreased P. aeruginosa LPS IL-8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti-inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS.

Chronic rhinosinusitis (CRS) is a heterogenous disease process affecting a significant proportion of the population and impacting quality of life and productivity. Historically, CRS has been classified broadly into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Increased understanding regarding unique presentations of CRS subsets and their underlying inflammatory profiles has led to a new system for classifying CRS phenotypes. Consideration of CRS phenotypes has traditionally been a key factor in determining treatment paradigms. Under a new phenotype classification system, physical findings will continue to drive treatment decisions, but with more precision. Recent rapidly accumulated knowledge indicates that the broad categorization of CRSwNP or CRSsNP is no longer clinically useful. Reorganization of CRS phenotypes and their underlying endotypes will lead to more targeted and efficacious therapy.

Background Advanced-stage olfactory neuroblastoma requires multimodal therapy for optimal outcomes. Debate exists over endoscopic endonasal surgery in this situation. Stage-matched open and endoscopic surgical therapy were compared. Methods Patients from 6 cancer institutions were assessed. Stratification included dural involvement, Kadish stage, nodal disease, Hyams' grade, approach, and margin status. At follow-up, local control, nodal status, and evidence of distant metastases were recorded with any subsequent therapy. Statistical analyses to identify risk factors for developing recurrence and survival differences were performed. Results One hundred nine patients were assessed (age 49.2 ± 13.0 years; 46% women) representing Kadish A stage (10%), Kadish B stage (25%), and Kadish C stage (65%). The majority of the patients (61.5%) underwent endoscopic resection, 53.5% within Kadish C stage. Within-stage survival analysis favored endoscopic subgroup for Kadish C stage (log-rank P = .017) nonsignificant for Kadish B stage (log-rank P = .39). Conclusion Stage-matched survival was better for the endoscopically treated group compared to the open surgery group, with high negative margin resections obtained.

Traditionally, frontal sinus trauma has been treated using open incisions to access the anterior and/or posterior table. Mounting evidence indicates frontal sinus trauma can be managed using an endoscopic endonasal approach (EEA) with less morbidity. Such an approach permits preservation of a functional sinus and less reliance on computed tomography for postoperative follow up. The goal of this article is to highlight a shift in paradigm away from open approaches using external incisions towards an EEA to repair cerebrospinal fluid (CSF) leaks and fractures of the frontal sinus.In a prospective case series of 46 patients undergoing EEA to frontal sinus fractures, 41 patients had active CSF leaks arising from the posterior table of the frontal sinus. A successful endoscopic repair was achieved in 97.6% with only one patient requiring revision Draf IIB surgery. Anterior table fractures were also successfully reduced with excellent cosmesis.Endoscopic repair of frontal sinus fractures and CSF leaks is effective and well tolerated. In select patients, it is the preferred treatment as it maintains normal sinus structure and function, minimizing both early and late complications.

BACKGROUND Mucociliary clearance is a main defense mechanism of the airway and is impaired in ciliary dyskinesia. The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia. METHODS Bronchiectasis patients referred to a rhinology clinic for nasal brush biopsy (NBB) were included in this study. NBB was performed using a curettage technique whereby ciliated epithelial cells were obtained from the surface of the inferior nasal turbinate. Results of transmission electron microscopy findings, primary ciliary dyskinesia (PCD) gene (35 genes) analyses (Invitae), and sinus computed tomography (CT) scans were reviewed. RESULTS Twenty-three patients (age, 54 ± 2.9 years) were referred for NBB between 2015 and 2018. Thirteen patients (56.5%) met the criteria for diagnosis of CRS. Nineteen patients had ciliary ultrastructural defects. The most common finding was compound cilia (n = 11, 47.8%). Five patients (21.7%) had central microtubule defects (CMD) with higher forced expiratory volume in 1 second (FEV1 ) at the time of referral than those without CMD (CMD+ , 91 ± 3.7%; CMD- , 73.5 ± 5.7%; p = 0.023). Of 15 subjects with a PCD gene panel, 67% (9 of 15) carried at least 1 gene associated with PCD. Only 1 patient reached diagnosis of PCD. Approximately 50% of non-PCD carriers had a smoking history (p < 0.05). Lund-Mackay scores did not significantly differ between PCD and non-PCD carriers (p = 0.72). CONCLUSION Nearly half of bronchiectasis patients referred for NBB had concurrent CRS. The presence of ciliary abnormalities was not amplified in bronchiectasis patients with CRS compared to those without CRS. Extrinsic factors may be related to ciliary structural abnormalities in non-PCD gene carriers.

Objective: To define a new anatomic relationship in pediatric sinus surgery, assessing the maxillary roof as a constant safe landmark to avoid skull base injury in the pediatric population. Study Design: Retrospective analysis. Setting: Tertiary care children hospital. Subjects and Methods: A retrospective analysis was performed of all computed tomography scans of the sinuses and facial bones at the emergency department of a tertiary children’s hospital over the course of a year. Radiographic measurements included the lowest cribriform plate and planum sphenoidale (PS) heights, or posterior skull base when not yet pneumatized, as well as the highest maxillary roof height. The nasal floor was used for reference. Statistics were performed via Shapiro-Wilks test with a P-value of .05 indicating statistical significance. Results: Three hundred and seven unique scans were reviewed (38.9% female; n = 122; P = .58). Age stratification was based on previously described sinus growth patterns. In all patients, the maximum maxillary height was inferior to the lowest measured cribriform lamella and PS ( P Conclusion: Despite variation in sinus growth and development in children, the current study demonstrated the validity of the maxillary sinus roof as a constant safe landmark in the pediatric population, offering a novel anatomic relationship for teaching safety in performing pediatric sinus surgery. Level of Evidence: 4

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although impairment of mucociliary clearance contributes to severe morbidity and mortality in people with CF, a clear understanding of the pathophysiology is lacking. This is in part due to the absence of clinical imaging techniques capable of capturing CFTR-dependent functional metrics at the cellular level. Here, we report the clinical translation of a 1-μm resolution micro-optical coherence tomography (μOCT) technology to quantitatively characterize the functional microanatomy of human upper airways. Using a minimally-invasive intranasal imaging approach, we performed a clinical study on age- and sex-matched CF and control groups. We observed delayed mucociliary transport rate at the cellular level, depletion of periciliary liquid layer, and prevalent loss of ciliation in subjects with CF. Distinctive morphological differences in mucus and various forms of epithelial injury were also revealed by μOCT imaging and had prominent effects on the mucociliary transport apparatus. Elevated mucus reflectance intensity in CF, a proxy for viscosity in situ, had a dominant effect. These results demonstrate the utility of μOCT to determine epithelial function and monitor disease status of CF airways on a per-patient basis, with applicability for other diseases of mucus clearance.

Primary spontaneous cerebrospinal fluid (CSF) rhinorrhea is an unusual phenomenon that may occur anywhere along the skull base. However, CSF leaks originating from clival defects are rarely reported in the literature. The majority of reported cases were managed with microscopic techniques, using free grafts. The present study discusses a case of spontaneous CSF rhinorrhea from a clival defect closed with our transnasal operative approach using endoscopic techniques. The skull base defect was successfully managed with an endoscopic binostril approach to create a nasal septal flap pedicled at the sphenopalatine artery, while also preserving the integrity of the nasal septum.

Encephaloceles and cerebrospinal fluid (CSF) leaks of the frontal sinus may result from congenital, traumatic, spontaneous, or neoplastic causes. Paramount to success is adequate preoperative planning with accurate history, physical exam, endoscopy, imaging, and testing to confirm location of the leak and origin of the disease. Generally, frontal sinus CSF leaks may be addressed endoscopically with favorable anatomy, proper surgical technique, and appropriate equipment. Open surgical approaches (eg, osteoplastic flap) are often required for superior/lateral defects or if the surgeon is not experienced with endoscopic frontal sinus techniques.

Background The COVID-19 pandemic has radically shifted healthcare operations within hospitals and universities across the globe. However, the effect of the COVID-19 pandemic on research endeavors and clinical trials is unclear. Objective This study investigates the impact of the COVID-19 pandemic on basic science and clinical research within the rhinology community. Methods A cross-sectional study was designed utilizing an 8-question survey to identify changes to rhinology research. Questions evaluated the impact of the COVID-19 pandemic on administrative research support and staffing, basic science research, clinical trials and resident research involvement. Results Seventy-one participants responded to the survey (8.5% response rate). Most respondents noted changes in IACUC/IRB approval (faster, 33%; slower, 31%). Of those who employed laboratory personnel, 64% were able to continue staff employment with full salary. The majority of animal research and in vitro studies were halted (64% and 56%, respectively), but animal care and cell line maintenance were allowed to continue. Clinical trial enrollment was most commonly limited to COVID derived studies (51%). Forty-seven percent of respondents noted increased resident research participation. Conclusion The rapid spread of the SARS-CoV-2 virus has markedly impacted rhinology-related research. Maintaining safe workplace practices as restrictions are lifted will hopefully mitigate the spread of the virus and allow research productivity to resume.

BACKGROUND Sinonasal and skull-base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull-base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull-base and medial orbital wall defects. METHODS An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull-base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale. RESULTS Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks). CONCLUSION The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull-base defects and simultaneous medial orbital wall defects.

Objectives Congenital encephaloceles provide unique diagnostic and reconstructive challenges for the pediatric rhinologist. The objectives of the current study were to evaluate contemporary treatment strategies for congenital encephaloceles focusing on presentation, surgical technique, and outcomes. Methods Multi-institutional retrospective chart review of congenital encephaloceles (2003–2019). Data regarding demographics, presenting symptoms, associated abnormalities, surgical technique, size, location, and complications were collected. Results Fourteen patients with 15 congenital encephaloceles were treated using endoscopic techniques (avg 6.0 years, range 2 months–22 years) with mean follow up of 23 months. The majority presented with nasal obstruction (n = 13); only one child had cerebrospinal fluid (CSF) rhinorrhea. Associated anomalies included nasal deformities, congenital hypopituitarism, and Morning Glory syndrome. Average encephalocele size was 2.44 cm (range 0.5–3.6 cm) with mean skull base defect size of 8.6 x 7.7 mm. Locations included the foramen cecum (n = 9), central sphenoid (n = 3), midline anterior cranial fossa (n = 1), orbital plate of frontal bone (n = 1), and ethmoid roof (n = 1). Because of favorable expansion from encephaloceles, it was unnecessary to postpone surgeries to allow nasal cavity growth. Three individuals had prior operations, including surgeries for “nasal polyp” or “adenoid cyst”. Two patients had post-operative complications (meningitis and CSF leak) effectively treated with no further sequelae. Conclusions In the current study, congenital encephaloceles in children as young as 2 months were successfully repaired using endoscopic techniques. Endoscopic approaches remain a safe and effective intervention for management of these lesions.

Background Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull-base surgery have produced the International Consensus Statement on Endoscopic Skull-Base Surgery (ICAR:ESBS). Methods Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence-based review or evidence-based review with recommendations format. Subsequently, each topic was written and then reviewed by skull-base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. Results The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull-base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. Conclusion A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence-based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull-base community to embrace these opportunities and collaboratively address these shortcomings.

Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that improves pulmonary function in cystic fibrosis (CF) patients with at least 1 copy of the G551D CFTR mutation. The purpose of this study is to evaluate the impact of ivacaftor on chronic rhinosinusitis (CRS) symptoms in this population.The G551D Observational (GOAL) study was a multicenter prospective cohort study enrolling CF patients ≥6 years with at least 1 G551D mutation. Subjects were provided 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaires prior to ivacaftor therapy and at 1, 3, and 6 months afterward. The impact on rhinologic (R), psychological (P), sleep (S), and ear/facial (E) quality of life (QOL) domains was evaluated separately.Of 153 subjects, 129 (84%) completed all questionnaires. Typical baseline symptom burden was low (75% with scores1) and degree of improvement (ie, reduced scores) was greater with higher baseline scores. SNOT-20 decreased, reflecting improvement, at all follow-up intervals (1 month: [mean change ± standard deviation] -0.25 ± 0.53, p0.01; 3 months; -0.29 ± 0.58, p0.01; 6 months: -0.21 ± 0.58, p = 0.02), but less than the prespecified minimal clinically important difference (0.8). Significant improvement was observed at 1, 3, and 6 months in the R domain (1 month: -0.24, p0.01; 3 months: -0.34, p0.01; 6 months: -0.25, p0.01) and P domain (1 month: -0.25, p0.01; 3 months: -0.32, p0.01; 6 months: -0.26, p0.01), and 1 and 3 months in the S domain (1 months: -0.35, p0.01; 3 months: -0.32, p0.01; 6 months: -0.18, p = 0.07). There was no improvement in the E domain at any time point.Ivacaftor improves QOL in the R, P, and S domains in G551D CF patients, although QOL instruments validated for CRS may not translate well to CF CRS patients because symptom burden was surprisingly low.

Background The osteoplastic flap provides access to pathology of the frontal sinus and is often performed with obliteration, which can result in significant long-term complications. Objective To describe the authors’ approach to osteoplastic flap without obliteration. Methods Descriptive analysis. Results Osteoplastic flap without obliteration preserves frontal sinus function while permitting direct access to the frontal sinus. In this study, we demonstrate a combined nonobliterated approach, accessing the frontal sinus with a Draf III approach to remove a large frontal sinus osteoma. Conclusion The approach provides excellent exposure for large tumors not otherwise accessible via purely endoscopic procedures, permits improved surveillance, and minimizes long-term complications of obliterated sinuses.

Olfactory neuroblastoma and the management of neck disease has posed considerable challenges to the treating physician. The aims of the study were to determine the incidence and factors influencing neck disease and to identify at-risk patients with cervical node-negative disease at presentation.Multicenter case series with retrospective chart review.In sum, 113 patients with a histopathologic diagnosis of olfactory neuroblastoma across 6 tertiary hospitals in Australia and the United States.Treatment modalities for the primary site and neck included surgery, radiotherapy, and combined therapy. Treatment outcomes were measured in relation to date of primary treatment, and long-term follow-up was recorded. Disease-free survival was calculated as time for patients to develop delayed neck disease following primary treatment.A total of 113 patients (46 females, 49.7 ± 13.2 years) were identified with a median follow-up of 41.5 months (interquartile range, 58.2); 7.1% of patients presented with primary neck disease, while 8.8% of patients presented with delayed neck disease. Neck disease was present in patients with Hyams grade II (22.2%), III (55.6%), and IV (22.2%) lesions (χ(2) = 5.66, P = .13). Histologic grade was higher in patients with primary neck disease (χ(2) = 16.22, P = .001). Positive surgical margins were associated with a higher risk of delayed neck disease as compared with clear surgical margin (17.9% vs 5%, P = .034).Neck metastasis is an important clinical consideration for olfactory neuroblastoma at presentation and in surveillance. Primary treatment of the neck could be considered in select patients. Long-term surveillance of the neck and primary site is essential.

Background Transnasal endoscopic pituitary surgery has proven to be a safe and effective method for removing pituitary tumors. Direct and angled endoscopy at the site of dissection provides excellent visualization without external incisions. However, olfactory loss has been documented after surgical approaches to the pituitary and is accompanied by a significant detriment to quality of life. Study Design A prospective cohort study. Methods Subjects 19 years and older who were undergoing transnasal endoscopic pituitary surgery were recruited for this study. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and then at 3–4 months. Data regarding demographics, reconstructive technique, and complications were recorded. The patients had skull-base reconstruction with a Medpore implant or a vascularized nasoseptal flap. Results and Discussion A total of 33 subjects were recruited, with 18 completing the study. The mean (SEM) age was 58.2 ± 2.4 years, with 12 females and 6 males. The majority of patients (89%) had nonfunctioning macroadenomas, and six individuals had reconstruction by using a vascularized nasoseptal flap. Matched mean (SEM) preoperative and postoperative UPSIT scores for this cohort were not significantly different (31.3 ± 0.4 versus 30.5 ± 0.5, respectively; p = 0.54). In addition, there was no significant difference between the mean preoperative and postoperative UPSIT scores of the patients who had nasoseptal flaps (29.4 ± 1.1 vs. 28.6 ± 1.3 respectively; p = 0.87). Conclusions In the current study, pre- and postoperative UPSIT scores were not significantly different in patients who underwent endoscopic transnasal pituitary surgery. The use of a nasoseptal flap also did not adversely affect postoperative UPSIT scores.

Background Intraoperative image guidance is a useful modality for transsphenoidal pituitary surgery. However, the outcomes associated with this technology have not been systematically evaluated. Objective The purpose of the study was to quantify complication rates with and without the use of image guidance during transsphenoidal pituitary surgery using a nationwide database with broadly applicable results. Methods A retrospective analysis of the Nationwide Inpatient Sample was performed from 2007 to 2011. Transsphenoidal pituitary resections for adenomas were identified by International Classification of Diseases-9th Revision, Clinical Modification code. The effect of image guidance on cerebrospinal fluid (CSF) leak complications and cost-benefit was analyzed. Results A total of 48,848 transsphenoidal pituitary resections were identified, of which 77.5% were partial resections and 22.5% were complete. Pathologic indications included benign (89.3%), malignant primary (0.6%), and malignant secondary (0.4%). Complications included same-stay death (0.4%), CSF leak (8.8%), postoperative CSF rhinorrhea (1.9%), diabetes insipidus (12.4%), and meningitis (0.4%). Image guidance was employed in 7% (n = 3401) of all cases. When analyzed by modality, computed tomography (CT)-assisted procedures had lower CSF rhinorrhea rates (1.1%) compared with cases with no image guidance (1.9%), whereas magnetic resonance (MR)-assisted procedures had the highest rates (2.7%, χ2 p < 0.001). Rates of CSF leak demonstrated a similar pattern (CT 6.4%, no image guidance 8.9%, MR 9.2%, χ2 p < 0.001). CT-assisted surgery had significantly shorter length of stay (2.9 days) versus no image guidance (3.7 days, p < 0.001), lower total charges ($47,589 versus $62,629, p < 0.001), and lower total cost ($16,748 versus $20,530, p < 0.001). Conclusions CT-assisted surgery is associated with a lower rate of CSF leak, shorter length of stay, and lower cost compared with patients without image guidance. Further studies that control for severity and extent of disease are warranted to confirm this finding.

To better understand upper airway tissue regeneration, the exposed cartilage and bone at donor sites of tissue flaps may serve as in vivo "Petri dishes" for active wound healing. The pedicled nasoseptal flap (NSF) for skull-base reconstruction creates an exposed donor site within the nasal airway. The objective of this study is to evaluate whether grafting the donor site with a sinonasal repair cover graft is effective in promoting wound healing.In this multicenter, prospective trial, subjects were randomized to intervention (graft) or control (no graft) intraoperatively after NSF elevation. Individuals were evaluated at 2, 6, and 12 weeks postintervention with endoscopic recordings. Videos were graded (Likert scale) by 3 otolaryngologists blinded to intervention on remucosalization, crusting, and edema. Scores were analyzed for interrater reliability and cohorts compared. Biopsy and immunohistochemistry at the leading edge of wound healing was performed in select cases.Twenty-one patients were randomized to intervention and 26 to control. Subjects receiving the graft had significantly greater overall remucosalization (p = 0.01) than controls over 12 weeks. Although crusting was less in the small intestine submucosa (SIS) group, this was not statistically significant (p = 0.08). There was no overall effect on nasal edema (p = 0.2). Immunohistochemistry demonstrated abundant upper airway basal cell progenitors in 2 intervention samples, suggesting that covering grafts may facilitate tissue proliferation via progenitor cell expansion.This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards.

Background: Rabbits are useful for preclinical studies of sinusitis because of similar physiologic features to humans. The objective of this study is to develop a rabbit model of sinusitis that permits assessment of microanatomy and sampling for evaluating shifts in the sinus microbiota during the development of sinusitis and to test how the mucociliary clearance (MCC) defect might lead to dysbiosis and chronic rhinosinusitis (CRS).Methods: Generation of CRS was accomplished with an insertion of a sterile sponge into the left middle meatus of New Zealand white rabbits (n = 9) for 2 weeks. After sponge removal, 4 rabbits were observed for another 10 weeks and evaluated for CRS using endoscopy, microCT, visualization of the functional micro-anatomy by micro-optical coherence tomography (μOCT), and histopathological analysis of the sinus mucosa. Samples were taken from the left middle meatus and submitted for microbiome analysis.Results: CT demonstrated opacification of all left sinuses at 2 weeks in all rabbits (n = 9), which persisted in animals followed for another 12 weeks (n = 4). Histology at week 2 showed mostly neutrophils. On week 14, significant infiltration of plasma cells and lymphocytes was noted with increased submucosal glands compared to controls (p = 0.02). Functional microanatomy at 2 weeks showed diminished periciliary layer (PCL) depth (p < 0.0001) and mucus transport (p = 0.0044) compared to controls despite a thick mucus layer. By 12 weeks, the thickened mucus layer was resolved but PCL depletion persisted in addition to decreased ciliary beat frequency (CBF; p < 0.0001). The mucin fermenting microbes (Lactobacillales, Bacteroidales) dominated on week 2 and there was a significant shift to potential pathogens (e.g., Pseudomonas, Burkholderia) by week 14 compared to both controls and the acute phase (p < 0.05).Conclusion: We anticipate this reproducible model will provide a means for identifying underlying mechanisms of airway-surface liquid (ASL) depletion and fundamental changes in sinus microbial communities that contribute to the development of CRS. The rabbit model of sinusitis exhibited diminished PCL depth with delayed mucus transport and significant alterations and shift in the sinus microbiome during the development of chronic inflammation.

Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms.P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs.l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 μg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 μg/mL), a synergistic anti-biofilm effect was noted at 0.05 μM and 0.5 μM of l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone.Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned.

BACKGROUND: Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within CF airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS. METHODS: Mucosal explants from patients with and without CRS were submerged in Ringer’s solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plugin of ImageJ. RESULTS: Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs. Controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53+/-0.67 vs controls, 4.86+/-1.68; p

Introduction: Pseudomonas aeruginosa infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many P. aeruginosa strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. Aim: To assess the activity of a phage cocktail in eradicating biofilms of ex vivo P.aeruginosa isolates from CRS patients. Methods: P. aeruginosa isolates from CRS patients with and without cystic fibrosis (CF) across three continents were multi-locus sequence typed and tested for antibiotic resistance. Biofilms grown in vitro were treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured after 24 and 48 h, using a crystal violet assay. Phage titrations were performed to confirm replication of the phages. A linear mixed effects model was applied to assess the effects of treatment, time, CF status, and multidrug resistance on the biomass of the biofilm. Results: The isolates included 44 strain types. CT-PA treatment significantly reduced biofilm biomass at both 24 and 48 h post-treatment (p < 0.0001), regardless of CF status or antibiotic resistance. Biomass was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by a rise in phage titres for all except one strain. Conclusion: A single dose of phages is able to significantly reduce biofilms formed in vitro by a range of P.aeruginosa isolates from CRS patients. This represents an exciting potential and novel targeted treatment for P. aeruginosa biofilm infections and multidrug resistant bacteria.

Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (ClPrimary HSNE cell cultures were subjected to a 1% oxygen environment for 12 hours to induce acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Ion transport characteristics were assessed with pharmacologic manipulation in Ussing chambers. ASL, periciliary fluid (PCL), and ciliary beat frequency (CBF) were evaluated using μOCT.Amiloride-sensitive transport (ΔIHypoxia-induced defects in epithelial anion transport in HSNE led to predictable effects on markers of MCC measured with novel μOCT imaging. This imaging method represents a technological leap forward and is feasible for assessing acquired defects impacting the airway surface.

PURPOSE OF REVIEW Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. RECENT FINDINGS The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. SUMMARY Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention.

Background Chronic rhinosinusitis with nasal polyposis (CRS/NP) is a medical disease that is managed more effectively after endoscopic sinus surgery (ESS). Despite topical treatment with intranasal steroids, acute inflammatory exacerbations (AEs) are common and are typically treated with oral prednisone, which has significant and well-documented side effects. The objective of the current study was to critically evaluate the topical application of triamcinolone acetonide (80) in carboxymethylcellulose (TA/CMC) foam for AEs in CRS/NP patients after ESS. Methods CRS/NP patients managed with ESS by a single rhinologist over a 5-year period were included in the study. Data were reviewed regarding demographics, number of AEs, revision surgery, 22-item Sino-Nasal Outcomes Test (SNOT-22) scores, frequency of oral prednisone and/or TA/CMC, and notable side effects. Results A total of 371 CRS/NP patients were treated with ESS over a 5-year period. Mean follow-up was 49.3 weeks (range, 2–249 weeks). During this time period, 130 patients (46 years; range, 28–48 years) developed a cumulative 267 AEs. Before initiating use of TA/CMC in 2010, 66 AEs were treated with prednisone. Subsequently, 116 of 201 AEs were managed with TA/CMC with a sequential decrease in prednisone use over the last 3 years (77, 39, and 32%). SNOT-22 scores (n = 33) decreased significantly after TA/CMC instillation (preinstillation, 1.69 ± 0.86, versus postinstillation, 1.23 ± 0.8; p < 0.01). Conclusion Management of AEs with TA/CMC decreased overall prednisone use in a large population of CRS/NP patients in this retrospective evaluation. TA/CMC appears well tolerated and is a useful treatment option for AEs in postoperative CRS/NP patients.

BACKGROUND AND IMPORTANCE Olfactory tract dysfunction due to an unruptured intracranial aneurysm is rare. We present a case in which a patient with impaired olfaction related to bilateral internal carotid artery aneurysms experienced subjective and quantitative objective improvement of olfactory sensation after treatment of ophthalmic segment aneurysms with flow diversion. CLINICAL PRESENTATION A 44-year-old woman presented with hyposmia and bilateral ophthalmic segment internal carotid artery aneurysms. The symptom of hyposmia, worsening over a period of several months, was suspected to be due to mass effect from bilateral unruptured ophthalmic segment aneurysms pressing on the olfactory tracts. Each aneurysm was treated with a Pipeline embolization device (PED). Follow-up angiography at 5 months showed occlusion of both aneurysms. The patient experienced subjective improvement in olfaction and complete objective resolution of her hyposmia as measured by the validated University of Pennsylvania Smell Identification Test (UPSIT). CONCLUSION Intracranial aneurysms causing dysfunction of olfactory sensation due to mass effect upon the olfactory tract can be successfully treated with flow diversion. Flow diversion should be considered as one of the treatment options for patients with cranial nerve dysfunction due to unruptured intracranial aneurysms.

Background Advances in the care of patients with cystic fibrosis (CF) have improved pulmonary outcomes and survival. In addition, rapid developments regarding the underlying genetic and molecular basis of the disease have led to numerous novel targets for treatment. However, clinical and basic scientific research focusing on therapeutic strategies for CF-associated chronic rhinosinusitis (CRS) lags behind the evidence-based approaches currently used for pulmonary disease. Methods This review evaluates the available literature and provides an update concerning the pathophysiology, current treatment approaches, and future pharmaceutical tactics in the management of CRS in patients with CF. Results Optimal medical and surgical strategies for CF CRS are lacking because of a dearth of well-performed clinical trials. Medical and surgical interventions are supported primarily by level 2 or 3 evidence and are aimed at improving clearance of mucus, infection, and inflammation. A number of novel therapeutics that target the basic defect in the cystic fibrosis transmembrane conductance regulator channel are currently under investigation. Ivacaftor, a corrector of the G551D mutation, was recently approved by the Food and Drug Administration. However, sinonasal outcomes using this and other novel drugs are pending. Conclusion CRS is a lifelong disease in CF patients that can lead to substantial morbidity and decreased quality of life. A multidisciplinary approach will be necessary to develop consistent and evidence-based treatment paradigms.

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

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.Prospective case series and systematic review.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.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/mEvaluation and intervention for elevated ICP in spontaneous CSF leaks is associated with significantly improved success rates following primary endoscopic repair.4. Laryngoscope, 127:2011-2016, 2017.

Management of frontal sinus trauma includes coronal or direct open approaches through skin incisions to either ablate or obliterate the frontal sinus for posterior table fractures and openly reduce/internally fixate fractured anterior tables. The objective of this prospective case-series study was to evaluate outcomes of frontal sinus anterior and posterior table trauma using endoscopic techniques.Prospective evaluation of patients undergoing surgery for frontal sinus fractures was performed. Data were collected regarding demographics, etiology, technique, operative site, length involving the posterior table, size of skull base defects, complications, and clinical follow-up.Forty-six patients (average age, 42 years) with frontal sinus fractures were treated using endoscopic techniques from 2008 to 2016. Mean follow-up was 26 (range, 0.5 to 79) months. Patients were treated primarily with a Draf IIb frontal sinusotomies. Draf III was used in 8 patients. Average fracture defect (length vs width) was 17.1 × 9.1 mm, and the average length involving the posterior table was 13.1 mm. Skull base defects were covered with either nasoseptal flaps or free tissue grafts. One individual required Draf IIb revision, but all sinuses were patent on final examination and all closed reductions of anterior table defects resulted in cosmetically acceptable outcomes.Frontal sinus trauma has traditionally been treated using open approaches. Our findings show that endoscopic management should become part of the management algorithm for frontal sinus trauma, which challenges current surgical dogma regarding mandatory open approaches.