Clinical Focus

  • Cancer > Head and Neck Cancer
  • Otolaryngology
  • Chronic Rhinosinusitis
  • Endoscopic Sinus Surgery
  • Endoscopic Skullbase Surgery
  • Nasal Septum and Turbinate Surgery
  • Empty Nose Syndrome
  • Epiphora/Excessive Tearing Surgery
  • Epistaxis/Nosebleed Disorders and Surgery
  • Clivus/Foramen Magnum/Odontoid Surgery
  • All Varieties of Rhinologic/Sinus Disorders
  • Revision Nasal Airway and Sinus Surgery

Academic Appointments

  • Associate Professor - Med Center Line, Otolaryngology - Head & Neck Surgery Divisions
  • Associate Professor - Med Center Line (By courtesy), Neurosurgery
  • Member, Bio-X

Administrative Appointments

  • Co-Director, Rhinology Fellowship Training Program, Stanford Dept. of Otolaryngology (2011 - 2018)

Honors & Awards

  • Co-Valedictorian, Woodbridge High School, New Jersey (1988)
  • Baccalaureate with Honors, University of Pennsylvania (1992)
  • Stanley J. Sarnoff Endowment Medical Student Research Fellowship, Salk Institute, La Jolla, CA (1994)
  • Howard Hughes Medical Institute Medical Student Research Fellowship, U California, San Diego (1995)
  • American Heart Association Medical Student Research Fellowship, U Californioa, San Diego (1996)
  • M.D./Ph.D. Transfer Admission & Full Scholarship Award, University of Pittsburgh (1997)
  • Bernhard A. Goldman Prize in Dermatology, University of Pittsburgh (2003)
  • Gold Foundation “Little Apple” Medical Student Teaching Award Finalist, University of Pittsburgh (2004)
  • CORE Schering Plough Resident Research Award from the American Academy of Otolaryngology, University of Pittsburgh (2005)
  • Influenza virus tropism for human nasal epithelial cells of the upper airway, Marion Avery Family Grant (2012)
  • 2D and 3D Electron Microscopy Ultrastructure of Murine Nasal Cavity, Stanford Beckman Center Technology Innovation MiniGrant program (2012)
  • Immune Responses to Influenza Virus in Single Human Nasal Epithelial Cells, NIH/Cooperative Centers for Translational Research on Human Immunology and Biodefense (CCHI) (2012)
  • Human Mucosal Immune Responses to Influenza Virus: a Systems Biology Approach, NIH/Human Immunology Project Consortium (HIPC) (2012)
  • Career Development Award - Basal cells in maintenance and regeneration of the nasal epithelium, Triological Society of the American Academy of Otolaryngology-Head and Neck Surgery (2012)
  • National Finalist - Clinical Scientist Development Award, Doris Duke Charitable Foundation (December 2014)

Professional Education

  • Board Certification: Otolaryngology, American Board of Otolaryngology (2010)
  • Fellowship:University of Pennsylvania (2009) PA
  • Residency:University of Pittsburgh Medical Center (2008) PA
  • Internship:University of Pittsburgh Medical Center (2004) PA
  • M.D., Ph.D., University of Pittsburgh School of Medicine, MD - General Medicine PhD - Immunology (2003)
  • Medical Education:University of Pittsburgh School of Medicine (2003) PA
  • B.A., University of Pennsylvania, Neuroscience (1992)


  • Randall Kesten, Howard Levine, Thomas R. Jenkins, Jessica M. Liberatore and Jayakar V. Nayak. "United States Patent 9,433,347 Apparatus and ethmoid for treatment of ethmoid sinusitis", Sep 6, 2016

Current Research and Scholarly Interests

Upper Airway Stem Cell Biology, Fate, and Repair/Regeneration of the Airway Epithelium to treat Upper and Lower Airway Disorders

2019-20 Courses

Graduate and Fellowship Programs

All Publications

  • Environmental Triggers Associated With Empty Nose Syndrome Symptoms: A Cross-Sectional Study. The Annals of otology, rhinology, and laryngology Manji, J., Patel, V. S., Nayak, J. V., Thamboo, A. 2019: 3489419833714


    OBJECTIVES:: Empty nose syndrome (ENS) is thought to have multiple etiologies, one of which is a postsurgical phenomenon resulting from excessive loss of nasal tissues, particularly the inferior turbinate. Given that the inferior turbinate is instrumental in maintaining nasal homeostasis in different environments, it is believed that ENS symptoms arise only in more arid regions of the world. The aim of this study was to recruit an international population of individuals with ENS to investigate the association of local climate factors on the incidence and severity of ENS-specific symptoms.METHODS:: A cross-sectional study was performed of individuals from an international ENS database. ENS status was determined on the basis of a positive ENS questionnaire score (Empty Nose Syndrome 6-Item Questionnaire) and sinus computed tomographic imaging with supporting medical documentation. Participants completed a survey encompassing demographic, geographic, and symptom indicators. Climate variables were collected from global climate databases. Participant location was classified according to the Koppen-Geiger climate system. Pearson correlation analysis was performed using alpha = 0.05 to determine significance.RESULTS:: Fifty-three individuals with ENS were included. Participants were distributed across 5 continents and 15 countries (representing 4 distinct Koppen-Geiger zones). Although local climate factors varied significantly within this cohort, no significant association was found between Empty Nose Syndrome 6-Item Questionnaire symptom severity and these climate factors. However, most study participants reported exacerbation of their ENS symptoms in response to dry air (94%), air conditioning (64%), changes in season and weather (60%), and transitioning between indoors and outdoors (40%). This suggests that everyday local environmental factors may influence the well-being of these patients more than global, climate-level shifts.CONCLUSIONS:: ENS symptom severity does not appear to be related to climate or geographic factors. These findings deviate from the traditional dogma that ENS is experienced only in arid regions (or precluded in humid regions) and highlight the importance of recognizing this condition independent of geographic location.

    View details for PubMedID 30818962

  • Use of intranasal submucosal fillers as a transient implant to alter upper airway aerodynamics: implications for the assessment of empty nose syndrome. International forum of allergy & rhinology Borchard, N. A., Dholakia, S. S., Yan, C. H., Zarabanda, D., Thamboo, A., Nayak, J. V. 2019


    BACKGROUND: Empty nose syndrome (ENS) is a debilitating condition associated with inferior turbinate tissue loss. Surgical augmentation of the inferior meatus has been proposed to treat ENS, although efficacy data with validated, disease-specific questionnaires is limited. Instead we evaluated submucosal injection of a transient, resorbable filler into the inferior meatus to favorably alter nasal aerodynamics in ENS patients.METHODS: Patients with a history of inferior turbinate reduction, diagnosed with ENS via Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) and cotton testing, were enrolled and underwent submucosal injection of carboxymethylcellulose/glycerin gel (Prolaryn) into the inferior meatuses between July 2014 and May 2018. This material likely resorbs over several months. Outcomes included comparisons of preinjection and postinjection symptoms at 1 week, 1 month, and 3 months using the ENS6Q, 22-item Sino-Nasal Outcome Test (SNOT-22), Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9).RESULTS: Fourteen patients underwent injections. Mean ENS6Q scores significantly decreased from baseline at 1 week (20.8 vs 10.5; p < 0.0001), and remained reduced but upward-trending at 1 month (13.7, p = 0.002) and 3 months (15.5, p > 0.05) following injections. Mean SNOT-22 scores significantly decreased at 1 week (p = 0.01) and 1 month (p = 0.04), mean GAD-7 at 1 month (p = 0.02) and 3 months (p = 0.02), and mean PHQ-9 at 1 week (p = 0.01) and 1 month (p = 0.004) postinjection.CONCLUSION: Transient, focal airway bulking via submucosal filler injection at sites of inferior turbinate tissue loss markedly benefits ENS patients, suggesting that aberrant nasal aerodynamics from inferior turbinate tissue loss contributes to (potentially reversible) ENS symptoms.

    View details for PubMedID 30715801

  • The Horizon Sign and Frontal Bar: Two Topographic Landmarks to Confirm Endoscopic Frontal Sinusotomy. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Walgama, E. S., Thamboo, A., Tangbumrungtham, N., Ayoub, N., Patel, Z. M., Nayak, J. V. 2019: 194599818825472


    Confirming a thorough dissection of the frontal sinus during endoscopic sinus surgery can be challenging, and some surgeons would benefit from reliable topographic landmark identification to ensure completion of this sinus dissection. We defined (1) the "horizon sign" as the curvilinear shadow of the posterior table cast superiorly upon the anterior table of the frontal sinus at the acute angle of their meeting point and (2) the "frontal bar" as a sagittal septation at the union of the anterior/posterior tables. A cadaveric study, followed by an intraoperative consecutive case series, was performed to evaluate these 2 landmarks as indicators of complete dissection. The horizon sign was extremely reliable, identified in 100% of cadaveric frontal sinuses and intraoperative frontal sinuses. The frontal bar was present in only 67% of frontal sinuses by computed tomography. In live patients, the sensitivity and specificity of the frontal bar were 62% and 95%, respectively.

    View details for PubMedID 30691380

  • Microcurrent technology for rapid relief of sinus pain: a randomized, placebo-controlled, double-blinded clinical trial. International forum of allergy & rhinology Maul, X. A., Borchard, N. A., Hwang, P. H., Nayak, J. V. 2019


    BACKGROUND: Transcutaneous electrical nerve stimulation has proven to be effective in alleviating chronic pain from facial myalgias. We evaluated the efficacy of a novel handheld microcurrent-emitting device in short-term, office-based treatment of patients with sinus pain. This device, which is not yet U.S. Food and Drug Administration (FDA)-cleared, detects and treats regions corresponding to nerve fibers.METHODS: Randomized, double-blinded, placebo-controlled trial. Seventy-one participants with facial pain attributed to self-reported nasal/sinus disease were recruited from a tertiary rhinologic practice and the surrounding community and randomly assigned to either office-based use of an active (n = 38) or placebo (n = 33) microcurrent emitter. The study device was repetitively applied by each patient to the bilateral periorbital areas for 5 minutes. A visual analogue scale (VAS) for pain severity was administered before, and 10 minutes after, treatment.RESULTS: Active microcurrent-treated patients had a reduction in mean pain score from 5.63 pretreatment to 3.97 posttreatment (mean difference, 1.66; 95% confidence interval [CI], 1.20 to 2.12). Patients using the sham device also reported sinus pain reductions (mean difference, 0.91; 95% CI, 0.61 to 1.21). However, the active device demonstrated a significantly greater reduction in pain compared to sham (0.75-point difference, p = 0.007). Notably, 23.7% of patients using the active device had a reduction of 3 or more points by VAS compared to 0% of sham device patients (p = 0.003). One minor occurrence of transient facial skin erythema was noted.CONCLUSION: This trial suggests that treatment of rhinologic facial pain using this noninvasive microcurrent device is safe and effective in providing rapid relief of nasal/sinus pain. Additional studies with longer term follow-up are warranted.

    View details for PubMedID 30667597

  • Topical Corticosteroid Pretreatment Mitigates Cellular Damage After Caustic Injury to the Nasal Upper Airway Epithelium. American journal of rhinology & allergy Huang, Z., Velasquez, N., Nguyen, A., Ye, T., Le, W., Bravo, D. T., Hwang, P. H., Zhou, B., Nayak, J. V. 2019: 1945892418823305


    BACKGROUND: Topical corticosteroids are currently employed to reduce established airway inflammation; their prophylactic use might help limit cellular damage against harmful stimuli.OBJECTIVES: To determine the effects of a prophylactic topical application of budesonide (BD) on an in vivo nasal epithelium injury model induced by trichloroacetic acid (TCA).METHODS: C57Bl/6 mice were exposed to intranasal TCA topical application. Three groups received topical intranasal BD, saline solution, or no intervention prior to a single topical exposure to TCA. Controls were not exposed to TCA. Whole nasal cavity coronal sections were analyzed at 1, 3, and 6 days postinjury at tissue and cellular levels using histopathological analysis, immunofluorescent staining, and fresh tissue RNA microarray analysis.RESULTS: Prophylactic topical corticosteroid exposure protected the nasal epithelium from acute damage, maintaining epithelial thickness and cell survival. Six days following TCA exposure, epithelial and cellular changes were less pronounced on the BD-treated group compared to all exposure groups. The microarray analysis was used to evaluate the gene transcripts in all treatment groups. Ciliary tip protein, Sentan, and submucosal protein S100b were identified as potential factors in epithelial airway protection; immunofluorescent staining corroborated their presence and location within the respiratory epithelium.CONCLUSION: Topical corticosteroid treatment to the nasal epithelium can mitigate several of the early deleterious effects of acute epithelial damage in experimental airway injuries caused by TCA. These findings suggest a novel, direct cytoprotective effect of corticosteroids on the nasal epithelium, and the potential of expanding the use of prophylactic periprocedural topical corticosteroids for respiratory epithelial tissues.

    View details for PubMedID 30638033

  • Imaging predictors for malignant transformation of inverted papilloma. The Laryngoscope Yan, C. H., Tong, C. C., Penta, M., Patel, V. S., Palmer, J. N., Adappa, N. D., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2018


    OBJECTIVES/HYPOTHESIS: Inverted papillomas (IPs) are benign tumors of the sinonasal tract with a malignant transformation potential. Predicting the transformation propensity of IPs and corresponding risk factors has long been a challenge. In this study, we aimed to use radiographic findings on magnetic resonance imaging (MRI) and computed tomography (CT) to help differentiate IP from IP-transformed squamous cell carcinomas (IP-SCC).STUDY DESIGN: Retrospective cohort study.METHODS: A retrospective analysis was performed at two institutions comparing IP (n=76) and IP-SCC (n=66) tumors, evaluating preoperative radiographic imaging with corresponding surgical pathology reports. The presence of a convoluted cerebriform pattern (CCP) using postcontrast T1-weighted and T2-weighted MRI was evaluated. Using MRI diffusion-weighted imaging (DWI), we calculated the apparent diffusion coefficient (ADC) value of each tumor. We also determined the tumor origin, attachment sites, and presence of bony erosion using CT imaging.RESULTS: Benign IPs had a higher prevalence of CCP on MRI compared to IP-transformed SCC (P=.0001. The mean value ADC of malignant IP-SCC (ADCb0,1000 =1.12*10-3 mm2 /s) was significantly lower than that of benign IPs (ADCb0,1000 =1.49*10-3 mm2 /s, P=.002). IP-SCC tumors were more likely to be have orbital wall attachment (P=.002) and bony erosion (P<.0001) compared to IPs.CONCLUSIONS: Evaluation of CCP and DWI with ADC values on MRI are promising qualitative and quantitative methods to help differentiate benign IP tumors from their transformed malignant counterparts. Malignant IP-SCCs are associated with a loss of CCP and lower ADC values. Findings of orbital wall involvement and bony erosion on CT may also help determine presence of malignancy.LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

    View details for PubMedID 30515841

  • Precision medicine: why surgeons deviate from "appropriateness criteria" in the management of chronic rhinosinusitis and effects on outcomes. International forum of allergy & rhinology Thamboo, A., Rathor, A., Borchard, N. A., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2018


    BACKGROUND: In uncomplicated chronic rhinosinusitis (CRS), a consensus regarding appropriate medical therapy (AMT) before surgical intervention has been published in the form of "appropriateness criteria" for endoscopic sinus surgery (ESS). We sought to determine why tertiary surgeons may deviate from the suggested criteria and evaluated whether those deviations result in change in outcomes.METHODS: Patients with uncomplicated CRS were prospectively enrolled over the course of 1 year. The 22-item Sino-Nasal Outcomes Test (SNOT-22), a general health outcome out of 100, and a physician form, indicating management pathway and decision making, was completed at each visit over a 6-month follow-up period. A descriptive analysis was used to quantify reasons for veering from the "appropriateness criteria," and repeated linear regression modeling was used to measure whether compliance impacted SNOT-22, general health, and Lund-Kennedy (LK) scores over the period of study.RESULTS: One hundred fifty-five patients were enrolled. Sixty-eight percent followed the appropriate management pathway based on their presentation and the suggested criteria. Disparate reasons were documented for deviation in the other 32%, and, despite establishing several predictive categories, "other" was the most common reason, with various explanations well documented. SNOT-22, general health, and LK scores were not statistically impacted by compliancy status (p > 0.05).CONCLUSION: The suggested "appropriateness criteria" predict a management pathway for the majority of CRS patients. However, in a tertiary sinus center, surgeons may deviate from that model with a significant minority of their patients, for multiple reasons, without causing a change in outcomes.

    View details for PubMedID 29999595

  • The "Cross-court Draf IIb" Procedure for Advanced Nasal Septum or Frontal Sinus Pathology and Nasal Septum Pathology LARYNGOSCOPE Choby, G., Nayak, J. V. 2018; 128 (7): 1527–30

    View details for DOI 10.1002/lary.27016

    View details for Web of Science ID 000440007000018

  • Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling. International forum of allergy & rhinology Nayak, J. V., Rathor, A., Grayson, J. W., Bravo, D. T., Velasquez, N., Noel, J., Beswick, D. M., Riley, K. O., Patel, Z. M., Cho, D., Dodd, R. L., Thamboo, A., Choby, G. W., Walgama, E., Harsh, G. R., Hwang, P. H., Clemons, L., Lowman, D., Richman, J. S., Woodworth, B. A. 2018


    BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

    View details for PubMedID 29856526

  • The functional and psychological burden of empty nose syndrome INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Manji, J., Nayak, J. V., Thamboo, A. 2018; 8 (6): 707–12


    Empty nose syndrome (ENS) is a debilitating disorder thought to arise as a postsurgical phenomenon from excessive loss of nasal tissues. Affected patients often report a profound impact on all aspects of life, but the extent of this burden has not been quantified. We sought to determine the association of ENS with mental health and functional impairments.A cross-sectional study was performed of individuals with ENS recruited from online ENS forums. ENS status was validated based on a positive 6-item Empty Nose Syndrome Questionnaire (ENS6Q) score and sinus computed tomography imaging or supporting medical documentation. Subjects completed the ENS6Q, the 9-item Patient Health Questionnaire (PHQ-9) for depression, the 7-item Generalized Anxiety Disorder questionnaire (GAD-7), the Epworth Sleepiness Scale for daytime somnolence (ESS), the Work Productivity and Impairment questionnaire (WPAI), and the 5-dimension EuroQol General Health State Survey (EQ-5D-5L). Pearson correlation analysis was performed with α = 0.05 to determine significance.Fifty-three ENS individuals were included in the study. Overall, participants reported symptoms consistent with moderate anxiety (μ = 12.7; standard deviation [SD], 5.9) and moderately severe depression warranting treatment (μ = 17.9; SD, 6.8). Participants also noted a 62% reduction in productivity at work (n = 24) and 65% in all other activities (n = 53). ENS6Q symptom severity was correlated with more severe depression (p < 0.001), anxiety (p < 0.001), overall pain/discomfort (p = 0.002), and impairment in activities of daily living (p = 0.003).ENS individuals carry a clinically significant psychological burden and experience marked difficulties with many activities of daily living. A multimodal approach to address the tissue loss with surgery and cognitive-behavioral therapy for the psychological burden may provide the most optimal outcome.

    View details for PubMedID 29443458

  • Comparison of outcomes following culture-directed vs non-culture-directed antibiotics in treatment of acute exacerbations of chronic rhinosinusitis. International forum of allergy & rhinology Yan, C. H., Tangbumrungtham, N., Maul, X. A., Ma, Y., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2018


    BACKGROUND: Acute exacerbations in patients with chronic rhinosinusitis (CRS) are often treated with courses of systemic antibiotics. Poor correlation between microbiologic culture results and the sinus microbiome in CRS has caused increased debate as to the relevance of culture-directed antibiotics. There is currently sparse data comparing outcomes of culture-directed antibiotics vs non-culture-directed antibiotics for treatment of CRS.METHODS: This work reports a retrospective review. A total of 946 CRS patients treated with antibiotics were examined; 122 CRS patients with acute exacerbations were treated with culture-directed (n = 61) vs empiric (n = 61) antibiotics. Lund-Kennedy (LK) and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared pretreatment and posttreatment, with short-term (<1 month) and long-term (1-6 months) follow-up. Patient demographics, comorbidities, and prior surgical history were collected.RESULTS: Both groups had similar pretreatment SNOT-22 scores (p = 0.25) while the culture group had higher baseline LK endoscopy scores (p < 0.01). All data were adjusted for pertinent comorbidities, surgical history, co-therapeutics, and baseline scores. There was no difference in improvement in culture-directed and empirically treated groups in the short-term (p = 0.77) and long-term (p = 0.58) for minimal clinically important difference (MCID) of SNOT-22 and no difference in the short-term for LK scores (p = 0.11), but there was significantly more improvement in long-term LK scores in the culture-directed group (p = 0.01).CONCLUSION: Culture-directed therapy improves long-term endoscopy scores but does not yield an advantage in improving short-term endoscopy scores, nor in improving short-term and long-term quality of life scores in CRS patients. A prospective study is necessary to examine the relevance of routine microbiologic cultures in CRS patients.

    View details for PubMedID 29782068

  • Orbital Apex Syndrome NEW ENGLAND JOURNAL OF MEDICINE Borchard, N. A., Nayak, J. V. 2018; 378 (17): E23

    View details for PubMedID 29694826

  • Risk Stratification for Postoperative Venous Thromboembolism after Endoscopic Sinus Surgery OTOLARYNGOLOGY-HEAD AND NECK SURGERY Beswick, D. M., Vaezeafshar, R., Ma, Y., Hwang, P. H., Nayak, J. V., Patel, Z. M. 2018; 158 (4): 767–73


    Objectives Venous thromboembolism (VTE) contributes to significant patient morbidity, yet the incidence of VTE following endoscopic sinus surgery (ESS) is unknown. Quality improvement criteria are prompting increased standardization of perioperative VTE prophylaxis. Risk stratification for VTE may better define best practice measures to balance limiting VTE development with avoiding unnecessary chemoprophylaxis. Study Design Retrospective cohort study. Setting Tertiary institution. Subjects and Methods Adult patients who underwent ESS without perioperative chemoprophylaxis from 2008 to 2016 were evaluated. Identification of VTE was performed via screening diagnosis and procedure codes and clinical records, with subsequent confirmation of true-positive VTE. Data for individual Caprini scores were abstracted from electronic medical records. The primary outcome was development of VTE within 30 days following ESS relative to the Caprini score. Results A total of 2369 ESS cases were evaluated. While initial screening identified multiple potential VTE events, in-depth medical record review confirmed only 4 true VTE (0.17%). The VTE rate among cases with a Caprini score of <8 (0.09%, 2/2278) was significantly less ( P = .008) than the rate with a score of ≥8 (2.2%, 2/91). Beyond overall score, specific risk factors associated with development of postoperative VTE included stroke, central venous access, sepsis, and inpatient status (all P < .025), while prior VTE and hypercoagulability were not associated with postoperative VTE (all P > .5). Conclusions In the absence of perioperative chemoprophylaxis, postoperative VTE following ESS is extremely rare, particularly for patients carrying low-to-moderate Caprini scores. Risk stratification based on these data can assist in the design of VTE prophylaxis guidelines for ESS patients.

    View details for PubMedID 29460675

  • Glycolysis and the Hexosamine Biosynthetic Pathway as Novel Targets for Upper and Lower Airway Inflammation ALLERGY ASTHMA & IMMUNOLOGY RESEARCH Kim, Y., Nakayama, T., Nayak, J. 2018; 10 (1): 6–11


    Glycolysis is a process that rapidly converts glucose to lactate to produce adenosine triphosphate (ATP) under anaerobic conditions and occurs in all eukaryotic and prokaryotic cells. On the other hand, the hexosamine biosynthetic pathway (HBP) converts glucose to intermediate products like UDP-N-acetylglucosamine, which is critical for post-translational modifications of proteins, such as protein glycosylation. These 2 pathways are well known to contribute to glucose metabolism, but recent studies indicate modulation of these pathways can alter immune system function. In this review article, the authors present results suggesting how cellular metabolism, including glycolysis and the HBP, occurs in immune cells, and the immunologic significances of such activities. In addition, they provide a review of the literature on the effects of glycolysis and the HBP on various autoimmune, immunologic, and allergic diseases. Finally, the authors briefly introduce the results of their research on the immunologic effects of HBP supplementation (glucosamine) in animal models of allergic disease.

    View details for PubMedID 29178672

    View details for PubMedCentralID PMC5705485

  • Outcomes After Endoscopic Endonasal Resection of Craniopharyngiomas in the Pediatric Population WORLD NEUROSURGERY Patel, V. S., Thamboo, A., Quon, J., Nayak, J. V., Hwang, P. H., Edwards, M., Patel, Z. M. 2017; 108: 6–14
  • Enhanced Irrigant Delivery to the Ethmoid Sinuses Directly Following Ethmoid Punch Sinusotomy ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Abuzeid, W. M., Peterson, A. Z., Rathor, A., Xu, J. C., Velasquez, N., Rashan, A. R., Thamboo, A., Nayak, J. V. 2017; 126 (12): 804–12


    Ethmoid punch sinusotomy (EPS) is a feasible treatment for ethmoid sinusitis in a subset of chronic rhinosinusitis (CRS) patients per a recent report. This adjunctive work investigates the technical characteristics of EPS and determines if EPS measurably alters the topical delivery of irrigant into the ethmoid sinuses in a cadaveric model.The sinonasal cavities of 10 human cadaver heads were irrigated with a solution containing methylene blue and radio-opaque contrast prior to and following EPS. Procedural characteristics and irrigant distribution were assessed by endoscopy and computed tomography.Forty EPS procedures were performed through the ethmoid bulla and basal lamella. Compared to controls, EPS enhanced dye distribution into the anterior (90% vs 35%, P < .004) and posterior (90% vs 35%, P < .002) ethmoid sinuses, representing a 157% increase for each of these sites. Contrast was detected in a higher proportion of anterior (65% vs 5%, P < .001) and posterior (60% vs 0%, P < .001) ethmoid sinuses. Endoscopically guided catheter instillation of contrast through the EPS sites achieved radiotracer distribution throughout the ethmoid complex.Ethmoid punch sinusotomy sites can be reliably created via micro-minimally invasive procedures. Ethmoid punch sinusotomy improves irrigant delivery to the ethmoid sinuses, providing mechanistic understanding for the clinical outcomes observed in CRS patients.

    View details for PubMedID 29047295

  • Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Min, J., Nayak, J. V., Hulse, K. E., Stevens, W. W., Raju, P. A., Huang, J. H., Suh, L. A., Van Roey, G. A., Norton, J. E., Carter, R. G., Price, C. E., Weibman, A. R., Rashan, A. R., Ghosn, E. E., Patel, Z. M., Homma, T., Conley, D. B., Welch, K. C., Shintani-Smith, S., Peters, A. T., Grammer, L. C., Harris, K. E., Kato, A., Hwang, P. H., Kern, R. C., Herzenberg, L. A., Schleimer, R. P., Tan, B. K. 2017; 140 (6): 1562-+


    IgD is an enigmatic antibody isotype best known when coexpressed with IgM on naive B cells. However, increased soluble IgD (sIgD) levels and increased IgD+IgM- B-cell populations have been described in the human upper respiratory mucosa.We assessed whether levels of sIgD and IgD+ B cell counts are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B-cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels.sIgD levels were measured by means of ELISA in nasal tissues, nasal lavage fluid, sera, and supernatants of dissociated nasal tissues. IgD+ cells were identified by using immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by using real-time PCR and multiplex immunoassays. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records.sIgD levels and numbers of IgD+ cells were significantly increased in uncinate tissue (UT) of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with that of control subjects (4-fold, P < .05). IgD+ cells were densely scattered in the periglandular regions of UT from patients with CRSsNP. We also found that IgD+CD19+CD38bright plasmablast numbers were significantly increased in tissues from patients with CRSsNP compared with control tissues (P < .05). Among numerous factors tested, IL-2 levels were increased in UT from patients with CRSsNP and were positively correlated with tissue IgD levels. Additionally, supernatants of IL-2-stimulated dissociated tissue from patients with CRSsNP had significantly increased sIgD levels compared with those in IL-2-stimulated dissociated control tissue ex vivo (P < .05). Tissue from patients with CRS with preoperative antibiotic use or those with pathogenic bacteria showed higher IgD levels compared with tissue from patients without these variables (P < .05).sIgD levels and IgD+CD19+CD38bright plasmablast counts were increased in nasal tissue of patients with CRSsNP. IgD levels were associated with increased IL-2 levels and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhancement mucosal immunity or inflammation or respond to bacterial infections in patients with CRS, especially CRSsNP.

    View details for PubMedID 28625807

  • Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY Boeske, R., Vladar, E. K., Koennecke, M., Huesing, B., Linke, R., Pries, R., Reiling, N., Axelrod, J. D., Nayak, J. V., Wollenberg, B. 2017; 56 (5): 575-584


    The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and real time-quantitative polymerase chain reaction comparing gene expression in matched NPs and inferior turbinates revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B, and FZD2 were up-regulated and that FZD1, LRP5, LRP6, and WIF1 were down-regulated in NPs. Immunolabeling showed robust expression of Wnt ligands, nuclear β-catenin, and Axin-2 in NP tissue, suggesting that Wnt/β-catenin signaling is activated in NPs. We used primary human nasal epithelial cell (HNEpC) cultures to test the functional consequences of Wnt pathway activation. Monolayer HNEpCs treated with recombinant human WNT (rhWNT) 3A, but not with rhWNT4, had altered epithelial morphology and decreased adhesion, without loss of viability. We found that neither rhWNT3A nor rhWNT4 treatment induced proliferation. The expression and release of inflammatory cytokines IL-6 and granulocyte-macrophage colony-stimulating factor were increased after rhWNT3A exposure of HNEpCs. When differentiated at an air-liquid interface, rhWNT3A- and WNT agonist-, but not rhWNT4-treated HNEpCs, had abnormal epithelial architecture, failed to undergo motile ciliogenesis, and had defective noncanonical Wnt (planar cell polarity) signaling. On the basis of these results, we propose a model in which Wnt/β-catenin signaling sustains mucosal inflammation and leads to a spectrum of changes consistent with those seen during epithelial remodeling in NPs.

    View details for DOI 10.1165/rcmb.2016-0024OC

    View details for Web of Science ID 000400259400008

  • Defining surgical criteria for empty nose syndrome: Validation of the office-based cotton test and clinical interpretability of the validated Empty Nose Syndrome 6-Item Questionnaire. Laryngoscope Thamboo, A., Velasquez, N., Habib, A. R., Zarabanda, D., Paknezhad, H., Nayak, J. V. 2017


    The validated Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) identifies empty nose syndrome (ENS) patients. The unvalidated cotton test assesses improvement in ENS-related symptoms. By first validating the cotton test using the ENS6Q, we define the minimal clinically important difference (MCID) score for the ENS6Q.Individual case-control study.Fifteen patients diagnosed with ENS and 18 controls with non-ENS sinonasal conditions underwent office cotton placement. Both groups completed ENS6Q testing in three conditions-precotton, cotton in situ, and postcotton-to measure the reproducibility of ENS6Q scoring. Participants also completed a five-item transition scale ranging from "much better" to "much worse" to rate subjective changes in nasal breathing with and without cotton placement. Mean changes for each transition point, and the ENS6Q MCID, were then calculated.In the precotton condition, significant differences (P < .001) in all ENS6Q questions between ENS and controls were noted. With cotton in situ, nearly all prior ENS6Q differences normalized between ENS and control patients. For ENS patients, the changes in the mean differences between the precotton and cotton in situ conditions compared to postcotton versus cotton in situ conditions were insignificant among individuals. Including all 33 participants, the mean change in the ENS6Q between the parameters "a little better" and "about the same" was 4.25 (standard deviation [SD] = 5.79) and -2.00 (SD = 3.70), giving an MCID of 6.25.Cotton testing is a validated office test to assess for ENS patients. Cotton testing also helped to determine the MCID of the ENS6Q, which is a 7-point change from the baseline ENS6Q score.3b. Laryngoscope, 2017.

    View details for DOI 10.1002/lary.26549

    View details for PubMedID 28349563

  • Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids. Clinical immunology Edward, J. A., Sanyal, M., Le, W., Soudry, E., Ramakrishnan, V. R., Bravo, D. T., Nguyen, A. L., Zarabanda, D., Kingdom, T. T., Hwang, P. H., Garrison Fathman, C., Nayak, J. V. 2017; 179: 66-76


    Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (Treg) cells. Treg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of Treg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. Treg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced Treg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of Treg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically Treg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.

    View details for DOI 10.1016/j.clim.2017.02.002

    View details for PubMedID 28279811

  • Transseptal access with crossing multiple incisions for improved pedicle control and septum preservation: "How I do it" AMERICAN JOURNAL OF RHINOLOGY & ALLERGY Omura, K., Asaka, D., Nayak, J. V., Tanaka, Y. 2017; 31 (2): 139–41


    Recently, the surgical management of nasal tumors has been greatly influenced by advanced endoscopic techniques. To achieve complete endoscopic resection of large obstructing nasal tumors, a sufficient corridor for adequate exposure is also required. In the Japanese language, TACMI means "master expert," and herein we describe an endoscopic technique with novel elements that we term transseptal access with crossing multiple incisions (TACMI). This approach enables a direct transseptal approach to the pedicle through tumor transposition while allowing complete septal reconstruction and stability.We prospectively collected data from eight patients who underwent the TACMI approach for sinonasal tumors.When using TACMI, complete en bloc neoplasm resection was achieved in all but one patient, who underwent piecemeal tumor removal. The follow-up duration ranged from 10 to 28 months (mean, 19 months). None of the patients experienced septal perforation, nasal valve incompetence, or tumor recurrence.We presented evidence that TACMI was a simple, efficient, and effective technique for tumor transposition, and for pedicle visualization and access of challenging unilateral sinonasal lesions. These advantages contributed to limited blood loss, improved pedicle control, and complete nasal valve and septum preservation without functional deficits.

    View details for DOI 10.2500/ajra.2017.31.4416

    View details for Web of Science ID 000397976100014

    View details for PubMedID 28205501

  • Determinants and outcomes of upfront surgery versus medical therapy for chronic rhinosinusitis in cystic fibrosis. International forum of allergy & rhinology Ayoub, N., Thamboo, A., Habib, A., Nayak, J. V., Hwang, P. H. 2017


    The indications for surgical management of chronic rhinosinusitis (CRS) in patients with cystic fibrosis (CF) are poorly defined. In this study we compare outcomes of medical versus surgical treatment and examine trends associated with the transition from medical to surgical therapy in CF patients.One hundred thirty-six patients with CF referred to a tertiary rhinology practice were retrospectively divided into 3 cohorts: Medical, Upfront Surgery, or Crossover, if they converted from medical to surgical management. The 22-item Sino-Nasal Outcome Test (SNOT-22) and pulmonary function test (PFT) data were assessed up to 48 months.Compared to patients initially managed medically (n = 90), those who pursued upfront surgery (n = 46) had a greater incidence of nasal polyposis (p = 0.0011), prior sinus surgery (p = 0.0025), lower percent-predicted forced expiratory volume in 1 second (%FEV1 ) (p = 0.0063), and higher Lund-Mackay (p = 0.0025) and SNOT-22 (p = 0.0229) scores. Within the medical group, 35.5% converted to surgery after a mean of 14.3 months. Crossover (n = 32) was associated with a 6.1-point increase in SNOT-22 and a 4.5% deterioration in %FEV1 . Despite worsened symptom severity, the Crossover cohort ultimately achieved similar postoperative SNOT-22 scores (p = 0.831) and %FEV1 (p = 0.114) as those who underwent upfront surgery. Although the Medical cohort had the lowest baseline SNOT-22 scores (p < 0.001), surgery at any time normalized scores to the same baseline level (p = 0.652). Neither medical therapy nor surgery improved PFTs.Surgery effectively reduces CRS-related symptoms in CF patients but may not improve pulmonary function. In patients who first pursue medical therapy, symptomatic decline may prompt eventual conversion to surgery. Patients who delay surgery may achieve similar outcomes as those who pursue surgery upfront.

    View details for DOI 10.1002/alr.21912

    View details for PubMedID 28218486

  • Safe treatment of ethmoid sinusitis utilizing minimally invasive ethmoid punch sinusotomy (EPS) in chronic rhinosinusitis without polyposis (CRSsNP) patients. Laryngoscope Velasquez, N., Thamboo, A., Abuzeid, W. M., Nayak, J. V. 2017


    Current rhinologic practice is devoid of minimally invasive procedures dedicated to the treatment of ethmoid sinusitis to improve ventilation and topical drug delivery. We have recently described a handheld spiral punch to create minimally invasive ethmoid punch sinusotomy (EPS) sites into the ethmoid bulla and basal lamella, which significantly increased irrigant access to the ethmoid sinuses in cadaver models. Here, we conducted a clinical feasibility study to determine the initial safety evaluation of EPS in chronic rhinosinusitis without polyposis (CRSsNP) patients with active ethmoid disease.Single-arm, institutional review board-approved observational study.This study was performed in CRSsNP patients who failed medical management; were candidates for standard, traditional functional endoscopic sinus surgery; and were offered the option of EPS. EPS characteristics (patency, remucosalization) and complications (closure, mucus recirculation) were collected. Alterations in radiographic disease and symptoms after EPS were determined by Lund Mackay (LM) scoring and 22-item Sinonasal Outcome Test (SNOT-22) scoring, which was collected up to 6 months post-procedure.Thirty-two of 40 possible ethmoid compartments (17 of 20 anterior, 15 of 20 posterior) underwent EPS. Twenty-nine of 32 EPS sites remained patent (n = 29, 90.6%), with a minority displaying evidence of restenosis (n = 9, 28.1%) or closure (n = 3, 9.3%). All patent EPS sites had complete remucosalization (n = 29, 100%) with no evidence of mucus recirculation (n = 0, 0%) or other complications secondary to healing or device use. Ethmoid sinus cavities with a pre-EPS LM score of 1 or 2 universally improved to an LM score of 0 following EPS (n = 30 of 30, 100%). SNOT-22 scores significantly improved, with a mean reduction of 33.1 (49.6 ± 7.5 pre-EPS vs 16.5 ± 7.7 post-EPS, p < .0001).This feasibility study demonstrates that EPS appears to be a safe, minimally invasive procedure to treat ethmoid sinusitis in CRSsNP patients unresponsive to medical therapy that establishes ethmoid ventilation, and likely improves effective sinus irrigation. Conducting a clinical trial would be appropriate in assessing a potential role for EPS in the management of this condition.4. Laryngoscope, 2017.

    View details for DOI 10.1002/lary.26493

    View details for PubMedID 28194802

  • Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis. International forum of allergy & rhinology Patel, Z. M., Thamboo, A., Rudmik, L., Nayak, J. V., Smith, T. L., Hwang, P. H. 2017; 7 (2): 119-127


    The currently accepted treatment paradigm of treating chronic rhinosinusitis (CRS) first with appropriate medical therapy (AMT) and then with surgery if patients are refractory to AMT, has been criticized for lack of evidence. The objective of this study was to reassess the literature and establish the highest level of evidence possible regarding further management of CRS patients refractory to AMT.This study was a systematic review (SR) with meta-analysis (MA). Adult CRS patients who received AMT and then underwent either medical or surgical therapy in moderate to high level prospective studies were included. Outcomes assessed were disease-specific quality of life (QOL), nasal endoscopy, health-state utility, missed work days, change in cardinal symptoms of CRS, economic impact, and adverse events.A total of 970 manuscripts were identified; 6 studies were ultimately included in the SR with 5 included in the MA. Compared to continued medical therapy, endoscopic sinus surgery (ESS) significantly improved patient-based QOL scores (p < 0.00001) and nasal endoscopy scores (p < 0.00001). Difference in missed work days depended heavily on patient choice of intervention. Unpooled analysis showed improvements in olfaction, health utility scores, and cost-effectiveness.On meta-analysis, for CRS patients refractory to AMT, ESS significantly improves objective endoscopic scoring outcomes vs continued medical therapy alone. In patients with refractory CRS who have significant reductions in baseline QOL, ESS results in significant improvements. Continued medical therapy appears to maintain outcomes in patients with less severe baseline QOL. Unpooled analysis demonstrates improvement in health utility, olfaction, and cost-effectiveness following ESS compared to continued medical therapy alone, in medically refractory CRS.

    View details for DOI 10.1002/alr.21872

    View details for PubMedID 27863163

  • Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps. American journal of respiratory cell and molecular biology Böscke, R., Vladar, E. K., Könnecke, M., Hüsing, B., Linke, R., Pries, R., Reiling, N., Axelrod, J. D., Nayak, J. V., Wollenberg, B. 2017


    The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and real time-quantitative polymerase chain reaction comparing gene expression in matched NPs and inferior turbinates revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B, and FZD2 were up-regulated and that FZD1, LRP5, LRP6, and WIF1 were down-regulated in NPs. Immunolabeling showed robust expression of Wnt ligands, nuclear β-catenin, and Axin-2 in NP tissue, suggesting that Wnt/β-catenin signaling is activated in NPs. We used primary human nasal epithelial cell (HNEpC) cultures to test the functional consequences of Wnt pathway activation. Monolayer HNEpCs treated with recombinant human WNT (rhWNT) 3A, but not with rhWNT4, had altered epithelial morphology and decreased adhesion, without loss of viability. We found that neither rhWNT3A nor rhWNT4 treatment induced proliferation. The expression and release of inflammatory cytokines IL-6 and granulocyte-macrophage colony-stimulating factor were increased after rhWNT3A exposure of HNEpCs. When differentiated at an air-liquid interface, rhWNT3A- and WNT agonist-, but not rhWNT4-treated HNEpCs, had abnormal epithelial architecture, failed to undergo motile ciliogenesis, and had defective noncanonical Wnt (planar cell polarity) signaling. On the basis of these results, we propose a model in which Wnt/β-catenin signaling sustains mucosal inflammation and leads to a spectrum of changes consistent with those seen during epithelial remodeling in NPs.

    View details for DOI 10.1165/rcmb.2016-0024OC

    View details for PubMedID 28059551

  • Endoscopic Resection of Skull Base Teratoma in Klippel-Feil Syndrome through Use of Combined Ultrasonic and Bipolar Diathermy Platforms. Case reports in otolaryngology Edward, J. A., Psaltis, A. J., Williams, R. A., Charville, G. W., Dodd, R. L., Nayak, J. V. 2017; 2017: 6384586-?


    Klippel-Feil syndrome (KFS) is associated with numerous craniofacial abnormalities but rarely with skull base tumor formation. We report an unusual and dramatic case of a symptomatic, mature skull base teratoma in an adult patient with KFS, with extension through the basisphenoid to obstruct the nasopharynx. This benign lesion was associated with midline palatal and cerebral defects, most notably pituitary and vertebrobasilar arteriolar duplications. A multidisciplinary workup and a complete endoscopic, transnasal surgical approach between otolaryngology and neurosurgery were undertaken. Out of concern for vascular control of the fibrofatty dense tumor stalk at the skull base and need for complete teratoma resection, we successfully employed a tissue resection tool with combined ultrasonic and bipolar diathermy to the tumor pedicle at the sphenoid/clivus junction. No CSF leak or major hemorrhage was noted using this endonasal approach, and no concerning postoperative sequelae were encountered. The patient continues to do well now 3 years after tumor extirpation, with resolution of all preoperative symptoms and absence of teratoma recurrence. KFS, teratoma biology, endocrine gland duplication, and the complex considerations required for successfully addressing this type of advanced skull base pathology are all reviewed herein.

    View details for DOI 10.1155/2017/6384586

    View details for PubMedID 28133560

  • The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q): a validated 6-item questionnaire as a diagnostic aid for empty nose syndrome patients. International forum of allergy & rhinology Velasquez, N., Thamboo, A., Habib, A. R., Huang, Z., Nayak, J. V. 2017; 7 (1): 64-71


    Empty nose syndrome (ENS) is considered an acquired condition that remains difficult to diagnose objectively. Defining specific symptoms that can be reliably associated with this disorder would be essential to identifying possible ENS patients. We sought to validate an ENS-specific, 6-item questionnaire as an adjunct to the standard Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire to discriminate patients suspected of having ENS.The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) paired 6 common ENS symptoms (nasal suffocation, nasal burning, nasal openness, crusting, dryness, and impaired air sensation through nasal cavities) with testing on 75 patients divided in 3 patient cohorts: ENS; chronic rhinosinusitis without polyposis; and healthy controls. Participants answered 2 rounds of both the SNOT-22 questionnaire and ENS6Q within 48 hours of each other. No changes in treatments occurred in the test interval between questionnaires. Internal consistency, test-retest reliability, validity, and area under the curve were assessed to differentiate between patient cohorts using the 2 instruments.We found high internal consistency for ENS6Q and SNOT-22 questionnaire at 0.93 (95% CI, 0.90-0.95) and 0.94 (95% CI, 0.94-0.96), respectively. The test-retest reliability between timepoints for ENS6Q testing was 0.969. The ENS6Q statistically significantly discriminated between ENS and control patients and between ENS and chronic rhinosinusitis without polyposis (CRSsNP) patients, without significant differences between CRSsNP and controls. The area-under-the-curve (AUC) threshold score comparison further supported the ability of the ENS6Q to differentiate ENS from CRSsNP patients.The ENS6Q is the first validated, specific, adjunct questionnaire to the SNOT-22 to more reliably identify patients suspected of developing ENS.

    View details for DOI 10.1002/alr.21842

    View details for PubMedID 27557473

  • Peripheral blood T-helper cells and eosinophil populations in patients with atopic and nonatopic chronic rhinosinusitis AMERICAN JOURNAL OF RHINOLOGY & ALLERGY Huang, Z., Nayak, J. V., Sun, Y., Huang, Q., Zhou, B. 2017; 31 (1): E8-E12


    Analysis of recent research indicated that T-helper cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP).The purpose of this study was to investigate the peripheral blood Th1 and Th2 cells and eosinophil population in patients with CRS.Peripheral blood samples were obtained from nine nonatopic controls, 37 patients with CRSsNP, and 66 patients with CRSwNP. The samples were then analyzed by flow cytometry analysis (Th1 cell [CD4+, interleukin 4-, interferon γ+]; and Th2 cell [CD4+, interleukin 4+, interferon γ-]). The patients were stratified into four groups based on their allergic status by using skin-prick test results and immunoglobulin E level measurements as the following: (1) nonatopic CRSsNP, (2) nonatopic CRSwNP, (3) atopic CRSsNP, and (4) atopic CRSwNP. Eosinophil counts were also compared. The severity of nasal diseases in these patients was assessed via the Lund-Mackay score.No significant differences in peripheral blood Th1 and Th2 cells were found among all the atopic, nonatopic CRS groups, and the nonatopic control groups. Peripheral blood eosinophil levels in atopic CRSwNP were significantly elevated compared with the nonatopic controls (p < 0.05), but no significant difference was found among all atopic and nonatopic CRS groups.Analysis of our data demonstrated that a proportion of systemic Th1- and Th2-skewed lymphocytes in all CRS groups were similar to that in healthy subjects, irrespective of atopic status. The patients with CRSwNP and with atopy but not the patients with CRSsNP and with atopy demonstrated systemic eosinophilic inflammation. Further studies are needed to investigate underlying pathophysiologic mechanism or endotypes.

    View details for DOI 10.2500/ajra.2017.31.4405

    View details for Web of Science ID 000396471300006

  • Nose blowing after endoscopic sinus surgery does not adversely affect outcomes. The Laryngoscope Ayoub, N., Chitsuthipakorn, W., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2017


    Patients frequently are advised to abstain from nose blowing following endoscopic sinus surgery (ESS), despite a lack of evidence supporting this recommendation. This randomized study assessed whether nose blowing in the first postoperative week affects subjective and objective clinical outcomes.Forty patients undergoing ESS were randomized into an interventional arm in which patients blew their nose at least twice daily for the first 7 postoperative days, or a control arm in which patients refrained from nose blowing. All patients were allowed to blow their nose after 7 days. The frequency and degree of epistaxis was documented by daily diary and visual analog scale (VAS). At 1 and 4 weeks postoperatively, Nasal Obstruction Symptom Evaluation (NOSE) and Sino-Nasal Outcome Test-22 (SNOT-22) were collected, and endoscopies were recorded for blinded Lund-Kennedy scale scoring.There were no differences between the two groups in terms of frequency and duration of bleeding events, VAS epistaxis scores, SNOT-22 scores, and NOSE scores at every postoperative timepoint. Lund-Kennedy scores also were similar at the 1-week (P = 0.0762) and 4-week (P = 0.2340) postoperative visits, but the nose-blowing group had improved nasal discharge subscores at the first (P = 0.0075) and second (P = 0.0298) postoperative visits.Nose blowing after ESS does not appear to measurably improve symptoms of nasal congestion or general sinonasal quality of life, nor does it seem to adversely affect the frequency or severity of postoperative epistaxis during the first postoperative week. Judicious nose blowing may be permissible immediately after uncomplicated ESS.1b. Laryngoscope, 2017.

    View details for PubMedID 29068050

  • Barosinusitis: Comprehensive review and proposed new classification system. Allergy & rhinology (Providence, R.I.) Vaezeafshar, R., Psaltis, A. J., Rao, V. K., Zarabanda, D., Patel, Z. M., Nayak, J. V. 2017; 8 (3): 109–17


    Barosinusitis, or sinus barotrauma, may arise from changes in ambient pressure that are not compensated by force equalization mechanisms within the paranasal sinuses. Barosinusitis is most commonly seen with barometric changes during flight or diving. Understanding and better classifying the pathophysiology, clinical presentation, and management of barosinusitis are essential to improve patient care.To perform a comprehensive review of the available literature regarding sinus barotrauma.A comprehensive literature search that used the terms "barosinusitis," "sinus barotrauma," and "aerosinusitis" was conducted, and all identified titles were reviewed for relevance to the upper airway and paranasal sinuses. All case reports, series, and review articles that were identified from this search were included. Selected cases of sinus barotrauma from our institution were included to illustrate classic signs and symptoms.Fifty-one articles were identified as specifically relevant to, or referencing, barosinusitis and were incorporated into this review. The majority of articles focused on barosinusitis in the context of a single specific etiology rather than independent of etiology. From analysis of all the publications combined with clinical experience, we proposed that barosinusitis seemed to fall within three distinct subtypes: (1) acute, isolated barosinusitis; (2) recurrent acute barosinusitis; and (3) chronic barosinusitis. We introduced this terminology and suggested independent treatment recommendations for each subtype.Barosinusitis is a common but potentially overlooked condition that is primed by shifts in the ambient pressure within the paranasal sinuses. The pathophysiology of barosinusitis has disparate causes, which likely contribute to its misdiagnosis and underdiagnosis. Available literature compelled our proposed modifications to existing classification schemes, which may allow for improved awareness and management strategies for barosinusitis.

    View details for PubMedID 29070267

  • Equivalence in outcomes between Draf 2B vs Draf 3 frontal sinusotomy for refractory chronic frontal rhinosinusitis. International forum of allergy & rhinology Patel, V. S., Choby, G., Shih, L. C., Patel, Z. M., Nayak, J. V., Hwang, P. H. 2017


    Endoscopic Draf 2B and Draf 3 frontal sinusotomies are frequently performed for chronic refractory frontal rhinosinusitis. The purpose of this study was to compare outcomes between Draf 2B and Draf 3 procedures.A retrospective cohort study was conducted comparing patients undergoing bilateral Draf 2B vs Draf 3 procedures from 2000 to 2016. Patients with neoplasia, dysplasia, mucocele, cystic fibrosis, or ciliary dyskinesia were excluded. Preoperative disease parameters included number of prior surgeries, presence of polyps, preoperative 22-item Sino-Nasal Outcome Test (SNOT-22) score, frontal Lund-Mackay score, anterior-posterior diameter of the frontal ostium, and Global Osteitis Scoring Scale (GOSS). Postoperative outcomes included SNOT-22 score, neo-ostium patency, surgical revision rates, and complications.A total of 21 patients with bilateral Draf 2B and 17 patients with Draf 3 surgeries were compared. Mean follow-up time was 15.6 months. No significant differences were seen between groups for any preoperative disease parameter. Both cohorts showed statistically significant (p = 0.0001 [Draf 2B]; p = 0.0001 [Draf 3]) and clinically meaningful (Δ = 24.1; Δ = 24.9) improvements in SNOT-22 at last follow-up vs preoperatively. The Draf 2B group had greater improvement in SNOT-22 score than the Draf 3 group at 1 to 3 months (p = 0.003), but the magnitude of improvement equalized at 5 to 9 months (p = 0.66) and last follow-up (p = 0.90). No significant differences were noted between groups regarding patency, revision rates, or complications.Both Draf 2B and Draf 3 procedures offer durable symptomatic improvement for patients with refractory frontal CRS. The Draf 2B is associated with earlier postoperative symptom improvement and overall shows comparable long-term outcomes to the Draf 3 sinusotomy.

    View details for PubMedID 29131540

  • The prevalence of Eustachian tube dysfunction symptoms in patients with chronic rhinosinusitis. International forum of allergy & rhinology Tangbumrungtham, N., Patel, V. S., Thamboo, A., Patel, Z. M., Nayak, J. V., Ma, Y., Choby, G., Hwang, P. H. 2017


    While Eustachian tube dysfunction (ETD) is a known comorbidity of chronic rhinosinusitis (CRS), the prevalence of ETD symptoms in the CRS population is poorly understood. We sought to determine the cross-sectional prevalence of ETD in patients with CRS using the validated Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and to correlate ETDQ-7 scores with 22-item Sino-Nasal Outcome Test (SNOT-22) scores, endoscopy scores, and computed tomography (CT) scores.A total of 101 patients with confirmed CRS completed the ETDQ-7 and SNOT-22 at their initial visit to our rhinology clinic. Lund-Mackay CT and Lund-Kennedy endoscopy scores were also obtained. Spearman's correlation coefficient (ρ) was calculated.Among the 101 patients, 49 patients (48.5%) had an ETDQ-7 score of ≥14.5, signifying clinically significant ETD. The mean ± standard deviation (SD) ETDQ-7 score of the entire cohort was 17.8 ± 10.1. There was a moderately strong correlation between ETDQ-7 and the SNOT-22 ear subdomain (ρ = 0.691, p < 0.001). The correlation coefficient between ETDQ-7 and total SNOT-22 scores was ρ = 0.491 (p < 0.001), indicating moderate correlation. ETDQ-7 scores were poorly correlated to objective measures of sinonasal disease, including Lund-Mackay CT score (ρ = -0.055, p = 0.594) and Lund-Kennedy endoscopy score (ρ = -0.099, p = 0.334).Symptoms of ETD are highly prevalent among patients with CRS as documented by patient-reported outcome measures. The correlation between ETDQ-7 scores and SNOT-22 ear subdomain scores is moderately strong, while the correlation between ETDQ-7 scores and SNOT-22 scores is moderate. ETD severity does not correlate with CT score or nasal endoscopy score.

    View details for PubMedID 29227048

  • Distinguishing computed tomography findings in patients with empty nose syndrome. International forum of allergy & rhinology Thamboo, A., Velasquez, N., Ayoub, N., Nayak, J. V. 2016; 6 (10): 1075-1082


    Given the lack of basic diagnostic criteria for empty nose syndrome (ENS), we sought to define whether consistent radiographic characteristics could be identified to aid in the development of such criteria.Computed tomography (CT) scans were collected from 65 patients diagnosed with ENS, patients with a history of submucosal inferior turbinate reduction (ITR) without ENS, and patients without a history of sinonasal procedures. Measurements were taken at the level of the nasolacrimal duct, including the inferior turbinate (IT) mucosal thickness, and the widest distances between septum-IT, nasal floor-IT, lateral nasal wall-IT, and septum-lateral nasal wall. The thickest sites of soft tissue density of the nasal cavity floor, septum, and lateral wall were also measured in the anterior, central, and posterior segments of the nasal cavity.The mucosal thickness of both the central and posterior segments of the septum in ENS subjects was significant when compared to ITR without ENS (p < 0.01) and control subjects (p < 0.01). Constant landmarks such as the agger nasi, the presence of middle turbinate, and the nasolacrimal duct defined a simple set of landmarks that can serve as the start of the central-nasal region, and a cutoff >2.64 mm and >1.32 mm in the central nasal and posterior nasal regions provided the highest likelihood of differentiating ENS patients from ITR without ENS patients.These findings provide evidence there are 2 objective radiographic changes (central and posterior septal mucosa) that suggest ENS patients can be discriminated based on mucosal CT findings.

    View details for DOI 10.1002/alr.21774

    View details for PubMedID 27409044

  • Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation. JCI insight Vladar, E. K., Nayak, J. V., Milla, C. E., Axelrod, J. D. 2016; 1 (13)


    Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease.

    View details for PubMedID 27570836

  • Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Rashan, A. R., Goshn, E., Peterson, A., Yang, Y., Phillips, M., Sahaf, B., Herzenberg, L., Nayak, J. V. 2016; 6 (4): 378-384


    The immunologic mechanisms driving inflammation in the upper airways of patients with chronic rhinosinusitis (CRS) are poorly understood. Previous studies have shown that B cells and immunoglobulin E (IgE) levels are elevated in the nasal tissue of patients with atopic chronic rhinosinusitis without nasal polyps (CRSsNP). However, less is known regarding B cell subsets and IgE-producing plasmablasts in nonatopic CRSsNP patients.Human blood and ethmoid sinus mucosa samples were analyzed from control (n = 6) and nonatopic CRSsNP (n = 11) patients. Tissue samples were evaluated using high-dimensional flow cytometry.A population of IgE antibody secreting cells is significantly increased in situ within inflamed nasal tissue of nonatopic CRSsNP subjects when compared to control nasal tissue and the circulating peripheral blood (p < 0.05). This IgE plasma cell population displays ∼90% cell surface Ig lambda light chain, is mitotically active (Ki-67(+) ), and displays intracellular IgE expression. The predominant B cell population expressing IgE are plasmablasts (CD38(high) , CD138(-) ) not typically found in the blood or peripheral tissue of these patients.The nasal mucosa from nonatopic CRSsNP patients demonstrate a significant regional spike in resident in situ IgE plasmablast cells not seen in control nasal tissue or peripheral blood from the same patient. The restricted expression of Ig lambda light chain in this mitotically active IgE plasmablast population supports the hypothesis of aberrant B cell proliferation in the context of CRS. These findings suggest the presence of a unique regional immune microenvironment for B cell priming and/or selection within chronically inflamed airway tissues.

    View details for DOI 10.1002/alr.21696

    View details for Web of Science ID 000373618500007

    View details for PubMedID 26878990

  • Use of Pedicled Nasoseptal Flap for Pathologic Oroantral Fistula Closure. Journal of oral and maxillofacial surgery Noel, J. E., Teo, N. W., Divi, V., Nayak, J. V. 2016; 74 (4): 704 e1-6


    Oroantral fistula (OAF) is a pathologic, epithelialized communication between the oral cavity and the maxillary sinus. OAF most commonly results from posterior maxillary tooth or molar extraction owing to proximity of the dental roots to the maxillary antrum and the thinness of the adjacent antral floor. It also can arise secondary to implant and orthognathic surgeries, cyst and tumor removal, dental infection, trauma, or as a sequela of radiation therapy. Communications larger than 5 mm are less likely to heal spontaneously and can epithelialize, forming an OAF. When locoregional flaps and grafts are not ideal or have failed, but primary OAF closure is mandated, surgical options are unclear. This report describes a novel method for autologous tissue flap coverage from the nasal septum, pedicled off the posterior septal artery, for successful extension to, and closure of, OAFs.

    View details for DOI 10.1016/j.joms.2015.11.010

    View details for PubMedID 26704432

  • The nasal vestibular body: anatomy, clinical features, and treatment considerations EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Locketz, G. D., Teo, N. W., Walgama, E., Humphreys, I. M., Nayak, J. V. 2016; 273 (3): 777-781


    Nasal obstruction is a common presenting complaint, with many possible etiologies. Herein, we provide an introductory anatomic description, clinical relevance, and proposed nomenclature for an underappreciated soft tissue focus in the nasal vestibule-the nasal vestibular body (NVB)-that can contribute to nasal obstruction in a subset of patients. This is a small mound of dynamic soft tissue in the lateral aspect of the internal nasal valve, situated inferior and anterior to the head of the inferior turbinate that can be missed on routine examination for many salient reasons. In well-selected patients, whose symptoms of nasal obstruction may in part be secondary to the presence of this soft tissue focus, directed testing and tissue reduction can be performed.

    View details for DOI 10.1007/s00405-015-3868-2

    View details for Web of Science ID 000371063700035

    View details for PubMedID 26825801

  • International Consensus Statement on Allergy and Rhinology: Rhinosinusitis INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Orlandi, R. R., Kingdom, T. T., Hwang, P. H., Smith, T. L., Alt, J. A., Baroody, F. M., Batra, P. S., Bernal-Sprekelsen, M., Bhattacharyya, N., Chandra, R. K., Chiu, A., Citardi, M. J., Cohen, N. A., DelGaudio, J., Desrosiers, M., Dhong, H., Douglas, R., Ferguson, B., Fokkens, W. J., Georgalas, C., Goldberg, A., Gosepath, J., Hamilos, D. L., Han, J. K., Harvey, R., Hellings, P., Hopkins, C., Jankowski, R., Javer, A. R., Kern, R., Kountakis, S., Kowalski, M. L., Lane, A., Lanza, D. C., Lebowitz, R., Lee, H., Lin, S. Y., Lund, V., Luong, A., Mann, W., Marple, B. F., McMains, K. C., Metson, R., Naclerio, R., Nayak, J. V., Otori, N., Palmer, J. N., Parikh, S. R., Passali, D., Peters, A., Piccirillo, J., Poetker, D. M., Psaltis, A. J., Ramadan, H. H., Ramakrishnan, V. R., Riechelmann, H., Roh, H., Rudmik, L., Sacks, R., Schlosser, R. J., Senior, B. A., Sindwani, R., Stankiewicz, J. A., Stewart, M., Tan, B. K., Toskala, E., Voegels, R., Wang, D. Y., Weitzel, E. K., Wise, S., Woodworth, B. A., Wormald, P., Wright, E. D., Zhou, B., Kennedy, D. W. 2016; 6: S22-S209


    Isam Alobid, MD, PhD(1) , Nithin D. Adappa, MD(2) , Henry P. Barham, MD(3) , Thiago Bezerra, MD(4) , Nadieska Caballero, MD(5) , Eugene G. Chang, MD(6) , Gaurav Chawdhary, MD(7) , Philip Chen, MD(8) , John P. Dahl, MD, PhD(9) , Anthony Del Signore, MD(10) , Carrie Flanagan, MD(11) , Daniel N. Frank, PhD(12) , Kai Fruth, MD, PhD(13) , Anne Getz, MD(14) , Samuel Greig, MD(15) , Elisa A. Illing, MD(16) , David W. Jang, MD(17) , Yong Gi Jung, MD(18) , Sammy Khalili, MD, MSc(19) , Cristobal Langdon, MD(20) , Kent Lam, MD(21) , Stella Lee, MD(22) , Seth Lieberman, MD(23) , Patricia Loftus, MD(24) , Luis Macias-Valle, MD(25) , R. Peter Manes, MD(26) , Jill Mazza, MD(27) , Leandra Mfuna, MD(28) , David Morrissey, MD(29) , Sue Jean Mun, MD(30) , Jonathan B. Overdevest, MD, PhD(31) , Jayant M. Pinto, MD(32) , Jain Ravi, MD(33) , Douglas Reh, MD(34) , Peta L. Sacks, MD(35) , Michael H. Saste, MD(36) , John Schneider, MD, MA(37) , Ahmad R. Sedaghat, MD, PhD(38) , Zachary M. Soler, MD(39) , Neville Teo, MD(40) , Kota Wada, MD(41) , Kevin Welch, MD(42) , Troy D. Woodard, MD(43) , Alan Workman(44) , Yi Chen Zhao, MD(45) , David Zopf, MD(46) CONTRIBUTING AUTHOR AFFILIATIONS: (1) Universidad de Barcelona; (2) University of Pennsylvania; (3) Louisiana State University Health Sciences Center; (4) Universidade de São Paulo; (5) ENT Specialists of Illinois; (6) University of Arizona; (7) University of Oxford; (8) University of Texas; (9) University of Indiana; (10) Mount Sinai Beth Israel; (11) Emory University; (12) University of Colorado; (13) Wiesbaden, Germany; (14) University of Colorado; (15) University of Alberta; (16) University of Alabama at Birmingham; (17) Duke University; (18) Sungkyunkwan University; (19) University of Pennsylvania; (20) Universidad de Barcelona; (21) Northwestern University; (22) University of Pittsburgh; (23) New York University; (24) Emory University; (25) University of British Columbia; (26) Yale University School of Medicine; (27) Private Practice; (28) Department of Otolaryngology, Hôtel-Dieu Hospital, Centre de Recherche du Centre Hospitalier de l'Université de Montréal; (29) University of Adelaide; (30) Pusan National University; (31) University of California, San Francisco; (32) University of Chicago; (33) University of Auckland; (34) Johns Hopkins University; (35) University of New South Wales, Australia; (36) Stanford University; (37) Washington University; (38) Harvard Medical School; (39) Medical University of South Carolina; (40) Singapore General Hospital; (41) Taho University; (42) Northwestern University; (43) Cleveland Clinic Foundation; (44) University of Pennsylvania; (45) University of Adelaide; (46) University of Michigan.

    View details for DOI 10.1002/alr.21695

    View details for PubMedID 26889651

  • Inferior turbinate reconstruction using porcine small intestine submucosal xenograft demonstrates improved quality of life outcomes in patients with empty nose syndrome INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Velasquez, N., Huang, Z., Humphreys, I. M., Nayak, J. V. 2015; 5 (11): 1077-1081


    We describe the surgical technique for use of small intestine submucosal (SIS) xenograft implant for inferior turbinate reconstruction and report our early results in a pilot case series of patients suffering from symptoms consistent with empty nose syndrome (ENS).We report an observational prospective cohort study of ENS patients undergoing inferior turbinate reconstruction using porcine SIS xenograft. Effects of the procedure on quality of life (QOL) were assessed through serial 25-item Sino-Nasal Outcome Test (SNOT-25) scores and analyzed by 1-way analysis of variance (ANOVA) between the initial visit and 1, 4, and 12 weeks after surgery.Three patients with ENS underwent inferior turbinate reconstruction. No unexpected complications were noted over the 12-week follow-up course. Despite mild partial reabsorption of the SIS implant, neoturbinates were maintained in all patients. The mean preoperative score SNOT-25 was 77.6 (maximum 125). The mean postoperative scores were 65 at 1 week, 57 at 4 weeks, and 55 at 12 weeks (p < 0.01). Furthermore, for the "difficulty with nasal breathing" and "nose is too open" subdomains, statistically significant improvement was also noted at weeks 4 and 12 postoperatively (p < 0.05 and p <0.01, respectively).The use of porcine SIS xenograft for inferior turbinate reconstruction appears to be safe and effective in the treatment of patients diagnosed with ENS. This study demonstrates statistically significant improvement in global QOL metrics and nasal-specific subdomains following inferior turbinate reconstruction/neoturbinate creation for ENS as evaluated through serial SNOT-25 scores.

    View details for DOI 10.1002/alr.21633

    View details for Web of Science ID 000368004100016

  • Medical therapy vs surgery for recurrent acute rhinosinusitis. International forum of allergy & rhinology Costa, M. L., Psaltis, A. J., Nayak, J. V., Hwang, P. H. 2015; 5 (8): 667-673


    Treatment indications for recurrent acute rhinosinusitis (RARS) remain poorly defined. We studied outcomes of medical vs surgical treatment of RARS, anatomic variants associated with RARS, and factors predicting crossover from medical to surgical treatment.A total of 220 RARS patients treated between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only (MED); surgical only (SURG); or medical crossing over into surgical (CROSS). Twenty-two item Sino-Nasal Outcome Test (SNOT-22) scores, modified Lund-Kennedy endoscopy scores, and prevalence of anatomic variants by computed tomography (CT) were compared. A total of 220 CT scans obtained for non-sinus indications served as controls. A logistic regression model was used for analysis.The mean baseline SNOT-22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT-22 scores compared to the MED cohort at 3, 6, and 12 months follow-up (p < 0.0001). The crossover cohort converted to surgery after escalation of SNOT-22 score by a mean of 15 points (p < 0.03), and showed significant reduction postoperatively (p < 0.0001). Haller cell (odds ratio [OR] 3.9; p < 0.0001), concha bullosa (OR 3.7; p < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire RARS group vs controls; however, there were no inter-cohort differences in prevalence.RARS patients can benefit from both medical and surgical treatment strategies, but surgical treatment results in greater symptomatic improvement compared to medical treatment. Patients cross over from medical to surgical treatment when SNOT-22 scores escalate by a mean of 15 points. Haller cell, concha bullosa, and accessory ostium are associated with RARS but are equally common in medical, surgical, and crossover cohorts.

    View details for DOI 10.1002/alr.21533

    View details for PubMedID 25950995

  • Endoscopic Transnasal Approach for Urgent Decompression of the Craniocervical Junction in Acute Skull Base Osteomyelitis. Journal of neurological surgery reports Burns, T. C., Mindea, S. A., Pendharkar, A. V., Lapustea, N. B., Irime, I., Nayak, J. V. 2015; 76 (1): e37-42


    Ventral epidural abscess with osteomyelitis at the craniocervical junction is a rare occurrence that typically mandates spinal cord decompression via a transoral approach. However, given the potential for morbidity with transoral surgery, especially in the setting of immunosuppression, together with the advent of extended endonasal techniques, the transnasal approach could be attractive for selected patients. We present two cases of ventral epidural abscess and osteomyelitis at the craniocervical junction involving C1/C2 that were successfully treated via the endoscopic transnasal approach. Both were treated in staged procedures involving posterior cervical fusion followed by endoscopic transnasal resection of the ventral C1 arch and odontoid process for decompression of the ventral spinal cord and medulla. Dural repairs were successfully performed using multilayered, onlay techniques where required. Both patients tolerated surgery exceedingly well, had brief postoperative hospital stays, and recovered uneventfully to their neurologic baselines. Postoperative magnetic resonance imaging confirmed complete decompression of the foramen magnum and upper C-spine. These cases illustrate the advantages and low morbidity of the endonasal endoscopic approach to the craniocervical junction in the setting of frank skull base infection and immunosuppression, representing to our knowledge a unique application of this technique to osteomyelitis and epidural abscess at the craniocervical junction.

    View details for DOI 10.1055/s-0034-1395492

    View details for PubMedID 26251807

    View details for PubMedCentralID PMC4520966

  • Intraocular Pressure Changes in Emergent Surgical Decompression of Orbital Compartment Syndrome JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY Mohammadi, F., Rashan, A., Psaltis, A., Janisewicz, A., Li, P., El-Sawy, T., Nayak, J. V. 2015; 141 (6): 562-565


    Orbital compartment syndrome is an acute rise in intraorbital volume resulting in increased intraorbital pressure and possible ischemic compromise of the optic nerve. Tonometric pressure measurement of intraocular pressure can aid surgeons in the diagnosis of this condition and in choosing the need to proceed with emergent surgical intervention. In addition, we present an unexpected cause of orbital compartment syndrome following routine frontal sinus irrigation.An emergent lateral canthotomy and cantholysis followed by endoscopic medial wall decompression were performed, with intraocular pressure measurements performed throughout the evolution of this successful, and vision sparing, set of procedures. The techniques and continuous improvements in intraocular pressure measurements are described.There are only rare reports of the progression of intraocular pressure prior to, and concurrent with, surgical orbital decompression. While no absolute threshold for intraocular pressure exists for when surgical decompression should be performed, the decision of when and which decompression procedures to undertake should be based on clinical judgment and experience. Availability of tonometry in the operating room serves to measure response to management in these rare but challenging settings where intervention may be required to prevent irreversible visual loss.

    View details for DOI 10.1001/jamaoto.2015.0524

    View details for Web of Science ID 000356458300012

    View details for PubMedID 25880995

  • Clinical predictors of neo-osteogenesis in patients with chronic rhinosinusitis. International forum of allergy & rhinology Huang, Z., Hajjij, A., Li, G., Nayak, J. V., Zhou, B., Hwang, P. H. 2015; 5 (4): 303-309


    Neo-osteogenesis of the paranasal sinuses is a radiologic finding of unclear clinical significance. Although current evidence suggests that these bony changes represent an inflammatory response rather than an infectious osteitis, bacteria associated with the sinonasal mucosa may induce inflammatory mediators as a mechanism of neo-osteogenesis. The objectives of this study were (1) to determine whether there is an association between bacteria isolated on sinus culture and neo-osteogenesis, and (2) to identify other predictive factors for neo-osteogenesis.Ninety patients undergoing sinus surgery for medically refractory CRS were recruited. Radiologic evidence of neo-osteogenesis was assessed by the Global Osteitis Scoring Scale (GOSS) and mucosal disease severity was assessed by the Lund-Mackay score (LMS). Bacterial culture was obtained endoscopically at the preoperative office visit or during surgery. Multiple and logistic regression models were used to evaluate the association between the types of bacterial species isolated, number of previous surgeries, and severity of neo-osteogenesis.Thirty of the 90 (33.3%) patients had radiologic evidence of neo-osteogenesis. Pseudomonas aeruginosa was significantly associated with neo-osteogenesis (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.12 to 13.56), whereas Staphylococcus aureus was not. The number of previous surgeries, especially 2 or more previous surgeries, was associated with the extent of neo-osteogenesis (OR, 3.48; 95% CI, 1.14 to 10.51). The LMS was also significantly associated with the extent of neo-osteogenesis.The presence of P. aeruginosa in the sinuses is an independent predictor of neo-osteogenesis, whereas S. aureus is not. The number of previous surgeries and the LMS are also independently associated with the severity of neo-osteogenesis.

    View details for DOI 10.1002/alr.21485

    View details for PubMedID 25644047

  • Consistent ipsilateral development of the posterior extension of the quadrangular cartilage and bony spur formation in nasal septal deviation. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Saedi, B., Rashan, A. R., Lipan, M., Nayak, J. V., Most, S. P. 2015; 152 (3): 444-448


    Septal spurs are exceedingly common structural deformities that contribute to nasal obstruction and often require surgical correction. The posterior extension of the quadrangular cartilage (PEQC) and its relationship with septal spurs have not been previously examined. We seek to examine the anatomic and histologic relationship of the PEQC and concurrent septal spurs in patients undergoing septoplasty.Prospective cohort study.Facial plastic and rhinology center in tertiary hospital setting.Thirty patients with septal deviation are described in this series. The quadrangular cartilage and associated septal spur were removed en bloc from patients undergoing septoplasty. The length of the PEQC, the side of spur deviation, and the relationship of the PEQC to the spur (ipsilateral vs contralateral) were recorded.The mean length of the PEQC, beyond the bony-cartilaginous junction, was 30.06 ± 6.06 mm. The PEQC was present on the ipsilateral side of the spur deviation in all 30 patients (100%).At sites of septal spur formation, the quadrangular cartilage possesses an average 3-cm extension beyond its junction with the bony components of the septum. This cartilaginous extension is exclusively found on the same side of spur deviation. These findings have implications on our understanding of the ontogeny of commonly found septal spurs and deviations, as well as treatment strategies and cartilage graft harvesting.

    View details for DOI 10.1177/0194599814564549

    View details for PubMedID 25573678

  • Inverted Papilloma of the Sphenoid Sinus: Risk Factors for Disease Recurrence LARYNGOSCOPE Suh, J. D., Ramakrishnan, V. R., Thompson, C. F., Woodworth, B. A., Adappa, N. D., Nayak, J., Lee, J. M., Lee, J. T., Chiu, A. G., Palmer, J. N. 2015; 125 (3): 544-548


    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.Retrospective study.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.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).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.

    View details for DOI 10.1002/lary.24929

    View details for Web of Science ID 000349964100014

    View details for PubMedID 25418985

  • Complications associated with the pedicled nasoseptal flap for skull base reconstruction. Laryngoscope Soudry, E., Psaltis, A. J., Lee, K. H., Vaezafshar, R., Nayak, J. V., Hwang, P. H. 2015; 125 (1): 80-85


    To analyze complications associated with nasoseptal flap elevation and reconstruction in endoscopic skull base surgery.Case series.Retrospective chart review of all patients who underwent nasoseptal flap procedure in our institution between 2008 and 2013.A total of 121 patients were identified with a mean follow-up time of 10.4 months. Complications associated with this procedure occurred in 33 patients (27%). The majority of complications were related to the septal donor site and included septal perforation, cartilage necrosis, and prolonged crusting. Other complications included intraoperative injury to the flap pedicle (n = 4) or recurrent/persistent cerebrospinal fluid leak occurring in the early postoperative period (n = 7). Long-term quality-of-life data assessed via Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when compared to preoperative scores.The complication rate associated with nasoseptal flap elevation and inset is higher than previously described. The majority of complications became manifest beyond the immediate postoperative period and were associated with the septal donor site, including septal perforation, prolonged crusting, and cartilage necrosis. We hypothesize that donor site morbidity may be related to compromise of the contralateral septal vascular supply during the procedure. The range and frequency of complications of nasal septal flap surgery should be considered in counseling patients who may receive a nasoseptal flap for skull base reconstruction.4. Laryngoscope, 125:80-85, 2015.

    View details for DOI 10.1002/lary.24863

    View details for PubMedID 25111727

  • Long-term outcomes of endoscopic maxillary mega-antrostomy for refractory chronic maxillary sinusitis. International forum of allergy & rhinology Costa, M. L., Psaltis, A. J., Nayak, J. V., Hwang, P. H. 2015; 5 (1): 60-65

    View details for DOI 10.1002/alr.21407

    View details for PubMedID 25312656

  • The Combined Subtemporal-Transfacial Approach for the Resection of Juvenile Nasopharyngeal Angiofibromas With Intracranial Extension OTOLOGY & NEUROTOLOGY Kumar, A. R., Nayak, J. V., Janisiewicz, A. M., Li, G., Oghalai, J. S. 2015; 36 (1): 151-155


    Stage IVb juvenile nasopharyngeal angiofibromas (JNAs) are frequently regarded as unresectable because of their intracranial extension and cavernous sinus invasion. Although radiation has been described to control these tumors, it can leave the adolescent with long-lasting sequelae. Herein, we describe an alternative treatment strategy based on a combined subtemporal-transfacial surgical approach that permits the successful management of advanced stage JNAs by divorcing the intracranial vascular supply to these massive lesions.Four male patients were identified with Andrew's Stage IVB JNAs.All patients were treated by surgical resection using a combined subtemporal-transfacial surgical approach.Parameters assessed included tumor extent, number and types of surgical procedures, extent of resections, complications, and recurrence rate.Near-total tumor resections were achieved in all patients. No cerebrospinal fluid leak or cranial neuropathies were noted. All but one patient had local recurrences, and these could be managed with repetitive endoscopic debridement. No patient required adjuvant radiation treatment to control advanced disease.With the use of modern skull base surgical techniques, coordinated interdisciplinary care, and safe, near-total removal of the tumor mass, adolescent males with advanced JNAs may be spared the long-term morbidities associated with using radiation to treat these benign but aggressive lesions.

    View details for Web of Science ID 000346368200030

    View details for PubMedID 25036780

  • Air pollutants cause release of hydrogen peroxide and interleukin-8 in a human primary nasal tissue culture model. International forum of allergy & rhinology Cho, D., Le, W., Bravo, D. T., Hwang, P. H., Illek, B., Fischer, H., Nayak, J. V. 2014; 4 (12): 966-971


    A component of primary innate defense of the nasal mucosa against inhaled pathogens includes continuous, low-level release of hydrogen peroxide (H2 O2 ) into luminal secretions. Epidemiologically, an association exists between poor air quality and increased prevalence of sinonasal disease. To understand the effects of particulate matter (PM) in nasal mucosa, we studied the release of H2 O2 and interleukin 8 (IL-8) after PM exposure.Human nasal specimens were collected from surgery and cultured in serum-free growth medium. Cell integrity and recovery during culture was monitored by lactate dehydrogenase (LDH) release into the medium. Cultures were exposed to PM for 24 hours in the presence/absence of diphenyleneiodonium sulfate (DPI; a nicotinamide adenine dinucleotide phosphate [NADPH] oxidase inhibitor). Luminex cytokine and Amplex-Red H2 O2 assays were performed.LDH levels dropped rapidly within 2 days, indicative of stabilization and cell recovery after harvest. All cultures released H2 O2 into the medium. Exposure to PM (20 μg/cm(2) ) increased H2 O2 levels significantly (94.6 ± 7.7 nM) compared to untreated controls (55.8 ± 4.0 nM; p = 0.001). PM-induced H2 O2 production was partially inhibited by DPI (80.1 ± 3.8nM), indicating that cellular NADPH oxidase may be a primary source of H2 O2 production. Exposure to PM increased IL-8 levels in a dose-dependent fashion (control = 2301 ± 412 MFI; 20 μg/cm(2) = 5002 ± 1327 MFI; 40 μg/cm(2) = 8219 ± 1090 MFI; p = 0.022).PM increases the quantity of H2 O2 released by nasal epithelial cells, indicating that PM can contribute to oxidative stress in part by activating a normal cellular defense mechanism. Exposure to PM resulted in elevated IL-8 levels and mucin production in explants. Efforts to reduce airborne PM may lead to reduced H2 O2 and mucin production in sinonasal epithelium.

    View details for DOI 10.1002/alr.21413

    View details for PubMedID 25400124

  • A case of stereotactic radiation in skull base solitary fibrous tumor: more harm than good? Journal of neurological surgery reports Santa Maria, P. L., Abuzeid, W. M., Nayak, J. V., Chang, S. D., Blevins, N. H. 2014; 75 (2): e214-6


    Objective Due to its location, total resection of a skull base solitary fibrous tumor (SFT) can lead to morbidity with injury to lower cranial nerves, and a decision must be made between subtotal resection with possible stereotactic radiotherapy or total resection with cranial nerve morbidity. We report the long-term outcomes and review the literature of a case of stereotactic radiation in SFT to provide evidence for making this decision. Design A retrospective case review. Setting An academic tertiary referral center. Results We present a case with > 10 years follow-up of radiation following skull base SFT, initially misdiagnosed as schwannoma, where radiotherapy did not improve recurrence or metastatic behavior and led to complications during subsequent surgical resection. Conclusions SFT often masquerades as schwannoma, especially in the skull base. Careful immunohistochemistry, including CD34 expression, is critical to the diagnosis and management. This case highlights that total tumor resection of SFT remains the gold standard of treatment. Stereotactic radiation is not recommended in the management of skull base SFT.

    View details for DOI 10.1055/s-0034-1387196

    View details for PubMedID 25485216

    View details for PubMedCentralID PMC4242816

  • Long-term Sinonasal Outcomes of Aspirin Desensitization in Aspirin Exacerbated Respiratory Disease OTOLARYNGOLOGY-HEAD AND NECK SURGERY Cho, K., Soudry, E., Psaltis, A. J., Nadeau, K. C., McGhee, S. A., Nayak, J. V., Hwang, P. H. 2014; 151 (4): 575-581


    This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS).Case series with chart review.University hospital.A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization.Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted.Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD.

    View details for DOI 10.1177/0194599814545750

    View details for Web of Science ID 000342982900008

  • Anatomic relationship of nasolacrimal duct and major lateral wall landmarks: cadaveric study with surgical implications INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Ali, M. J., Nayak, J. V., Vaezeafshar, R., Li, G., Psaltis, A. J. 2014; 4 (8): 684-688


    Detailed knowledge of the surgical anatomic landmarks of the lateral nasal wall is important for safe and successful endoscopic sinonasal surgery. We sought to determine the relationship of major landmarks to the nasolacrimal duct (NLD).Twenty mid-sagittal head sections of 10 fresh frozen cadavers were studied after removal of the nasal septum. The insertion of the alar cartilage into the maxilla was taken as a fixed point and all measurements were performed in a defined axial plane at the level of the maxillary sinus natural ostium. Two surgeons independently recorded each measurement 3 times with an average of the readings used for statistical analysis.The overall agreement index was excellent (r = 0.84) between the observers. At the level of maxillary ostium, the mean distance from the alar rim to the NLD was 43.05 ± 4.76 mm on the right and 41.25 ± 4.56 mm on the left. The most anterior projection of the middle turbinate head was noted to be anterior to the NLD in 70% of specimens. In positional relationship, the maxillary line was posterior to the NLD in 55%, whereas the bulla ethmoidalis and the free edge of uncinate process were uniformly posterior to the NLD in all the specimens.This study provides useful anatomic and positional relationships between the NLD and major lateral wall landmarks. Although the maxillary line and the head of the middle turbinate are often considered useful guides to the position of the ipsilateral NLD, their spatial relationship to the NLD is not consistent. These landmarks, therefore, cannot be solely relied upon during surgery to avoid injury to the NLD.

    View details for DOI 10.1002/alr.21345

    View details for Web of Science ID 000340415400014

    View details for PubMedID 24845875

  • Outpatient endoscopic sinus surgery in cystic fibrosis patients: predictive factors for admission. International forum of allergy & rhinology Soudry, E., Mohabir, P. K., Miglani, A., Chen, J., Nayak, J. V., Hwang, P. H. 2014; 4 (5): 416-421


    An increasing number of adult patients with cystic fibrosis (CF) are becoming candidates for elective endoscopic sinus surgery (ESS). We sought to identify perioperative factors in this patient population that were predictive of postoperative admission.Retrospective chart review of CF patients who underwent ESS during the years 2005 through 2012. Multiple preoperative, intraoperative, and immediate postoperative variables were analyzed.Thirty-three patients who underwent 37 outpatient ESSs were identified. Successful same-day discharge was observed in 54%. In 46% of cases, postoperative admission was necessary, with a mean postoperative stay of 1.4 days. Pulmonary function, CF-related comorbidities, and history of lung transplant were not predictors of postoperative admission. Univariate analysis demonstrated that patients were more likely to be admitted if they had 1 of the following conditions: history of ≥4 prior ESS; procedure duration >2.5 hours; intraoperative blood loss greater than 150 mL; increased immediate postoperative pain scores; or larger narcotic requirements for pain control. On logistic regression analysis, a maximum pain score ≥ 7 out of 10 in the postanesthesia recovery unit was the only significant predisposing factor for postoperative admission.Although over 50% of adult CF patients can successfully undergo ESS on a same-day discharge basis, it is prudent to have contingent plans for potential inpatient observation postoperatively. Multivariate analysis suggests that preoperative demographics and pulmonary status cannot predict the need for postoperative admission, whereas higher pain scores in the postanesthesia care unit are predictive of the necessity for inpatient observation.

    View details for DOI 10.1002/alr.21285

    View details for PubMedID 24431198

  • Endoscopic reconstruction of surgically created skull base defects: a systematic review. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Soudry, E., Turner, J. H., Nayak, J. V., Hwang, P. H. 2014; 150 (5): 730-738


    To systematically review the literature concerning techniques of closure of endoscopically created skull base defects based on site of skull base defect and flow rate of cerebrospinal fluid (CSF).PubMed, SCOPUS, and Cochrane databases.A comprehensive systematic literature review.The literature search produced a total of 1708 studies. Of these, 1585 studies were excluded based on title and/or abstract review. A total of 123 articles remained for full-text review, 101 of which were subsequently excluded primarily because of lack of detailed information as to the reconstructive techniques used or clinical outcomes. Of the 22 studies remaining for final analysis, all were case series. A total of 673 patients were included in the analysis, with an overall postoperative CSF leak rate of 8.5%. Subgroup analysis was performed based on location of the skull base defect and presence and quality of intraoperative CSF leak.Based on level 4 evidence, in cases of low-flow intraoperative CSF leaks, skull base reconstruction with multilayered free grafts and synthetic materials offers similar outcomes to vascularized flaps. In cases of high-flow intraoperative CSF leaks, pedicled vascularized flaps appear to be superior. Location of the defect does not seem to be a significant factor in determining successful closure, with the exception of clival defects. In all other sites, good closure may be achieved by multiple reconstructive approaches. More consistency in data reporting and higher levels of evidence will ultimately be necessary to make definitive recommendations.

    View details for DOI 10.1177/0194599814520685

    View details for PubMedID 24493791

  • Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid. Neurosurgical focus Choudhri, O., Mindea, S. A., Feroze, A., Soudry, E., Chang, S. D., Nayak, J. V. 2014; 36 (3): E4-?


    Object In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. Methods Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. Results Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. Conclusions Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.

    View details for DOI 10.3171/2014.1.FOCUS13533

    View details for PubMedID 24580005

  • Human ethmoid sinus mucosa: a promising novel tissue source of mesenchymal progenitor cells STEM CELL RESEARCH & THERAPY Cho, K., Park, H., Roh, H., Bravo, D. T., Hwang, P. H., Nayak, J. V. 2014; 5


    The identification of new progenitor cell sources is important for cell-based tissue engineering strategies, understanding regional tissue regeneration, and modulating local microenvironments and immune response. However, there are no reports that describe the identification and isolation of mesenchymal progenitor cells (MPCs) from paranasal sinus mucosa, and compare the properties of MPCs between tissue sources within the sinonasal cavity. We report here the identification of MPCs in the maxillary sinus (MS) and ethmoid sinus (ES). Furthermore, we contrast these MPCs in the same individuals with MPCs from two additional head and neck tissue sources of the inferior turbinate (IT) and tonsil (T).These four MPC sources were exhaustively compared for morphology, colony-forming potential, proliferation capability, immunophenotype, multilineage differentiation potential, and ability to produce soluble factors.MS-, ES, IT-, and T-MPCs showed similar morphologies and surface phenotypes, as well as adipogenic, osteogenic, and chondrogenic differentiation capacity by immunohistochemistry and qRT-PCR for defined lineage-specific genes. However, we noted that the colony-forming potential and proliferation capability of ES-MPCs were distinctly higher than other MPCs. All MPCs constitutively, or upon stimulation, secrete large amounts of IL-6, IL-8, IL-10, IFN-γ, and TGF-β. After stimulation with TNF-α and IFN-γ, ES-MPCs notably demonstrated significantly higher secretion of IL-6 and IL-10 than other MPCs.ES-MPCs may be a uniquely promising source of MPCs due to their high proliferation ability and superior capacity toward secretion of immunomodulatory cytokines.

    View details for DOI 10.1186/scrt404

    View details for Web of Science ID 000331727700003

    View details for PubMedCentralID PMC4055077

  • Systemic prednisone administration selectively alters granulocyte subsets in nasal polyps from aspirin-exacerbated respiratory disease and chronic rhinosinusitis patients. International forum of allergy & rhinology Edward, J. A., Sanyal, M., Ramakrishnan, V. R., Le, W., Nguyen, A. L., Kingdom, T. T., Hwang, P. H., Nayak, J. V. 2013; 3 (11): 866-876


    Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients.NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining.Systemic prednisone administration was associated with a lower frequency of eosinophils (p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings.Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions.

    View details for DOI 10.1002/alr.21221

    View details for PubMedID 24106221

  • Characterization of human upper airway epithelial progenitors. International forum of allergy & rhinology Bravo, D. T., Soudry, E., Edward, J. A., Le, W., Nguyen, A. L., Hwang, P. H., Sanyal, M., Nayak, J. V. 2013; 3 (10): 841-847


    New epithelial cells are generated through the proliferation and differentiation of resident progenitor cells in the nasal cavity. In several upper airway diseases, such as cystic fibrosis and chronic rhinosinusitis, self-renewing progenitor cells may be functionally defective, or compromised in their ability, to regenerate cells that maintain normal mucociliary clearance. Herein, we describe our early work to define and characterize a rare population of human nasal epithelial putative progenitors.Single-cell suspensions of human ethmoid sinus tissues were prepared following endoscopic sinus surgery. Cell surface antibodies were analyzed as candidate markers for detecting progenitor cells. A panel of antibodies, including epithelial cell adhesion molecule (EpCAM, epithelial cells), CD45 (hematopoietic cells), nerve growth factor receptor (NGFR/CD271), intercellular adhesion molecule-1 (ICAM1/CD54), and integrin-α6 (ITGA6/CD49f) were used to resolve epithelial progenitor candidates by high-dimensional flow cytometry and the gating technique of fluorescence minus one (FMO) controls.A rare population of approximately 0.06% of total ethmoid cells was discriminated as EpCAM(-) CD45(-) NGFR(+) ICAM1(+) by surface markers. Use of ITGA6 was excluded based on FMO control analysis. This lineage-negative population was purified to 99% homogeneity by cell sorting and analyzed by immunofluorescence microscopy. Sorted cells were subsequently confirmed to uniformly express the transcription factor p63. Upon in vitro culture, lineage-negative clonal cells were confirmed to spontaneously differentiate into epithelial lineage-positive cells.Using the NGFR and ICAM1 cellular coordinates, we have identified a promising population of native human nasal epithelial progenitor cells that require more formal investigation for their role in upper airway regeneration.

    View details for DOI 10.1002/alr.21205

    View details for PubMedID 23901007

  • Expression of dual oxidases and secreted cytokines in chronic rhinosinusitis. International forum of allergy & rhinology Cho, D., Nayak, J. V., Bravo, D. T., Le, W., Nguyen, A., Edward, J. A., Hwang, P. H., Illek, B., Fischer, H. 2013; 3 (5): 376-383


    The airway epithelium generates reactive oxygen species (ROS) as a first line of defense. Dual oxidases (DUOX1 and DUOX2) are the H2 O2 -producing isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family in the airway epithelium. The purpose of this study was to explore the molecular expression, function, and regulation of DUOXs in chronic rhinosinusitis (CRS).Human nasal tissue samples and nasal secretions were collected from 3 groups of patients undergoing sinus surgery (normal, n = 7; CRS with polyposis [CRSwP], n = 6; CRS without polyposis [CRSsP], n = 6). Nasal secretions were studied for cytokine and H2 O2 content. Tissue samples were used to determine DUOX mRNA and protein expression.DUOX1 mRNA level (80.7 ± 60.5) was significantly increased in CRSwP compared to normal (2.7 ± 1.2) and CRSsP (2.3 ± 0.5, p = 0.042). DUOX2 mRNA levels were increased in both CRSwP (18.6 ± 9.9) and CRSsP (4.0 ± 1.3) compared to normal (1.1 ± 0.3; p = 0.008). DUOX protein was found in the apical portion of the nasal epithelium and protein expression was increased in CRSwP and CRSsP. H2 O2 production was significantly higher in CRSwP (160.9 ± 59.4 nM) and CRSsP (81.7 ± 5.6 nM) compared to normal (53.5 ± 11.5 nM, p = 0.032). H2 O2 content of nasal secretions correlated tightly with DUOX expression (p < 0.001). Cytokines (eotaxin, monokine-induced by interferon γ [MIG], tumor necrosis factor [TNF]-α, interleukin [IL]-8) showed significantly higher levels in nasal secretions from CRSwP compared to normal (p < 0.05). Levels of eotaxin, MIG, and TNF-α correlated closely with DUOX expression.DUOX1 and DUOX2 were identified as factors upregulated in CRS. Close correlations between DUOX expression and H2 O2 release, and correlation between key inflammatory cytokines and DUOX expression, indicate DUOX in the inflammatory response in CRS.

    View details for DOI 10.1002/alr.21133

    View details for PubMedID 23281318

  • Survival outcomes in acute invasive fungal sinusitis: A systematic review and quantitative synthesis of published evidence. Laryngoscope Turner, J. H., Soudry, E., Nayak, J. V., Hwang, P. H. 2013; 123 (5): 1112-1118


    Acute invasive fungal sinusitis (AIFS) is an aggressive and often fatal infection. Despite improvements in medical and surgical therapy, survival remains limited and the factors that contribute to patient outcomes remain poorly understood. The current study systematically reviews and quantitatively synthesizes the published literature to characterize prognostic factors associated with survival.Systematic review.Fifty-two studies comprising a total of 807 patients met inclusion criteria and were used for analysis of treatment, presentation, and outcomes. Univariate and multivariate logistic regression was used to identify prognostic factors.All studies were classified as level 4 evidence, as per definitions provided by the Oxford Center for Evidence-Based Medicine. The most common presenting symptoms of patients with AIFS were facial swelling (64.5%), fever (62.9%), and nasal congestion (52.2%). Most patients were treated with a combination of intravenous antifungal medication and surgery. The overall survival rate was 49.7%. On univariate analysis, poor prognosis was associated with renal/liver failure, altered mental status, and intracranial extension. Patients who were diabetic, had surgery, or received liposomal amphotericin B had an improved chance of survival. On multivariate analysis, advanced age and intracranial involvement were identified as independent negative prognostic factors. Positive prognostic factors again included diabetes and surgical resection.The overall mortality of patients with AIFS remains high, with only half of the patients surviving. Diabetic patients appear to have a better overall survival than patients with other comorbidities. Patients who have intracranial involvement, or who do not receive surgery as part of their therapy, have a poor prognosis.N/A.

    View details for DOI 10.1002/lary.23912

    View details for PubMedID 23300010

  • Trends in incidence and susceptibility among methicillin-resistant Staphylococcus aureus isolated from intranasal cultures associated with rhinosinusitis. American journal of rhinology & allergy Rujanavej, V., Soudry, E., Banaei, N., Baron, E. J., Hwang, P. H., Nayak, J. V. 2013; 27 (2): 134-137


    Reports regarding the incidence and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in rhinosinusitis (RS) are limited. This study was designed to identify epidemiology and trends of MRSA incidence and antimicrobial resistance in the sinonasal cavities.This is a retrospective case series. All intranasal/sinus cultures obtained by otolaryngologists at Stanford over a 20-year period (1990-2010) were retrospectively reviewed by mining the microbiology database. Nested searches were then made for all S. aureus and MRSA cultures. Patterns of incidence and changes in antibiotic susceptibilities were tabulated and statistical analysis was performed.Our search retrieved 10,387 positive intranasal culture samples, with S. aureus found in 800 (7.7%), and MRSA comprising 110 (1.06%) of this subset. Between the years of 1990 and 1999, only 2/112 (1.7%) of S. aureus-positive nasal cultures were positive for MRSA, with a sharp rise in incidence to 86/606 (14.2%) from 2000 to 2005, and to 22/82, 26.8% from 2006 to 2010. On a percent basis, using logistic regression modeling, this represents a statistically significant increasing trend (p < 0.0001) for MRSA sinusitis. However, over the 20-year interval studied, the patterns of antibiotic resistance among MRSA remained unaltered, especially with regard to trimethoprim-sulfamethoxazole and vancomycin.S. aureus and MRSA isolates from intranasal cultures, which were essentially absent before the year 2000, became significantly more common earlier this decade. These data show the increased role of MRSA in sinusitis. MRSA antibiotic susceptibilities have remained, however, largely stable during this time period.

    View details for DOI 10.2500/ajra.2013.27.3858

    View details for PubMedID 23562203

  • Low-frequency pulsed ultrasound in the nasal cavity and paranasal sinuses: a feasibility and distribution study INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Patel, Z. M., Hwang, P. H., Chernomorsky, A., Bravo, D. T., Nguyen, B. L., Nesterova, K., Nayak, J. V. 2012; 2 (4): 303-308


    Bacterial biofilms have been implicated in refractory rhinosinusitis. Biofilms have been shown to respond to treatment with low-frequency ultrasound (LFU) therapy in vitro, and exposure to LFU has shown efficacy in wound repair and topical drug delivery in other fields. This preliminary study was designed to evaluate the safety and feasibility of LFU for use in the nasal cavity and paranasal sinuses.This was an experimental observational study. Six cadaver heads were used to deliver a mixture of Renografin and methylene blue solvent to the paranasal sinuses via LFU both before and after resident endoscopic sinus dissection. Sinus computed tomography (CT) scans of the cadaver heads were performed before and after mixture delivery, and blinded assessments were made for distribution to individual sinuses. Mucosa was harvested from 2 subsites to evaluate LFU-treated cadaver tissue.Predissection, LFU delivered solution to 12 of 12 inferior and middle turbinates, 6 of 12 of the superior turbinates and ethmoid sinuses, and 1 of 12 maxillary sinuses as shown by contrast radiography. Postdissection, all heads showed delivery to the maxillary and sphenoid sinuses, with 8 of 12 sinus cavities showing delivery to the ethmoid region, and 4 of 11 to the frontal recess. Using hematoxylin and eosin (H&E) staining of tissue frozen sections, harvested tissue demonstrated no architectural damage to the mucosal layer from LFU exposure.LFU appears to be capable of reliably delivering topical solution to the turbinates and ethmoid region preoperatively and to all sinuses, except the frontal, postoperatively. The nasal epithelium does not appear to be disrupted histologically from LFU at this time and distance. This data provides a foundation for a prospective human protocol studying the efficacy of this modality in the treatment of patients with chronic rhinosinusitis and biofilm formation.

    View details for DOI 10.1002/alr.21039

    View details for PubMedID 22528624

  • Nationwide incidence of major complications in endoscopic sinus surgery INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Ramakrishnan, V. R., Kingdom, T. T., Nayak, J. V., Hwang, P. H., Orlandi, R. R. 2012; 2 (1): 34-39


    Endoscopic sinus surgery (ESS) is one of the most commonly performed procedures in otolaryngology. Major complications are estimated to occur in 1-3% of cases, based on early studies with relatively small patient cohorts in academic institutions. The aim of this study was to update data regarding major complication rates associated with ESS by analyzing a large patient database.Retrospective review of a nationwide database of patients who underwent ESS between 2003 and 2007. Major postoperative complications-cerebrospinal fluid (CSF) leak, orbital injury, and hemorrhage requiring blood transfusion-were identified by searching the database for related International Classification of Diseases, 9th edition (ICD-9) and Current Procedural Terminology (CPT) codes. Complication rates were examined and time to occurrence analyzed. Two-tailed test of proportions, global chi-square test, and logistical regression analysis were used for statistical comparison.A total of 62,823 patients who met rigorous inclusion criteria were included. The overall major complication rate was 1.00% (CSF leak 0.17%; orbital injury 0.07%; hemorrhage requiring transfusion 0.76%). CSF leak was less likely to occur in the pediatric population (p = 0.05), whereas orbital injury was more likely to occur in children (p < 0.001). Examination of the impact of image guidance (IGS) was limited by study design.The incidence of major complications associated with ESS appears to have decreased since early reports over 10 years ago. There may be different complication rates in the pediatric population. Study design limitations did not allow for comprehensive assessment of IGS in the development of these complications. These data help to educate otolaryngologists and patients about complication rates in ESS in a modern context.

    View details for DOI 10.1002/alr.20101

    View details for Web of Science ID 000308925100007

    View details for PubMedID 22311839

  • Sinonasal seromucinous hamartomas: Clinical features and diagnostic dilemma OTOLARYNGOLOGY-HEAD AND NECK SURGERY Figures, M. R., Nayak, J. V., Gable, C., Chiu, A. G. 2010; 143 (1): 165-166

    View details for DOI 10.1016/j.otohns.2009.11.014

    View details for Web of Science ID 000279262100029

    View details for PubMedID 20620639

  • Assessing the risk of irrigation bottle and fluid contamination after endoscopic sinus surgery 55th Annual Meeting of the American-Rhinologic-Society Lee, J. M., Nayak, J. V., Doghramji, L. L., Welch, K. C., Chiu, A. G. OCEAN SIDE PUBLICATIONS INC. 2010: 197–99


    Saline nasal irrigation has become an important aspect of post-operative care following endoscopic sinus surgery. The objective of this study was to identify the risks of contamination of both the nasal irrigation bottle and fluid following endoscopic sinus surgery.This was a prospective study of consecutive patients undergoing endoscopic sinus surgery for chronic sinusitis. All patients were given nasal irrigation bottles with detailed cleaning instructions preoperatively. Nasal irrigation bottles were collected and cultured at 1 and 2 weeks postoperatively. During the same visit, 5-ml of sterile normal saline was mixed into the irrigation bottle and then cultured separately.A total of 20 patients agreed to participate in the study. At 1 week postoperatively, 50% of the bottles had positive cultures with 40% of the irrigation samples testing positive for bacteria. At two weeks, the contamination in the irrigation bottle and fluid decreased to 26.7% and 20%, respectively. The most common bacteria cultured was Pseudomonas aeruginosa. There were no cases of postoperative infection.Despite detailed cleaning instructions, there is a relatively high risk of bacterial contamination in nasal irrigation bottles and fluid following endoscopic sinus surgery. Although these risks did not translate into higher infection rates postsurgery, it may be important for physicians to emphasize regular cleaning techniques to minimize a potential source of bacterial contaminant exposure.

    View details for DOI 10.2500/ajra.2010.24.3481

    View details for Web of Science ID 000278843200007

    View details for PubMedID 20537286

  • Biofilms in chronic rhinosinusitis: A review AMERICAN JOURNAL OF RHINOLOGY & ALLERGY Cohen, M., Kofonow, J., Nayak, J. V., Palmer, J. N., Chiu, A. G., Leid, J. G., Cohen, N. A. 2009; 23 (3): 255-260


    Bacterial biofilms consist of a complex, organized community of bacteria that anchor to both biotic and abiotic surfaces. They are composed of layers of embedded, live bacteria within extruded exopolymeric matrix. This configuration allows for evasion of host defenses and decreased susceptibility to antibiotic therapy while maintaining the ability to deliberately release planktonic bacteria, resulting in recurrent acute infections. Thus, bacterial biofilms were hypothesized to contribute to the progression and persistence of chronic rhinosinusitis.This review summarizes several of the seminal papers supporting this hypothesis.Multiple reports using various imaging modalities have demonstrated the presence of biofilms in sinonasal mucosa of patients with chronic rhinosinusitis. More recently, several studies have correlated the presence of biofilms with poor clinical outcomes in the disease process. Early therapeutic interventions have generated mixed results.Bacterial biofilms appear to contribute to the progression of chronic rhinosinusitis in a subset of patients, although substantial effort toward therapeutic intervention is still necessary.

    View details for DOI 10.2500/ajra.2009.23.3319

    View details for Web of Science ID 000266387300004

    View details for PubMedID 19490797

  • Head and neck epithelioid sarcoma in a child: Diagnostic dilemma and anterolateral thigh free flap reconstruction INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Nayak, J. V., Teot, L. A., Vyas, Y., Snyderman, C. H., Toh, E. H., Deleyiannis, F. W. 2008; 72 (5): 719-724


    The diagnostic dilemma is discussed of a child who presented with a granulomatous process of the external ear that was originally considered granuloma annulare and was later diagnosed as epithelioid sarcoma. We present the surgical treatment and the first report of reconstruction of a lateral skull base and cheek defect with an anterolateral thigh (ALT) free flap in a pediatric patient.

    View details for DOI 10.1016/j.ijport.2008.01.032

    View details for Web of Science ID 000255321200028

    View details for PubMedID 18346795

  • Head and Neck Cancer Immunotherapy: Clinical Evaluation CURRENT ONCOLOGY REPORTS Leibowitz, M. S., Nayak, J. V., Ferris, R. L. 2008; 10 (2): 162-169


    Overall survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has not improved appreciably over the past few decades. Because standard treatments have not controlled this disease with sufficiently high success rates, novel therapeutic approaches, such as immunotherapy, are under investigation. Cancer immunotherapy involves various techniques used to expand and activate the immune system to control tumor growth in vivo; to date, clinical evaluation has demonstrated low toxicity. An emerging form of SCCHN immunotherapy involves the use of antibodies that target growth factor receptors (where immune activation appears to enhance tumor lysis), resulting in improved clinical outcome. So far, immunotherapy appears to have the most applicability after other therapeutic interventions; however, its vast potential clinical value has yet to be fully explored. This article reviews immunotherapeutic strategies currently in clinical trials or under development for patients with SCCHN.

    View details for Web of Science ID 000207842200011

    View details for PubMedID 18377830

  • Deferring planned neck dissection following chemoradiation for stage IV head and neck cancer: The utility of PET-CT 110th Annual Meeting of the Triological-Society Nayak, J. V., Walvekar, R. R., Andrade, R. S., Daamen, N., Lai, S. Y., Argiris, A., Smith, R. P., Heron, D. E., Ferris, R. L., Johnson, J. T., Branstetter, B. F. WILEY-BLACKWELL. 2007: 2129–34


    To determine whether combined positron emission tomography and computed tomography (PET-CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC).Observational study of patients with de novo cervical > or =N2 regional spread of HNSCC in a tertiary care academic medical center.Forty-three patients were identified who underwent post-treatment PET-CT within 6 months of completing neoadjuvant chemotherapy combined with radiation therapy (CRT). The PET-CT was "positive" if the radiologist recommended tissue sampling or resection of cervical lymph nodes, or if there was progressive neck disease in the setting of distant metastatic disease. Patients who had positive PET-CT underwent confirmatory biopsy given clinical suspicion for regional cervical metastasis without distant disease. Patients with negative PET-CT were followed clinically and radiographically for a minimum of 5 months (median 18.1 months) after CRT.Ten (22%) of the 43 post-treatment PET-CT studies were positive. Seven of the 10 PET-CT scans (70% of positives) were true-positive given histologically-confirmed residual viable tumor or progressive disease including disease in the neck. The 3 remaining studies (30% of positives) were false-positive PET-CT results, given resolution of fluorodeoxyglucose (FDG) avidity on subsequent imaging or tissue sampling demonstrating absence of viable tumor cells. Of the 33 patients with negative PET-CTs in the neck, 1 patient had absence of FDG-avidity in the setting of malignant disease in the neck (3% false negatives); otherwise, patients with an initially negative PET-CT scan had no recurrences during the study (97% true negatives). This corresponds to a sensitivity of 87.5% (7/8), a specificity of 91% (32/35), a positive predictive value of 70% (7/10), a negative predictive value of 97% (32/33), and accuracy of 91% (39/43) for PET-CT scans in the detection of cervical metastatic disease after CRT. Overall, 37 (86%) of 43 patients were spared neck dissection using this technology without evidence of recurrent disease in the neck at extended follow-up.Our results suggest that planned neck dissection after CRT for HNSCC may be deferred in favor of serial PET-CT imaging, and that sampling of areas of suspicious FDG-avid uptake can be rationally considered prior to therapeutic neck dissection. These data also suggest that negative PET-CT scans are highly reliable for the absence of residual cervical nodal disease.

    View details for DOI 10.1097/MLG.0b013e318149e6be

    View details for Web of Science ID 000251397200008

    View details for PubMedID 17921898

  • Experience with the expanded endonasal approach for resection of the odontoid process in rheumatoid disease 52nd Annual Meeting of the American-Rhinologic-Society Nayak, J. V., Gardner, P. A., Vescan, A. D., Carrau, R. L., Kassam, A. B., Snyderman, C. H. OCEAN SIDE PUBLICATIONS INC. 2007: 601–6


    One of the common indications for removal of the odontoid process includes decompression of the cervicomedullary junction in patients with arthritic degeneration. Resection of the odontoid process can be accomplished using a completely transnasal endoscopic approach.A retrospective review was performed of patients with rheumatoid pannus undergoing transnasal endoscopic resection of the odontoid to assess preoperative characteristics, postoperative complications, and outcomes. Patients were followed for a minimum of 3 months in the postoperative period and/or until death. In addition to the primary procedure, those patients with preoperative cervical instability underwent posterior fusion of the upper cervical spine to the occiput for stabilization during the same hospitalization.Nine patients underwent transnasal endoscopic resection of the odontoid process for rheumatoid or degenerative pannus and brainstem compression. Perioperatively, four patients required a tracheostomy; two of whom had significant preoperative pharyngeal dysfunction. Two patients experienced postoperative velopharyngeal incompetence, which was transient. No patients had cerebrospinal fluid leaks, and there were no perioperative infectious complications noted. There was one delayed death in this patient cohort because of a presumed pulmonary embolus. Otherwise, all patients showed an improvement of their preoperative neurological symptoms.This early series of patients with rheumatoid pannus shows the feasibility of a fully endoscopic, completely transnasal approach for the resection of the odontoid process. Potential advantages include improved visualization, limited morbidity, decreased pain, and faster recovery than traditional approaches.

    View details for Web of Science ID 000250770000015

    View details for PubMedID 17999797

  • Phagocytosis induces lysosome remodeling and regulated presentation of particulate antigens by activated dendritic cells JOURNAL OF IMMUNOLOGY Nayak, J. V., Hokey, D. A., Larregina, A., He, Y., Salter, R. D., Watkins, S. C., Falo, L. D. 2006; 177 (12): 8493-8503


    Immunization with particulate Ag effectively induces antitumor and antiviral T cell-mediated immunity. Immature dendritic cells (DCs) efficiently internalize, process, and present a variety of particulate Ags; however, previously published data suggest that both the uptake of soluble Ag through micropinocytosis, and phagocytosis of particulates are significantly curtailed in activated DC populations. In this study, we demonstrate that although macropinocytosis of soluble Ag is diminished following DC activation, subsets of DCs in activated DC populations retain the ability to actively phagocytose particulate Ags. Live cell imaging of activated DCs reveals that phagocytosis of particulates can result in cytoskeletal remodeling and perinuclear lysosome cluster disruption in a time-dependent manner. Interestingly, our results suggest that in activated DC populations, presentation of phagocytosed particulate Ags is dependent on the nature of the activation signal. These results provide direct evidence of functional heterogeneity in DC populations and contribute to the development of particle-based immunization strategies.

    View details for Web of Science ID 000243416800026

    View details for PubMedID 17142747

  • Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL JOURNAL OF IMMUNOLOGY Lopez-Albaitero, A., Nayak, J. V., Ogino, T., Machandia, A., Gooding, W., DeLeo, A. B., Ferrone, S., Ferris, R. L. 2006; 176 (6): 3402-3409


    Squamous cell carcinoma of the head and neck (SCCHN) cells are poorly recognized in vitro by CTL despite expressing the restricting HLA class I allele and the targeted tumor Ag (TA). Several lines of evidence indicate that the lack of SCCHN cell recognition by CTL reflects defects in targeted TA peptide presentation by HLA class I Ag to CTL because of Ag-processing machinery (APM) dysfunction. First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-gamma-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin. Second, SCCHN cell recognition by CTL is restored by pulsing cells with exogenous targeted TA peptide. Third, the restoration of CTL recognition following incubation of SCCHN cells with IFN-gamma is associated with a significant (p = 0.001) up-regulation of the APM components TAP1, TAP2, and tapasin. Lastly, and most conclusively, SCCHN cell recognition by CTL is restored by transfection with wild-type TAP1 cDNA. Our findings may explain the association between APM component down-regulation and poor clinical course of the disease in SCCHN. Furthermore, the regulatory nature of the APM defects in SCCHN cells suggests that intralesional administration of IFN-gamma may have a beneficial effect on the clinical course of the disease and on T cell-based immunotherapy of SCCHN by restoring SCCHN cell recognition by CTL.

    View details for Web of Science ID 000238768400015

    View details for PubMedID 16517708

  • Current use of F-18-fluorodeoxyglucose positron emission tomography and combined positron emission tomography and computed tomography in squamous cell carcinoma of the head and neck LARYNGOSCOPE Zimmer, L. A., Branstetter, B. F., Nayak, J. V., Johnson, J. T. 2005; 115 (11): 2029-2034


    The history and physical examination, computed tomography (CT) and magnetic resonance imaging are the cornerstones for identifying new and recurrent cancers of the head and neck. The advent of positron emission tomography (PET) and combined PET/CT imaging technology is a promising development. These modalities have the potential to help stage patients presenting with head and neck cancer, identify responses to nonsurgical therapy, and allow earlier detection of recurrence in the hope of improving survival. The following paper provides a brief history of PET and PET/CT imaging. The current PET and PET/CT literature for squamous cell carcinoma of the head and neck is reviewed, and specific recommendations for its use are provided.

    View details for DOI 10.1097/01.MLG.0000181495.94611.A6

    View details for Web of Science ID 000233839600023

    View details for PubMedID 16319618

  • Diagnostic utility of positron emission tomography-computed tomography for predicting malignancy in cystic neck masses in adults LARYNGOSCOPE Ferris, R. L., Branstetter, B. F., Nayak, J. V. 2005; 115 (11): 1979-1982


    Combined positron emission tomography and computed tomography (PET-CT) is used for the diagnostic evaluation and staging of squamous cell carcinoma of the head and neck (SCCHN). By superimposing anatomic localization of CT with the physiologic data of PET, occult primary and metastatic neoplasms might be identified. Because the diagnostic algorithm for cystic neck masses in adults often overlaps with the work-up of cancer of unknown primary site, we evaluated the utility of PET-CT scans to identify the presence of malignancy and the location of primary tumor.Single-institution retrospective case review series.We reviewed the PET-CT imaging of cystic neck masses occurring in five patients over 40 years of age with significant risk factors for SCCHN and correlated this information with histopathology.In each patient in our series, the PET portion of a combined PET-CT was misleading, whereas the CT examination was more suggestive of the correct pathology. Ultimately, clinical judgment and endoscopic evaluation, guided by CT findings, were most valuable for distinguishing malignant versus benign processes and identifying the primary tumor sites.PET-CT may not be a reliable modality for identifying malignancy in adults with suspicious cystic neck masses. A thorough clinical evaluation by an experienced head and neck surgeon, in conjunction with contrast-enhanced CT, may be sufficient to facilitate the optimal management of such patients.

    View details for DOI 10.1097/01.mlg.0000178328.70288.55

    View details for Web of Science ID 000233839600014

    View details for PubMedID 16319609

  • Sensitization with xenogeneic tissues alters the heavy chain repertoire of human anti-Ga1 alpha 1-3Ga1 antibodies TRANSPLANTATION Yu, P. B., Parker, W., Nayak, J. V., Platt, J. L. 2005; 80 (1): 102-109


    Antigen sensitization alters the use of genes encoding the variable and constant regions of immunoglobulin, changing avidity, and function. Alterations in variable region genes induced by carbohydrate antigens have been studied extensively in animals but are incompletely characterized in humans. We asked how sensitization with the carbohydrate Galalpha1-3Gal modifies antibody heavy chain use.To overcome limited access to B cells, we analyzed anti-Galalpha1-3Gal antibodies from the serum of naïve and sensitized human subjects with anti-sera specific for VH families.We find that in preimmune subjects, heavy chains of IgM anti-Galalpha1-3Gal derived primarily from VH3 family members, whereas the heavy chains of IgG are from diverse VH families. After sensitization, heavy chains of IgM and IgG antibodies both derived from diverse VH families.The preimmune repertoire of IgM antibodies to Galalpha1-3Gal is thus more restricted than the antibody repertoire after sensitization, suggesting an antigen-induced shift in the repertoire.

    View details for DOI 10.1097/01.TP.0000163976.07023.6D

    View details for Web of Science ID 000230473800018

    View details for PubMedID 16003240

  • Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses MOLECULAR THERAPY DiLeo, J., Banerjee, R., Whitmore, M., Nayak, J. V., Falo, L. D., Huang, L. 2003; 7 (5): 640-648


    Vaccination with antigenic peptides encoding tumor antigens has the potential to be an effective treatment for cancer. To induce tumor-specific cellular immune responses, a peptide antigen must be presented by antigen-presenting cells (APCs) to T-cells in the lymphatic tissues. Effective in vivo delivery of peptide antigens to APCs has been problematic. Here we use a model antigen from the HPV16 E7 protein to formulate LPD/E7 particles that upon iv administration are internalized by CD11c(+) and CD11b(+) cells in the marginal zone of the spleen. Either iv or sc vaccination with LPD/E7 particles induces E7-specific CTL responses stronger than those obtained using previously described liposome/peptide strategies and prevents the establishment of E7-expressing tumors. Furthermore, the administration of LPD/E7 particles to tumor-bearing mice caused complete tumor regression in 100% of the treated animals. Based on these studies, the entrapment of peptide antigens inside LPD particles may be an effective and generally applicable strategy for the enhancement of peptide vaccine potency.

    View details for DOI 10.1016/S1525-0016(03)00064-9

    View details for Web of Science ID 000182645800012

    View details for PubMedID 12718907

  • Myoepithelial neoplasia of the submandibular gland - Case report and therapeutic considerations ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Nayak, J. V., Molina, J. T., Smith, J. C., Branstetter, B. F., Hunt, J. L., Snyderman, C. H. 2003; 129 (3): 359-362


    Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.

    View details for Web of Science ID 000181522400016

    View details for PubMedID 12622550

  • Primary lymphoma of the larynx: New diagnostic and therapeutic approaches ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES Nayak, J. V., Cook, J. R., Molina, J. T., Branch, M. P., Branstetter, B. F., Ferris, R. L., Myers, E. N. 2003; 65 (6): 321-326


    Tumors primary in the larynx, when not of squamous cell origin, require special diagnostic and therapeutic attention. An unexpected case of non-Hodgkin's lymphoma localized in the larynx in a patient with a brief history of dysphagia and hoarseness is discussed. This supraglottic tumor was extensively characterized at our institution for morphologic features by microlaryngoscopy, histology, immunocytochemical profiles with flow cytometry, chromosomal aberrations using banded karyotyping and extent of disease via PET-CT imaging. Our detailed analysis distinguished this neoplasm as a new-onset diffuse large B cell laryngeal lymphoma rather than a mucosa-associated lymphoid tissue lymphoma. A rational diagnostic approach guided the combination chemotherapy/immunotherapy treatment strategy instead of traditional localized radiation therapy. These findings highlight the importance of a thorough phenotypic and cytogenetic characterization of head and neck neoplasms, which has implications for downstream diagnostic considerations, interventional strategies and the available therapeutic options. The presence of nonsquamous laryngeal tumors reinforces the dictum to obtain a reliable tissue diagnosis before initiating definitive therapy.

    View details for DOI 10.1159/000076049

    View details for Web of Science ID 000189170500003

    View details for PubMedID 14981324

  • Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo HUMAN GENE THERAPY He, Y. K., Pimenov, A. A., Nayak, J. V., Plowey, J., Falo, L. D., Huang, L. 2000; 11 (4): 547-554


    The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs. Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 microg/ml and remained above 1 microg/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12. The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively. These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.

    View details for Web of Science ID 000085659100004

    View details for PubMedID 10724033

  • The dual phases of the response to neonatal exposure to a V-H family-restricted staphylococcal B cell superantigen JOURNAL OF IMMUNOLOGY Silverman, G. J., Nayak, J. V., Warnatz, K., Hajjar, F. F., Cary, S., Tighe, H., Curtiss, V. E. 1998; 161 (10): 5720-5732


    In vitro studies of several naturally occurring proteins have characterized VH family-specific B lymphocyte binding and stimulatory properties that appear analogous to those of T cell superantigens. To examine the in vivo consequences of exposure to a putative B cell superantigen, we treated neonatal BALB/c mice with a form of staphylococcal protein A (MS) devoid of Fcgamma binding activity, which retains the clan VHIII Fab binding specificity. In naive adults, about 5% of peripheral B cells and >13% of splenic IgM-secreting cells display MS binding activity, in association with high IgM and low IgG circulating anti-MS Ab titers. Neonatal exposure to MS elicited two distinct temporal phases of immune responsiveness. The early phase, representing the first approximately 5 wk of life, was associated with MS-specific B cell and T cell tolerance. Microfluorometric assays revealed that exposure caused a dramatic MS-specific B cell clonal loss in bone marrow and spleen, but levels normalized by about 3 wk of life. The late phase (>6 wk of age) was associated with spontaneous priming for MS-specific T cell responses and production of MS-specific IgG1 Abs despite long term persistently depressed in vivo and in vitro MS-specific IgM responses. In vivo challenge during the late phase induced high frequencies of MS-specific IgG-secreting cells, indicating recruitment of highly focused Ab responses that were predominantly encoded by rearrangements of the S107 family, a member of the VHIII clan. These studies document the immunodominance of the VH-restricted Fab binding site on staphylococcal protein A and demonstrate the diverse effects of a B cell superantigen on the emerging peripheral B cell compartment.

    View details for Web of Science ID 000076919100079

    View details for PubMedID 9820554

  • In vivo consequences of B cell superantigen immunization Conference on B Lymphocytes and Autoimmunity Silverman, G. J., Nayak, J. V., Wagenknecht, R., Warnatz, K. NEW YORK ACAD SCIENCES. 1997: 105–110

    View details for Web of Science ID A1997BH93X00009

    View details for PubMedID 9186643

  • B-cell superantigens: molecular and cellular implications. International reviews of immunology Silverman, G. J., Nayak, J. V., La Cava, A. 1997; 14 (4): 259-290


    B cell superantigens are proteins that are capable of immunoglobulin variable region mediated binding interactions with the naive B cell repertoire at frequencies that are orders of magnitude greater than occur for conventional antigens. Within this review we discuss recent observations regarding the molecular basis of these interactions and the distribution of superantigen binding capacities in different human B cell populations. These findings and current predictions regarding the relevance of these proteins to the physiologic development of immune repertoires are also discussed.

    View details for PubMedID 9186781