Jayakar V. Nayak, MD, PhD

All Publications

• The Temporoparietal Fascia Flap Transposition Technique for Ventral Skull Base Reconstruction: Anatomic Analysis and Surgical Application. Operative neurosurgery (Hagerstown, Md.) Xu, Y., Asmaro, K., Mohyeldin, A., Nunez, M. A., Mao, Y., Cohen-Gadol, A. A., Nayak, J., Fernandez-Miranda, J. C. 2024

  Abstract

  BACKGROUND AND OBJECTIVES: The temporoparietal fascia (TPF) flap is an alternative for revision endoscopic skull base reconstruction in the absence of the nasoseptal flap, and we aimed to investigate the anatomy and surgical application of TPF flap transposition in endoscopic endonasal surgery.METHODS: Six lightly embalmed postmortem human heads and 30 computed tomography angiography imaging scans were used to analyze the anatomic features of the TPF flap transposition technique. Three cases selected from a 512 endoscopic endonasal cases database were presented for the clinical application of the TPF flap.RESULTS: The TPF flap, composed by the deepest 3 scalp layers (galea aponeurotica, loose areolar connective tissue, and pericranium), can be harvested and then transposed through the infratemporal-maxillary-pterygoid tunnel to the ventral skull base. The superficial temporal artery as its feeding artery, gives frontal and parietal branches with similar diameter (1.5 ± 0.3 mm) at its bifurcation. The typical bifurcation was present in 50 sides (83.3%), with single (frontal) branch in 5 sides (8.3%), single (parietal) branch in 2 sides (3.3%), and multiple branches (>2) in 3 sides (5%). The transposed TPF flap was divided into 3 parts according to its anatomic location: (1) infratemporal part with an area of 19.5 ± 2.5 cm2, (2) maxillary part with an area of 23.7 ± 2.8 cm2, and (3) skull base part with an area of 44.2 ± 4 cm2. Compared with the nasoseptal flap, nasal floor flap, inferior turbinate flap, and extended septal flap, the coverage area of the skull base part of the TPF flap was significantly larger than any of them (P < .0001).CONCLUSION: The TPF flap technique is an effective alternative for endoscopic endonasal skull base reconstruction. The TPF flap could successfully cover large skull base defects through the infratemporal-maxillary-pterygoid tunnel.

  View details for DOI 10.1227/ons.0000000000001048

  View details for PubMedID 38189439

• Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy. International forum of allergy & rhinology Miller, J. E., Taylor-Cousar, J. L., Overdevest, J. B., Khatiwada, A., Mace, J. C., Alt, J. A., Bodner, T. E., Chowdhury, N. I., DiMango, E. A., Eshaghian, P. H., Getz, A. E., Gudis, D. A., Han, E. J., Hwang, P. H., Keating, C. L., Khanwalkar, A., Kimple, A. J., Lee, J. T., Li, D., Markarian, K., Norris, M., Nayak, J. V., Owens, C., Patel, Z. M., Poch, K., Schlosser, R. J., Smith, K. A., Smith, T. L., Soler, Z. M., Suh, J. D., Tervo, J. P., Turner, G. A., Wang, M. B., Saavedra, M. T., Beswick, D. M. 2023

  Abstract

  INTRODUCTION: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory-specific quality-of-life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF.METHODS: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution-based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement.RESULTS: Of 129 PwCF included, 65 had QOD scores before and 3-6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5±7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size=1.6, standard error of measurement=2.5, baseline standard deviation=4.0, and minimal detectable change=6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was -1.3±5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p<0.04).CONCLUSION: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.

  View details for DOI 10.1002/alr.23312

  View details for PubMedID 38145393

• Surgical Correction of Nasal Obstruction and Its Effect on Eustachian Tube Dysfunction Symptoms. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Daum, R., Grimm, D., Castro Silva, B. R., Huang, A. E., Lee, J. Y., Nayak, J. V., Patel, Z. M., Hwang, P. H., Chang, M. T. 2023

  Abstract

  To investigate how eustachian tube dysfunction symptoms change following surgical treatment of nonsinusitis-related nasal obstruction.Retrospective chart review.Single academic center.We assessed patients who underwent septoplasty, turbinate reduction, or both for nasal obstruction. Chronic sinusitis patients were excluded. Eustachian tube dysfunction (ETD) symptoms were studied using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), collected preoperatively and postoperatively (1 week, 1 month, 3 months, 6 months postop). Patients with preoperative ETDQ-7 > 14.5 were considered to have clinically significant symptoms. Sinonasal outcomes test scores were also assessed. Pre- and postoperative ETDQ-7 scores were compared using t test. Multivariate linear regression analysis identified factors associated with ETDQ-7 change.We analyzed 259 patients. Preoperatively, 37.5% of patients with nasal obstruction had clinically significant ETD symptoms. These patients exhibited significant improvement in ETDQ-7 at all postoperative timepoints from 23.3 ± 7.6 at baseline to 19.1 ± 9.1 at 1 week, 16.5 ± 8.0 at 1 month, 16.2 ± 7.8 at 3 months, and 16.7 ± 10.4 at 6 months (all P < .01). In patients without baseline ETD symptoms, (baseline ETDQ-7: 9.1 ± 2.3) ETDQ-7 scores did not change significantly at postoperative timepoints, except for an acute worsening at 1 week postoperatively (10.7 ± 5.1, P < .001). Regression analysis showed that higher preoperative ETDQ-7 score (β = -0.84, 95% confidence interval [CI]: -1.10 to -0.59) and postoperative antihistamine spray usage (β = -8.70, 95% CI: -14.20 to -3.20) were associated with ETDQ-7 improvement, while comorbid GERD (β = 7.50, 95% CI: 3.42-11.58) and asthma (β = 5.62, 95% CI: 0.80-10.45) were negatively associated with improvement.Surgical correction of nasal obstruction may improve ETD symptoms.

  View details for DOI 10.1002/ohn.607

  View details for PubMedID 38037398

• Factors that predict pursuing sinus surgery in the era of highly effective modulator therapy. International forum of allergy & rhinology Beswick, D. M., Han, E. J., Mace, J. C., Markarian, K., Alt, J. A., Bodner, T. E., Chowdhury, N. I., Eshaghian, P. H., Getz, A. E., Hwang, P. H., Khanwalkar, A., Kimple, A. J., Lee, J. T., Li, D. A., Norris, M., Nayak, J. V., Owens, C., Patel, Z., Poch, K., Schlosser, R. J., Smith, K. A., Smith, T. L., Soler, Z. M., Suh, J. D., Turner, G., Wang, M. B., Taylor-Cousar, J. L., Saavedra, M. 2023

  Abstract

  BACKGROUND: Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality-of-life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied.METHODS: Adult PwCF + CRS were enrolled into a prospective, observational, multi-institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS.RESULTS: Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT-22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire-9-Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire-Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p<0.050). Multivariable regression identified that worse SNOT-22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.16, p=0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004-0.34, p=0.004) was associated with pursing medical therapy.CONCLUSIONS: Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.

  View details for DOI 10.1002/alr.23270

  View details for PubMedID 37725072

• The Serpentine Sign: A Reliable Endoscopic and Radiographic Finding in Empty Nose Syndrome. The Laryngoscope Dholakia, S. S., Grimm, D., Daum, R., Bravo, D. T., Salvi, N., Zarabanda, D., Overdevest, J. B., Thamboo, A., Nakayama, T., Nayak, J. V. 2023

  Abstract

  Empty nose syndrome (ENS) is a relatively uncommon disease that greatly impacts the quality of life and presents diagnostic challenges. We sought to identify objective clinical findings unique to patients with ENS, and in doing so identified compensatory mucosal hypertrophy in an alternating, undulating swelling on endoscopy and coronal computerized tomography (CT) that we have termed the "Serpentine Sign." Here, we investigated whether this radiographic finding is a reliable manifestation in ENS patients.Retrospective review was undertaken to identify ENS patients with past turbinoplasty, an ENS6Q score of at least 11/30, and symptomatic improvement with the cotton placement test. Control patients without complaints of ENS symptoms (ENS6Q < 11) were identified for comparison. ENS and control patients had coronal CT imaging available to evaluate for the Serpentine Sign, as well as ENS6Q scores, and histologic analysis of nasal tissue.34 ENS and 74 control patients were evaluated for the presence of the Serpentine Sign. Of the 34 patients with ENS, 18 exhibited this radiographic finding on CT imaging (52.9%) compared to 0 of the 74 control patients (p < 0.0001). Further analysis demonstrated that ENS patients with the Serpentine Sign had lower median scores on ENS6Q than ENS patients without (17.5 vs. 22, p = 0.033). Histology revealed disorganized subepithelium rich in seromucinous glands similar to the nasal septum swell body.The "Serpentine Sign" is a unique presentation of hypertrophic change to the nasal septum soft tissue that is specific to ENS patients and may serve as a reliable radiographic and endoscopic finding in diagnosis.IV Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30938

  View details for PubMedID 37702458

• Eustachian tube dysfunction symptoms after endonasal skull base surgery. International forum of allergy & rhinology Grimm, D., Daum, R., Castro Silva, B. R., Lee, C. K., Fernandez-Miranda, J. C., Nayak, J. V., Patel, Z. M., Hwang, P. H., Chang, M. T. 2023

  Abstract

  ETD symptoms are present in 16% patients with underlying skull base pathology. Preoperative ETD symptoms improve following surgical treatment of skull base pathology. ETD symptoms may worsen in patients with central, posterior, or malignant skull base pathology.

  View details for DOI 10.1002/alr.23266

  View details for PubMedID 37694445

• Development of a shortwave infrared sinuscope for the detection of cerebrospinal fluid leaks. Journal of biomedical optics Klein, T. W., Yang, S., Tusty, M. A., Nayak, J. V., Chang, M. T., Bruns, O. T., Bischof, T. S., Valdez, T. A. 2023; 28 (9): 094803

  Abstract

  Cerebrospinal fluid (CSF) rhinorrhea (leakage of brain fluid from the nose) can be difficult to identify and currently requires invasive procedures, such as intrathecal fluorescein, which requires a lumbar drain placement. Fluorescein is also known to have rare but significant side effects including seizures and death. As the number of endonasal skull base cases increases, the number of CSF leaks has also increased for which an alternative diagnostic method would be highly advantageous to patients.We aim to develop an instrument to identify CSF leaks based on water absorption in the shortwave infrared (SWIR) without the need of intrathecal contrast agents. This device needed to be adapted to the anatomy of the human nasal cavity while maintaining low weight and ergonomic characteristics of current surgical instruments.Absorption spectra of CSF and artificial CSF were obtained to characterize the absorption peaks that could be targeted with SWIR light. Different illumination systems were tested and refined prior to adapting them into a portable endoscope for testing in 3D-printed models and cadavers for feasibility.We identified CSF to have an identical absorption profile as water. In our testing, a narrowband laser source at 1480 nm proved superior to using a broad 1450 nm LED. Using a SWIR enabling endoscope set up, we tested the ability to detect artificial CSF in a cadaver model.An endoscopic system based on SWIR narrowband imaging can provide an alternative in the future to invasive methods of CSF leak detection.

  View details for DOI 10.1117/1.JBO.28.9.094803

  View details for PubMedID 37188003

  View details for PubMedCentralID PMC10181794

• Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies. International forum of allergy & rhinology Fleseriu, C. M., Beswick, D. M., Maoz, S. L., Hwang, P. H., Choby, G., Kuan, E. C., Chan, E. P., Adappa, N. D., Geltzeiler, M., Getz, A. E., Humphries, I. M., Le, C. H., Abuzeid, W. M., Chang, E. H., Jafari, A., Kingdom, T. T., Kohanski, M. A., Lee, J. K., Nabavizadeh, S. A., Nayak, J. V., Palmer, J. N., Patel, Z. M., Pinheiro-Neto, C. D., Resnick, A. C., Smith, T. L., Snyderman, C. H., St John, M. A., Storm, J., Suh, J. D., Wang, M. B., Wang, E. W. 2023

  Abstract

  The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling.Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL.Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005).Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.

  View details for DOI 10.1002/alr.23261

  View details for PubMedID 37646428

• Multicenter Survival Analysis and Application of an Olfactory Neuroblastoma Staging Modification Incorporating Hyams Grade. JAMA otolaryngology-- head & neck surgery Choby, G., Geltzeiler, M., Almeida, J. P., Champagne, P. O., Chan, E., Ciporen, J., Chaskes, M. B., Fernandez-Miranda, J., Gardner, P., Hwang, P., Ji, K. S., Kalyvas, A., Kong, K. A., McMillan, R., Nayak, J., O'Byrne, J., Patel, C., Patel, Z., Peris Celda, M., Pinheiro-Neto, C., Sanusi, O., Snyderman, C., Thorp, B. D., Van Gompel, J. J., Young, S. C., Zenonos, G., Zwagerman, N. T., Wang, E. W. 2023

  Abstract

  Current olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence.The primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence.This retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers.Standard-of-care ONB treatment.The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction.A total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18).The study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.

  View details for DOI 10.1001/jamaoto.2023.1939

  View details for PubMedID 37535372

• International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System. Journal of neurological surgery. Part B, Skull base Lechner, M., Takahashi, Y., Turri-Zanoni, M., Ferrari, M., Liu, J., Counsell, N., Mattavelli, D., Rampinelli, V., Vermi, W., Lombardi, D., Saade, R., Park, K. W., Schartinger, V. H., Franchi, A., Facco, C., Sessa, F., Battocchio, S., Fenton, T. R., Vaz, F. M., O'Flynn, P., Howard, D., Stimpson, P., Wang, S., Hannan, S. A., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Dave, M., Fleming, J. C., Thomson, D., Zhu, T., Teschendorff, A., Royle, G., Steele, C., Jimenez, J. E., Laco, J., Wang, E. W., Snyderman, C., Lacy, P. D., Woods, R., O'Neill, J. P., Saraswathula, A., Kaur, R. P., Zhao, T., Ramanathan, M., Gallia, G. L., London, N. R., Le, Q. T., West, R. B., Patel, Z. M., Nayak, J. V., Hwang, P. H., Hermsen, M., Llorente, J., Facchetti, F., Nicolai, P., Bossi, P., Castelnuovo, P., Jay, A., Carnell, D., Forster, M. D., Bell, D. M., Lund, V. J., Hanna, E. Y. 2023; 84 (4): 307-319

  Abstract

  Objectives  Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods  We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results  One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p  < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p  = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p  = 0.036). Conclusions  We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

  View details for DOI 10.1055/s-0042-1750178

  View details for PubMedID 37405239

  View details for PubMedCentralID PMC10317567

• Incidence of hypocortisolism with long-term budesonide irrigations for chronic rhinosinusitis. International forum of allergy & rhinology Silva, B. R., Tyler, M. A., Ma, Y., Wang, J., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2023

  Abstract

  Budesonide irrigations (BI) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term budesonide irrigation with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up.Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥ 6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012-22. We correlated cortisol levels with use of BI and other forms of corticosteroids.We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40-50%. Lower cortisol levels were associated with male gender (p<.0001) and concomitant use of oral and inhaled steroids (p<.0001). Duration of budesonide irrigation use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289).Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids, and male gender may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use budesonide irrigations regularly, particularly in patients using other forms of corticosteroids with known systemic absorption. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.23227

  View details for PubMedID 37389470

• Long-term quality of life after treatment in sinonasal malignancy: A prospective, multi-center study. International forum of allergy & rhinology Maoz, S. L., Wang, E. W., Hwang, P. H., Choby, G., Kuan, E. C., Fleseriu, C. M., Chan, E. P., Adappa, N. D., Geltzeiler, M., Getz, A. E., Humphreys, I. M., Le, C. H., Abuzeid, W. M., Chang, E. H., Jafari, A., Kingdom, T. T., Kohanski, M. A., Lee, J. K., Lazor, J. W., Nabavizadeh, A., Nayak, J. V., Palmer, J. N., Patel, Z. M., Pinheiro-Neto, C. D., Resnick, A. C., Smith, T. L., Snyderman, C. H., St John, M. A., Storm, P. B., Suh, J. D., Wang, M. B., Sim, M. S., Beswick, D. M. 2023

  Abstract

  Quality-of-life (QOL) for individuals with sinonasal malignancy (SNM) is significantly understudied yet critical for counseling and may impact treatment. This study evaluated the how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year post-treatment timeframe.Patients with SNM who underwent definitive treatment with curative intent were enrolled into a prospective, multi-site, longitudinal observational study. QOL was assessed using the Sinonasal Outcome Test-22 (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pre-treatment baseline and multiple follow-ups through 5 years post-treatment. Multivariable modelling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL.194 patients with SNM were analyzed. All QOL indices were impaired at pre-treatment baseline and improved post-treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6-9 months post-treatment. Patients who underwent open compared to endoscopic tumor resection had worse generalized QOL (p<0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p<0.001; UWQOL-Physical, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01).Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves following treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL post-treatment. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.23171

  View details for PubMedID 37082883

• The Utility of a "Second-Look" Debridement Following Endonasal Skull Base Surgery in the Pediatric Population JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Chang, M. T., Huang, A. E., Quon, J. L., Fernandez-Miranda, J. C., Wen, C. Z., Eide, J. G., Kshirsagar, R. S., Qian, Z., Nayak, J. V., Hwang, P. H., Adappa, N. D., Patel, Z. M. 2023

  View details for DOI 10.1055/a-2048-7564

  View details for Web of Science ID 000960953100002

• International consensus statement on allergy and rhinology: Allergic rhinitis - 2023. International forum of allergy & rhinology Wise, S. K., Damask, C., Roland, L. T., Ebert, C., Levy, J. M., Lin, S., Luong, A., Rodriguez, K., Sedaghat, A. R., Toskala, E., Villwock, J., Abdullah, B., Akdis, C., Alt, J. A., Ansotegui, I. J., Azar, A., Baroody, F., Benninger, M. S., Bernstein, J., Brook, C., Campbell, R., Casale, T., Chaaban, M., Chew, F. T., Chambliss, J., Cianferoni, A., Custovic, A., Davis, E. M., DelGaudio, J. M., Ellis, A. K., Flanagan, C., Fokkens, W. J., Franzese, C., Greenhawt, M., Gill, A., Halderman, A., Hohlfeld, J. M., Incorvaia, C., Joe, S. A., Joshi, S., Kuruvilla, M. E., Kim, J., Klein, A. M., Krouse, H. J., Kuan, E. C., Lang, D., Larenas-Linnemann, D., Laury, A. M., Lechner, M., Lee, S. E., Lee, V. S., Loftus, P., Marcus, S., Marzouk, H., Mattos, J., McCoul, E., Melen, E., Mims, J. W., Mullol, J., Nayak, J. V., Oppenheimer, J., Orlandi, R. R., Phillips, K., Platt, M., Ramanathan, M., Raymond, M., Rhee, C. S., Reitsma, S., Ryan, M., Sastre, J., Schlosser, R. J., Schuman, T. A., Shaker, M. S., Sheikh, A., Smith, K. A., Soyka, M. B., Takashima, M., Tang, M., Tantilipikorn, P., Taw, M. B., Tversky, J., Tyler, M. A., Veling, M. C., Wallace, D., Wang, D. Y., White, A., Zhang, L. 2023

  Abstract

  In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work.ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost.The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

  View details for DOI 10.1002/alr.23090

  View details for PubMedID 36878860

• Radiographic predictors of occult intracranial involvement in olfactory neuroblastoma patients. International forum of allergy & rhinology Geltzeiler, M., Choby, G. W., Ji, K. S., Mace, J. C., Almeida, J. P., de Almeida, J., Champagne, P., Chan, E., Ciporen, J. N., Chaskes, M. B., Cornell, S., Drozdowski, V., Fernandez-Miranda, J., Gardner, P. A., Hwang, P. H., Kalyvas, A., Kong, K. A., McMillan, R. A., Nayak, J. V., Patel, C., Patel, Z. M., Celda, M. P., Pinheiro-Neto, C., Sanusi, O. R., Snyderman, C. H., Thorp, B. D., Van Gompel, J. J., Zadeh, G., Zenonos, G., Zwagerman, N. T., Wang, E. W. 2023

  Abstract

  BACKGROUND: Traditional management of olfactory neuroblastoma (ONB) includes margin negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be over-treating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes.METHODS: This retrospective, multi-institutional cohort study examined clinical covariates associated with occult intracranial involvement. Patient demographics, staging, Hyam's grade and pathologic involvement of dura, olfactory bulb/tract and brain were collected. Diagnostic imaging was reviewed. Positive and negative predictive value (NPV) were estimated along with effect size estimates. Cox hazard regression examined associations with overall (OS) and disease-free survival (DFS).RESULTS: 224 subjects with new diagnoses of ONB (2005-2021) were identified. Skull base bone involvement on computed tomography (CT) had the highest NPV for pathologic dura (88.0%), olfactory bulb (88%), and brain involvement (97.3%). Hyam's grade category was significantly associated with dural involvement (phiC = 0.26; 95% CI: 0.16, 0.42). Subjects without radiologic skull base involvement (n = 66) had pathologic positivity of 12.1%. Within this subgroup, Hyam's grade was clinically significant for dural positivity (phi = 0.34; 95% CI: -0.12, 0.71) with 28.6% involvement in high grade tumors. Neither clinical nor pathologic positivity of intracranial structures were associated with significantly different OS or DFS.CONCLUSIONS: Both CT and MRI had reasonably good NPV for involvement of dura and olfactory bulb. Higher Hyam's grade was associated with dural involvement. Patients with low-grade tumors not involving the skull base may be suitable for avoiding skull base resection, however further investigation is warranted. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.23145

  View details for PubMedID 36841933

• Tranexamic acid does not significantly lower postoperative bleeding after endoscopic sinus and nasal surgery. International forum of allergy & rhinology Khanwalkar, A., Chan, E., Roozdar, P., Kim, D., Ma, Y., Hwang, P. H., Nayak, J. V., Patel, Z. M. 2023

  Abstract

  BACKGROUND: Postoperative epistaxis is a known possibility following endoscopic sinonasal surgery. Tranexamic acid (TXA) has been shown to reduce intraoperative blood loss and improve the visual field. This study evaluates the clinical efficacy of TXA when given at end of surgery to reduce postoperative bleeding.METHODS: This randomized, double-blinded placebo-controlled trial was conducted from April to November 2021. Patients scheduled to undergo endoscopic sinus or nasal surgery were randomized to receive an intravenous dose of 1g TXA or saline intraoperatively prior to extubation. A 10-inch visual analog scale (VAS) was used to query patients regarding postoperative bleeding each day for one week. The medical record was examined to determine the need for additional evaluations or interventions for epistaxis.RESULTS: 40 patients completed the study. The mean/SD postoperative bleeding VAS for the TXA group on the day of surgery was not significantly different from the saline group (4.82 [2.18] in vs 5.03 [2.14] in, p = 0.8). There were no significant differences between treatment arms on any postoperative day through day 7 (0.67 [1.84] in vs 0.87 [0.99] in, p = 0.7), nor in the reduction in VAS compared to the respective baseline on the day of surgery. There were no significant differences in terms of additional interventions (e.g. additional evaluation in recovery, ED, or clinic, need for packing, or return to OR).CONCLUSION: While TXA has previously demonstrated efficacy to reduce intraoperative bleeding during sinonasal surgery, when postoperative bleeding is already minimal at baseline, TXA does not appear to reduce it significantly further. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.23127

  View details for PubMedID 36608352

• Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2. Nature microbiology Yang, J., Xiao, Y., Lidsky, P. V., Wu, C., Bonser, L. R., Peng, S., Garcia-Knight, M. A., Tassetto, M., Chung, C., Li, X., Nakayama, T., Lee, I. T., Nayak, J. V., Ghias, K., Hargett, K. L., Shoichet, B. K., Erle, D. J., Jackson, P. K., Andino, R., Shu, X. 2023; 8 (1): 121-134

  Abstract

  The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright fluorescence signal that requires no exogenous cofactors. Utilizing this reporter, we carried out a high-throughput screening of small-molecule libraries. We identified three natural compounds that block replication of SARS-CoV-2 in both Vero cells and human primary nasal and bronchial epithelial cells. Cell biological and biochemical experiments validated all three compounds and showed that they block the early stages of viral infection. Two of the inhibitors, bruceineA and gamabufotalin, were also found to block replication of the Delta and Omicron variants of SARS-CoV-2. Both bruceineA and gamabufotalin exhibited potent antiviral activity in K18-hACE2 and wild-type C57BL6/J mice, as evidenced by reduced viral titres in the lung and brain, and protection from alveolar and peribronchial inflammation in the lung, thereby limiting disease progression. We propose that our fluorescent assay can be applied to identify antiviral compounds with potential as therapeutic treatment for COVID-19 and other respiratory diseases.

  View details for DOI 10.1038/s41564-022-01288-5

  View details for PubMedID 36604514

• SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming. Cell Wu, C., Lidsky, P. V., Xiao, Y., Cheng, R., Lee, I. T., Nakayama, T., Jiang, S., He, W., Demeter, J., Knight, M. G., Turn, R. E., Rojas-Hernandez, L. S., Ye, C., Chiem, K., Shon, J., Martinez-Sobrido, L., Bertozzi, C. R., Nolan, G. P., Nayak, J. V., Milla, C., Andino, R., Jackson, P. K. 2022

  Abstract

  How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid cultures, we found that the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24h post-infection and trigger formation of apically extended and highly branched microvilli that organize viral egress from the microvilli back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Phosphoproteomics and kinase inhibition reveal that microvillar remodeling is regulated by p21-activated kinases (PAK). Importantly, Omicron variants bind with higher affinity to motile cilia and show accelerated viral entry. Our work suggests that motile cilia, microvilli, and mucociliary-dependent mucus flow are critical for efficient virus replication in nasal epithelia.

  View details for DOI 10.1016/j.cell.2022.11.030

  View details for PubMedID 36580912

• High prevalence of persistent smell loss and qualitative smell dysfunction during the COVID-19 pandemic in the United States: urgent need for clinical trials. International forum of allergy & rhinology Lechner, M., Liu, J., Counsell, N., Yan, C. H., Paun, S., Eynon-Lewis, N., Sutton, L., Jayaraj, S., Batterham, R. L., Hopkins, C., Philpott, C., Lund, V. J., Hatter, M., Abdelwahab, M., Holsinger, F. C., Capasso, R., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2022

  View details for DOI 10.1002/alr.23100

  View details for PubMedID 36409559

• Effect of dupilumab on Eustachian tube dysfunction in patients with chronic rhinosinusitis with nasal polyposis. International forum of allergy & rhinology Chang, M., Roozdar, P., Lin, Y. T., Lee, J. Y., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2022

  View details for DOI 10.1002/alr.23110

  View details for PubMedID 36399364

• International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Lechner, M., Takahashi, Y., Turri-Zanoni, M., Ferrari, M., Liu, J., Counsell, N., Mattavelli, D., Rampinelli, V., Vermi, W., Lombardi, D., Saade, R., Park, K., Schartinger, V. H., Franchi, A., Facco, C., Sessa, F., Battocchio, S., Fenton, T. R., Vaz, F. M., O'Flynn, P., Howard, D., Stimpson, P., Wang, S., Hannan, S., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Dave, M., Fleming, J. C., Thomson, D., Zhu, T., Teschendorff, A., Royle, G., Steele, C., Jimenez, J. E., Laco, J., Wang, E. W., Snyderman, C., Lacy, P. D., Woods, R., O'Neill, J. P., Saraswathula, A., Kaur, R., Zhao, T., Ramanathan, M., Gallia, G. L., London, N. R., Le, Q., West, R. B., Patel, Z. M., Nayak, J. V., Hwang, P. H., Hermsen, M., Llorente, J., Facchetti, F., Nicolai, P., Bossi, P., Castelnuovo, P., Jay, A., Carnell, D., Forster, M. D., Bell, D. M., Lund, V. J., Hanna, E. Y. 2022

  View details for DOI 10.1055/s-0042-1750178

  View details for Web of Science ID 000822748800001

• Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes. Scientific reports Mohyeldin, A., Katznelson, L. J., Hoffman, A. R., Asmaro, K., Ahmadian, S. S., Eltobgy, M. M., Nayak, J. V., Patel, Z. M., Hwang, P. H., Fernandez-Miranda, J. C. 2022; 12 (1): 9919

  Abstract

  Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3-30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.

  View details for DOI 10.1038/s41598-022-12980-1

  View details for PubMedID 35705579

• Endoscopic Endonasal Approach for Suprasellar Mature Teratoma in Growing Teratoma Syndrome: 2-Dimensional Operative Video. Operative neurosurgery (Hagerstown, Md.) Vigo, V., Prolo, L. M., Nunez, M. A., Nayak, J. V., Fernandez-Miranda, J. C. 2022

  Abstract

  Intracranial growing teratoma syndrome is a rare phenomenon characterized by enlargement of a germ cell tumor during or after adjuvant therapy despite normalization of tumor markers.1,2 It has been suggested that chemotherapy acts on the nonteratomatous components or induces differentiation of the immature germ cells to mature teratomatous phenotype.3 An 8-year-old boy presented with headache, emesis, and blurry vision. Neuroimaging revealed hydrocephalus with multiple central nervous system masses: pineal gland, suprasellar region, and spine (T8). Elevated serum and cerebrospinal fluid levels of alpha-fetoprotein and beta-human chorionic gonadotropin were found. A ventriculoperitoneal shunt was placed. Despite chemotherapy and decreasing tumor markers, the pineal mass rapidly enlarged, and the patient became somnolent. He underwent microsurgical resection with the diagnosis of mixed germ cell tumor. During his second chemotherapy cycle, the patient endorsed worsening vision and panhypopituitarism. Imaging demonstrated enlargement and honeycomb appearance of the suprasellar mass. The patient and family consented to the procedure, and an endoscopic endonasal approach was performed to access the retroinfundibular region. Removal of the nonfunctional pituitary gland and dorsum sellae was performed. Careful dissection of the tumor from the optic apparatus, hypothalamus, and perforating arteries allowed total resection. Reconstruction with fascia lata and nasoseptal flap was performed. Mature teratoma was found histologically. Postoperative course was complicated by flap hemorrhage resolved by surgical revision. Postoperative imaging showed complete resection. The patient was discharged without other complications and was making excellent recovery. To the best of our knowledge, this is the first reported case of hypothalamic intracranial growing teratoma syndrome successfully treated using an endoscopic endonasal approach.

  View details for DOI 10.1227/ons.0000000000000166

  View details for PubMedID 35383719

• In Response to Inferior Meatus Augmentation Procedure (IMAP) for Treatment of Empty Nose Syndrome. The Laryngoscope Chang, M. T., Nayak, J. V. 2022

  View details for DOI 10.1002/lary.30119

  View details for PubMedID 35366011

• Transplantation of Gene Edited Upper Airway Basal Stem Cells in Immunocompromised Mice Using Fibrinogen Based Scaffolds Vaidyanathan, S., Bravo, D. T., Desai, T. J., Porteus, M. H., Nayak, J. V. CELL PRESS. 2022: 407

  View details for Web of Science ID 000794043702043

• Inferior Meatus Augmentation Procedure (IMAP) for Treatment of Empty Nose Syndrome. The Laryngoscope Chang, M. T., Bartho, M., Kim, D., Tsai, E. F., Yang, A., Dholakia, S. S., Khanwalkar, A., Rao, V. K., Thamboo, A., Lechner, M., Nayak, J. V. 1800

  View details for DOI 10.1002/lary.30001

  View details for PubMedID 35072280

• Deep learning classification of inverted papilloma malignant transformation using 3D convolutional neural networks and magnetic resonance imaging. International forum of allergy & rhinology Liu, G. S., Yang, A., Kim, D., Hojel, A., Voevodsky, D., Wang, J., Tong, C. C., Ungerer, H., Palmer, J. N., Kohanski, M. A., Nayak, J. V., Hwang, P. H., Adappa, N. D., Patel, Z. M. 2022

  Abstract

  Distinguishing benign inverted papilloma (IP) tumors from those that have undergone malignant transformation to squamous cell carcinoma (IP-SCC) is important but challenging to do preoperatively. Magnetic resonance imaging (MRI) can help differentiate these two entities, however no established method exists that can automatically synthesize all potentially relevant MRI image features to distinguish IP and IP-SCC. We explored a deep learning approach, using 3-dimensional convolutional neural networks (CNNs), to address this challenge.Retrospective chart reviews were performed at two institutions to create a dataset of preoperative MRIs with corresponding surgical pathology reports. The MRI dataset included all available MRI sequences in the axial plane, which were used to train, validate, and test three CNN models. Saliency maps were generated to visualize areas of MRIs with greatest influence on predictions.A total of 90 patients with IP (n = 64) or IP-SCC (n = 26) tumors were identified, with a total of 446 images of distinct MRI sequences for IP (n = 329) or IP-SCC (n = 117). The best CNN model, All-Net, demonstrated a sensitivity of 66.7%, specificity of 81.5%, overall accuracy of 77.9%, and ROC-AUC of 0.80 ([0.682 - 0.898], 95% confidence interval) for test classification performance. The other two models, Small-All-Net and Elastic-All-Net, showed similar performances.A deep learning approach with 3-dimensional CNNs can distinguish IP and IP-SCC with moderate test classification performance. Although CNNs demonstrate promise to enhance the prediction of IP-SCC using MRIs, more data is needed before they can reach the predictive value already established by human MRI evaluation. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.22958

  View details for PubMedID 34989484

• Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma. European journal of cancer (Oxford, England : 1990) Lechner, M., Takahashi, Y., Turri-Zanoni, M., Liu, J., Counsell, N., Hermsen, M., Kaur, R. P., Zhao, T., Ramanathan, M. J., Schartinger, V. H., Emanuel, O., Helman, S., Varghese, J., Dudas, J., Riechelmann, H., Sprung, S., Haybaeck, J., Howard, D., Engel, N. W., Stewart, S., Brooks, L., Pickles, J. C., Jacques, T. S., Fenton, T. R., Williams, L., Vaz, F. M., O'Flynn, P., Stimpson, P., Wang, S., Hannan, S. A., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Royle, G., Franchi, A., Maragliano, R., Battocchio, S., Bewicke-Copley, H., Pipinikas, C., Webster, A., Thirlwell, C., Ho, D., Teschendorff, A., Zhu, T., Steele, C. D., Pillay, N., Vanhaesebroeck, B., Mohyeldin, A., Fernandez-Miranda, J., Park, K. W., Le, Q., West, R. B., Saade, R., Manes, R. P., Omay, S. B., Vining, E. M., Judson, B. L., Yarbrough, W. G., Sansovini, M., Silvia, N., Grassi, I., Bongiovanni, A., Capper, D., Schuller, U., Thavaraj, S., Sandison, A., Surda, P., Hopkins, C., Ferrari, M., Mattavelli, D., Rampinelli, V., Facchetti, F., Nicolai, P., Bossi, P., Henriquez, O. A., Magliocca, K., Solares, C. A., Wise, S. K., Llorente, J. L., Patel, Z. M., Nayak, J. V., Hwang, P. H., Lacy, P. D., Woods, R., O'Neill, J. P., Jay, A., Carnell, D., Forster, M. D., Ishii, M., London, N. R., Bell, D. M., Gallia, G. L., Castelnuovo, P., Severi, S., Lund, V. J., Hanna, E. Y. 1800

  Abstract

  INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n=278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

  View details for DOI 10.1016/j.ejca.2021.09.046

  View details for PubMedID 34980502

• Venous thromboembolism rates and risk factors following endoscopic skull base surgery. International forum of allergy & rhinology Chang, M. T., Jitaroon, K., Song, S., Roozdar, P., Wangworat, Y., Ibrahim, N., Ma, Y., Rao, V. K., Chang, S. D., Fernandez-Miranda, J. C., Patel, Z. M., Dodd, R. L., Hwang, P. H., Harsh, G. R., Nayak, J. V. 2021

  Abstract

  BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. The objective of this study was to assess the rate and risk factors for VTE in endoscopic skull base surgery (ESBS).METHODS: This was a retrospective review of adults undergoing ESBS at a tertiary academic center. Incidence of VTE in the 30-day postoperative period was recorded. Logistic regression analyses identified factors associated with VTE.RESULTS: 1122 ESBS cases between 2009 and 2019 were studied. Almost no cases (96.1%) employed perioperative VTE chemoprophylaxis. The overall incidence of VTE was 2.3% (26/1122). Malignant pathologies had a higher rate of VTE compared to nonmalignant pathologies (4.5% vs 2.0%, OR 2.85, 95%CI 1.22-6.66). Factors associated with an increased risk of VTE included a Caprini score greater than 5 (OR 1.53, 95% CI 1.28-1.83); multiple preoperative endocrinopathies such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (OR 22.48, 95% CI 3.93-128.70), adrenal insufficiency (OR 5.24, 95% CI 1.82-15.03), hypercortisolism (OR 4.46, 95% CI 1.47-13.56), and hypothyroidism (OR 3.69, 95% CI 1.66-8.20), each 10-hour increment of lumbar drain duration (OR 1.16, 95%CI 1.08-1.25), and each 10-hour increment for duration of hospitalization (OR 1.05, 95% CI 1.03-1.06).CONCLUSIONS: The incidence of VTE following ESBS is relatively low. Factors with a higher association with VTE include malignancy, preoperative endocrinopathies, higher Caprini score, prolonged lumbar drain duration, and prolonged hospitalization. Further study is needed to validate these findings and to refine clinical decision making around perioperative VTE prophylaxis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.22943

  View details for PubMedID 34894093

• Comparison of endoscopic sinus surgery timing in lung transplant patients with cystic fibrosis. International forum of allergy & rhinology Johnson, J. R., Hwang, P. H., Nayak, J. V., Patel, Z. M. 2021

  Abstract

  BACKGROUND: No studies have investigated when endoscopic sinus surgery (ESS) is best performed in lung transplant patients with cystic fibrosis (CF). We sought to examine the effects of ESS timing on pulmonary health in this population.METHODS: A retrospective review of all adult lung transplant patients with CF who underwent ESS at our academic medical center over a near 25-year period was performed. Patients were split into two groups based on median time from lung transplantation to ESS. Twenty-three patients were included (12 ESS early and 11 ESS delayed). Outcomes included changes in pulmonary function tests (PFTs) from baseline, pre-operative to post-operative measurements, the number and duration of hospitalizations for pulmonary exacerbations, and the number of antibiotic courses used specifically to treat pulmonary exacerbations during the 12 months before and after ESS.RESULTS: Baseline demographics, operative history, and pulmonary function characteristics were similar between groups. While the ESS early group saw significant improvement from pre-operative percent predicted FEV1 (ppFEV1 ) at 12 months post-operatively (CI: 0.729 - 11.452, P=0.030), there were no significant post-operative PFT changes for the ESS delayed group. Post-operative improvement in FEV1 and ppFEV1 at 12 months was significantly higher for the ESS early group relative to the ESS delayed group (CI: 0.010 - 0.583, P=0.043; CI: 1.240 - 16.692, P=0.025; respectively). The ESS early group had a significant reduction in the need for total antibiotic courses compared to the ESS delayed group (ESS early median: -1, IQR: -1.5 to -0.5vs ESS delayed median: 0, IQR: 0 to 0; P=0.027).CONCLUSION: Earlier ESS interventions following lung transplantation may improve pulmonary function and attenuate pulmonary exacerbations in CF patients. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/alr.22935

  View details for PubMedID 34875144

• Inflammatory molecular endotypes of nasal polyps derived from Caucasian and Japanese populations. The Journal of allergy and clinical immunology Nakayama, T., Lee, I. T., Le, W., Tsunemi, Y., Borchard, N. A., Zarabanda, D., Dholakia, S. S., Gall, P. A., Yang, A., Kim, D., Akutsu, M., Kashiwagi, T., Patel, Z. M., Hwang, P. H., Frank, D. N., Haruna, S., Ramakrishnan, V. R., Nolan, G. P., Jiang, S., Nayak, J. V. 2021

  Abstract

  BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Little is known currently about possible distinguishing factors underlying these inflammatory differences.OBJECTIVE: To interrogate for differences between Caucasian and Japanese CRSwNP disease using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs).METHODS: We performed whole transcriptome RNA sequencing (RNA-seq) with endotype stratification of NPs from 8 Caucasian (residing in USA) and 9 Japanese (residing in Japan) patients. Reproducibility was confirmed by qPCR in an independent validation set of 46 Caucasian and 31 Japanese patients. Single-cell RNA-seq stratified key cell types for contributory transcriptional signatures.RESULTS: Unsupervised clustering analysis identified two major endotypes present within both NP cohorts, which have previously been reported at the cytokine level: 1) type 2 endotype and 2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct NP subgroups (p = 0.03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells.CONCLUSION: NPs from both racial groups harbor the same two major endotypes, which we determine are present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

  View details for DOI 10.1016/j.jaci.2021.11.017

  View details for PubMedID 34863854

• The Effect of Povidone-Iodine Nasal Spray on COVID-19 Nasopharyngeal Viral Load in Patients: A Randomized Control Trial. The Laryngoscope Zarabanda, D., Vukkadala, N., Phillips, K. M., Qian, Z. J., Mfuh, K. O., Hatter, M., Lee, I. T., Rao, V. K., Hwang, P. H., Domb, G., Patel, Z. M., Pinsky, B. A., Nayak, J. V. 2021

  Abstract

  OBJECTIVES: To determine the effect of povidone-iodine (PVP-I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold on quantitative polymerase chain reaction (qPCR) of SARS-CoV-2 in outpatients.STUDY DESIGN: Three arm, triple blinded, randomized, placebo-controlled clinical trial.METHODS: Participants were randomized within 5days of testing positive for COVID-19 to receive nasal sprays containing either placebo (0.9% saline), 0.5% PVP-I, or 2.0% PVP-I. NP swabs for qPCR analysis were taken at baseline, 1-hour post-PVP-I spray (2 sprays/nostril), and 3days post-PVP-I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.RESULTS: Mean cycle threshold (Ct) values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP-I groups. 2.0% PVP-I group showed statistically significant improvement in all symptom categories, however also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30days of study enrollment.CONCLUSION: Saline and low concentration PVP-I nasal sprays are well tolerated. Similar reductions in SARS-CoV-2 nasopharyngeal viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30days. These data suggest that dilute versions of PVP-I nasal spray are safe for topical use in the nasal cavity, but that PVP-I does not demonstrate virucidal activity in COVID-19 positive outpatients. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/lary.29935

  View details for PubMedID 34724213

• Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers. Cell reports. Medicine Nakayama, T., Lee, I. T., Jiang, S., Matter, M. S., Yan, C. H., Overdevest, J. B., Wu, C., Goltsev, Y., Shih, L., Liao, C., Zhu, B., Bai, Y., Lidsky, P., Xiao, Y., Zarabanda, D., Yang, A., Easwaran, M., Schurch, C. M., Chu, P., Chen, H., Stalder, A. K., McIlwain, D. R., Borchard, N. A., Gall, P. A., Dholakia, S. S., Le, W., Xu, L., Tai, C., Yeh, T., Erickson-Direnzo, E., Duran, J. M., Mertz, K. D., Hwang, P. H., Haslbauer, J. D., Jackson, P. K., Menter, T., Andino, R., Canoll, P. D., DeConde, A. S., Patel, Z. M., Tzankov, A., Nolan, G. P., Nayak, J. V. 2021: 100421

  Abstract

  Understanding viral tropism is an essential step towards reducing SARS-CoV-2 transmission, decreasing mortality from COVID-19, and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head & neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in the expression of ACE2 and TMPRSS2, essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head & neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in IFN-beta1 levels between smokers and non-smokers.

  View details for DOI 10.1016/j.xcrm.2021.100421

  View details for PubMedID 34604819

• The Inferior Turbinate: Role in Normal Respiration and Airway Obstruction CURRENT OTORHINOLARYNGOLOGY REPORTS Thamboo, A., Ayoub, N., Maul, X., Nayak, J. 2021

  View details for DOI 10.1007/s40136-021-00370-6

  View details for Web of Science ID 000700971600001

• Ethacridine inhibits SARS-CoV-2 by inactivating viral particles. PLoS pathogens Li, X., Lidsky, P., Xiao, Y., Wu, C., Garcia-Knight, M., Yang, J., Nakayama, T., Nayak, J. V., Jackson, P. K., Andino, R., Shu, X. 2021; 17 (9): e1009898

  Abstract

  The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC50 ~ 0.08 muM). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescence assay. Plaque assays, RT-PCR and immunofluorescence imaging at various stages of viral infection demonstrate that the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Consistently, ethacridine is effective in various cell types, including primary human nasal epithelial cells that are cultured in an air-liquid interface. Taken together, our work identifies a promising, potent, and new use of the old drug via a distinct mode of action for inhibiting SARS-CoV-2.

  View details for DOI 10.1371/journal.ppat.1009898

  View details for PubMedID 34478458

• Assessment of Opioid Use and Analgesic Requirements After Endoscopic Sinus Surgery: A Randomized Clinical Trial. JAMA otolaryngology-- head & neck surgery Ayoub, N. F., Choby, G., Turner, J. H., Abuzeid, W. M., Raviv, J. R., Thamboo, A., Ma, Y., Chandra, R. K., Chowdhury, N. I., Stokken, J. K., O'Brien, E. K., Shah, S., Akbar, N., Roozdar, P., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2021

  Abstract

  Importance: The opioid epidemic has generated interest in optimizing opioid prescribing after common surgeries. Recent studies have shown a broad range of analgesic prescription patterns following endoscopic sinus surgery (ESS).Objective: To compare the efficacy of different analgesic regimens after ESS.Design, Setting, and Participants: This multi-institutional, nonblinded randomized clinical trial was conducted at 6 tertiary centers across the US and Canada and included participants who underwent ESS for acute or chronic rhinosinusitis. The study was conducted from March 2019 to March 2020, and the data were analyzed in November to December 2020.Interventions: All participants received acetaminophen, 650 mg, as the first-line analgesic. From there, patients were randomized to either oxycodone rescue (oxycodone, 5 mg, as second-line therapy) or ibuprofen rescue (ibuprofen, 600 mg, as second-line therapy, with oxycodone, 5 mg, reserved for breakthrough pain).Main Outcomes and Measures: Baseline characteristics and disease severity were collected at enrollment. Medication logs, pain scores, and epistaxis measures were collected until postoperative day 7. The primary outcome was the postoperative visual analog scale score for pain. Brief Pain Inventory Pain Severity and Pain Interference Scores were also collected.Results: A total of 118 patients were randomized (62 [52.5%] oxycodone rescue, 56 [47.5%] ibuprofen rescue; mean [SD] age, 46.7 [16.3] years; 44 women [44.0%]; 83 White [83.0%], 7 Black [7.0%], and 7 Asian individuals [7.0%]). After exclusions for loss to follow-up and noncompliance, 51 remained in the oxycodone rescue group and 49 in the ibuprofen rescue group. The groups had similar demographic characteristics and disease severity. Thirty-two (63%) in the oxycodone rescue group had adequate pain management with acetaminophen only, while 19 (37%) consumed at least 1 oxycodone dose. In the ibuprofen rescue group, 18 (16%) required only acetaminophen, 28 (57%) used only acetaminophen and ibuprofen, and the remaining 13 (26%) consumed 1 or more oxycodone doses. The groups had similar average acetaminophen (9.69 vs 7.96 doses; difference, 1.73; 95% CI, -1.37 to 4.83) and oxycodone (1.89 vs 0.77 doses; difference, 1.13; 95% CI, -0.11 to 2.36) use. Both groups had similar postoperative visual analog scale scores. A subanalysis that compared opioids users with nonusers showed clinically significant lower pain scores in nonusers at multiple postoperative points.Conclusions and Relevance: In this randomized clinical trial, most patients who underwent ESS could be treated postoperatively using a nonopioid regimen of either acetaminophen alone or acetaminophen and ibuprofen. Ibuprofen as a second-line therapy did not reduce overall narcotic consumption, but the overall narcotic use was low in both groups.Trial Registration: ClinicalTrials.gov Identifier: NCT03783702.

  View details for DOI 10.1001/jamaoto.2021.1839

  View details for PubMedID 34351376

• Surgical approach is associated with complication rate in sinonasal malignancy: A multicenter study. International forum of allergy & rhinology Beswick, D. M., Hwang, P. H., Adappa, N. D., Le, C. H., Humphreys DO, I. M., Getz, A. E., Suh, J. D., Aasen, D. M., Abuzeid, W. M., Chang, E. H., Kaizer, A. M., Kindgom, T. T., Kohanski, M. A., Nabavizadeh, S. A., Nayak, J. V., Palmer, J. N., Patel, Z. M., Ramakrishnan, V. R., Snyderman, C. H., St John, M. A., Wild, J., Wang, E. W. 2021

  Abstract

  BACKGROUND: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment-related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated.METHODS: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi-institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling.RESULTS: Overall, 142 patients met the inclusion criteria. Twenty-three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T-stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06-11.19).CONCLUSIONS: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings.

  View details for DOI 10.1002/alr.22833

  View details for PubMedID 34176231

• SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Cell metabolism Wu, C., Lidsky, P. V., Xiao, Y., Lee, I. T., Cheng, R., Nakayama, T., Jiang, S., Demeter, J., Bevacqua, R. J., Chang, C. A., Whitener, R. L., Stalder, A. K., Zhu, B., Chen, H., Goltsev, Y., Tzankov, A., Nayak, J. V., Nolan, G. P., Matter, M. S., Andino, R., Jackson, P. K. 2021

  Abstract

  Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic beta cells can be infected by SARS-CoV-2 and cause beta cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in beta cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic beta cells in patients who succumbed to COVID-19 and selectively infects human islet beta cells invitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces beta cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic beta cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce beta cell killing.

  View details for DOI 10.1016/j.cmet.2021.05.013

  View details for PubMedID 34081912

• Long-Term Outcomes of Inferior Meatus Augmentation Procedure to Treat Empty Nose Syndrome. The Laryngoscope Dholakia, S. S., Yang, A., Kim, D., Borchard, N. A., Chang, M. T., Khanwalkar, A., Lechner, M., Nayak, J. V. 2021

  Abstract

  OBJECTIVES/HYPOTHESIS: We sought to report the long-term, symptom-focused, prospective outcomes in empty nose syndrome (ENS) patients after undergoing inferior meatus augmentation procedure (IMAP) through use of four validated questionnaires: Empty Nose Syndrome 6-Item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9).STUDY DESIGN: Prospective case series.METHODS: A single-center prospective case series was performed for patients diagnosed with ENS who underwent IMAP between July 2017 and February 2020. Diagnosis of ENS was based on the following criteria: 1) reported discomfort with nasal breathing and/or paradoxical nasal obstruction after inferior turbinate reduction, 2) a positive ENS6Q score of at least 11, and 3) a positive cotton test. Questionnaire responses were recorded prior to surgery as well as 1, 3, 6, and 12months postoperatively.RESULTS: Seventeen eligible patients were included. Mean ENS6Q scores were significantly reduced at all postoperative time points (p<.0001, p<.0001, p<.0001, p=.0003). Of the six ENS6Q subdomains, five (suffocation, dryness, sense of diminished airflow, nasal crusting, and nasal burning) were significantly reduced 1-year postoperatively (p<.0001, p=.0004, p=.0136, p=.0114, p=.0080, respectively). SNOT-22 scores were significantly reduced at all time points (p=.0021, p=.0227, p=.0004, and p=.0025). Of the SNOT-22 subdomains, the sleep subdomain was significantly reduced 1-year postoperatively (p=.0432). Low baseline GAD-7 and PHQ-9 scores were recorded at 7 and 9.4, respectively, and although scores at all postoperative time points were reduced, there was no statistical significance.CONCLUSION: IMAP via implant of cadaveric rib cartilage provides significant, long-term improvements in ENS-specific and general sinonasal symptoms.LEVEL OF EVIDENCE: IV Laryngoscope, 2021.

  View details for DOI 10.1002/lary.29593

  View details for PubMedID 33991117

• Evaluating the Use of Fibrinogen Based Scaffolds to Transplant Airway Basal Stem Cells for the Treatment of Cystic Fibrosis Vaidyanathan, S., Bravo, D. T., Nayak, J. V., Porteus, M. H. CELL PRESS. 2021: 260-261

  View details for Web of Science ID 000645188700526

• SARS-CoV-2 entry factors are expressed in nasal, ocular, and oral tissues: implications for COVID-19 prophylaxes/therapeutics Lee, I., Nakayama, T., Jiang, S., Goltsev, Y., Schurch, C., Zhu, B., McIlwain, D., Chu, P., Chen, H., Tzankov, A., Matter, M., Nayak, J., Nolan, G. MOSBY-ELSEVIER. 2021: AB2

  View details for Web of Science ID 000629158000005

• The empty nose syndrome 6-item questionnaire (ENS6Q): a diagnostic tool to distinguish empty nose syndrome from primary nasal obstruction. International forum of allergy & rhinology Amanian, A., Hari, K., Habib, A., Dholoakia, S. S., Nayak, J., Thamboo, A. 2021

  View details for DOI 10.1002/alr.22761

  View details for PubMedID 33460303

• Oral Corticosteroids Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis Without Nasal Polyposis: A Randomized Clinical Trial. JAMA otolaryngology-- head & neck surgery Chang, M. T., Noel, J. n., Ayoub, N. F., Qian, Z. J., Dholakia, S. n., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2021

  Abstract

  Although oral corticosteroids are commonly prescribed following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) without nasal polyposis, there are little data to suggest that this is a beneficial practice.To assess the efficacy of oral corticosteroids following ESS in CRS without polyps.This prospective double-blinded, placebo-controlled, randomized noninferiority clinical trial conducted in a single academic tertiary rhinology practice included adults with CRS without polyps undergoing ESS. Of 81 patients recruited, 72 completed the study.Patients were randomized into 2 treatment groups: a 12-day postoperative taper of oral prednisone vs matched placebo tablets. All study patients also received a uniform 2-week postoperative regimen of oral antibiotics, fluticasone nasal spray, and saline rinses.The primary outcome measures were Sinonasal Outcome Test-22 (SNOT-22) scores and Lund-Kennedy endoscopy scores, collected preoperatively and postoperatively at 1 week, 1 month, 3 months, and 6 months. Scores were compared between treatment groups at each time point using longitudinal difference between treatment groups and analyzed using 2-way, repeated measures analysis of variance. Secondary outcome measures included treatment-related adverse effects.Overall, 72 patients (mean [SD] age, 49.4 [14.9] years; 36 men, 36 women) completed the study, with 33 in the prednisone arm and 39 in the placebo arm. When comparing longitudinal differences between treatment groups, there was no clinically meaningful difference observed in SNOT-22 total (F[4254] = 1.71, η2 = 0.01 [95% CI, 0.00-0.05]) or Lund-Kennedy scores (F[4247] = 1.23, η2 = 0.02 [95% CI, 0.00-0.50]). In SNOT-22 subdomain analyses, there was no clinically meaningful difference between treatment groups for rhinologic, extranasal rhinologic, ear/facial, or sleep subdomains. However, the prednisone group had worse longitudinal scores for psychological dysfunction compared with the placebo group (F[4254] = 3.18, η2 = 0.05 [95% CI, 0.02-0.09]). Reported adverse effects were similar between the 2 treatment groups.In this randomized clinical trial of patients with CRS without polyps, oral prednisone following ESS conferred no additional benefit over placebo in terms of SNOT-22 total scores, SNOT-22 rhinologic subscores, or Lund-Kennedy endoscopy scores up to 6 months after surgery. Patients receiving prednisone, however, did demonstrate worse SNOT-22 psychologic subdomain scores. These results suggest that the risks of oral corticosteroids may outweigh the benefits; thus use of oral corticosteroids after ESS for CRS without polyps should be carefully considered.ClinicalTrials.gov Identifier: NCT02748070.

  View details for DOI 10.1001/jamaoto.2021.0011

  View details for PubMedID 33662124

• Targeted replacement of full-length CFTR in human airway stem cells by CRISPR/Cas9 for pan-mutation correction in the endogenous locus. Molecular therapy : the journal of the American Society of Gene Therapy Vaidyanathan, S. n., Baik, R. n., Chen, L. n., Bravo, D. T., Suarez, C. J., Abazari, S. M., Salahudeen, A. A., Dudek, A. M., Teran, C. A., Davis, T. H., Lee, C. M., Bao, G. n., Randell, S. H., Artandi, S. E., Wine, J. J., Kuo, C. J., Desai, T. J., Nayak, J. V., Sellers, Z. M., Porteus, M. H. 2021

  Abstract

  Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction of the most common pathogenic mutation, there are many other pathogenic mutations throughout the CF gene. An autologous airway stem cell therapy in which the CFTR cDNA is precisely inserted into the CFTR locus may enable the development of a durable cure for almost all CF patients, irrespective of the causal mutation. Here, we use CRISPR/Cas9 and two adeno-associated viruses (AAV) carrying the two halves of the CFTR cDNA to sequentially insert the full CFTR cDNA along with a truncated CD19 (tCD19) enrichment tag in upper airway basal stem cells (UABCs) and human bronchial basal stem cells (HBECs). The modified cells were enriched to obtain 60-80% tCD19+ UABCs and HBECs from 11 different CF donors with a variety of mutations. Differentiated epithelial monolayers cultured at air-liquid interface showed restored CFTR function that was >70% of the CFTR function in non-CF controls. Thus, our study enables the development of a therapy for almost all CF patients, including patients who cannot be treated using recently approved modulator therapies.

  View details for DOI 10.1016/j.ymthe.2021.03.023

  View details for PubMedID 33794364

• Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow patterns in empty nose syndrome patients via computational fluid dynamics (CFD) modeling. International forum of allergy & rhinology Malik, J., Dholakia, S., Spector, B. M., Yang, A., Kim, D., Borchard, N. A., Thamboo, A., Zhao, K., Nayak, J. V. 2020

  Abstract

  BACKGROUND: Empty nose syndrome (ENS) is a controversial upper airway disorder most commonly associated with tissue loss from the inferior turbinates. The inferior meatus augmentation procedure (IMAP) has been shown to effectively reduce ENS symptoms in a durable manner, but the precise mechanisms that may govern this symptomatic improvement remain unknown.METHODS: Five patients with ENS who underwent bilateral IMAP via submucosal costal cartilage implant were assessed. Pre-implant and 6 months post-implant computed tomography (CT) imaging for each ENS patient was analyzed in a blinded fashion using computational fluid dynamics (CFD) modeling to investigate intrapatient changes in airflow parameters.RESULTS: Following surgery, ENS patients have significantly improved symptoms as indexed by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) scoring (pre-implant: 14.00 ± 4.06 [mean ± standard deviation]; 95% confidence interval [CI], 10.44 to 17.56; post-implant: 4.8 ± 2.77; 95% CI, 2.37 to 7.23; Cohen's d = 2.64; p = 0.02). Using CFD, a significant shift in nasal airflow patterns was observed, where airflow deviates away from the middle meatus upon hitting the implant (pre-implant: 67.13% ± 11.14%; 95% CI, 60.22% to 74.04%; post-implant: 46.18% ± 12.81%; 95% CI, 38.23% to 54.12%; d = 1.74; p < 0.05) toward the inferior meatus (pre-implant: 30.55% ± 11.29%; 95% CI, 23.55% to 37.55%; post-implant: 42.59% ± 9.60%; 95% CI, 36.63 to 48.54%; d = 1.14; p < 0.05). No significant changes were found in nasal resistance (pre-implant: 0.102 ± 0.015; 95% CI, 0.092 to 0.112 Pa*s/mL; post-implant: 0.105 ± 0.041; 95% CI, 0.081 to 0.130 Pa*s/mL). In addition, the improvement of ENS6Q scoring significantly correlated with percent reduction in aberrant airflow through the middle meatus (R2 = 0.60, p = 0.04).CONCLUSION: This study supports our prior working hypothesis that disordered vectors of nasal airflow congregate in the middle meatus contribute to ENS symptoms, not nasal resistance. Moreover, these data illuminate a paradoxical, but consistent, restoration of nasal airflow to the inferior meatus following the replacement of turbinate tissue volume in the inferior meatus via IMAP surgery, potentially due to the Coanda effect.

  View details for DOI 10.1002/alr.22720

  View details for PubMedID 33249769

• ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs. Nature communications Lee, I. T., Nakayama, T., Wu, C., Goltsev, Y., Jiang, S., Gall, P. A., Liao, C., Shih, L., Schurch, C. M., McIlwain, D. R., Chu, P., Borchard, N. A., Zarabanda, D., Dholakia, S. S., Yang, A., Kim, D., Chen, H., Kanie, T., Lin, C., Tsai, M., Phillips, K. M., Kim, R., Overdevest, J. B., Tyler, M. A., Yan, C. H., Lin, C., Lin, Y., Bau, D., Tsay, G. J., Patel, Z. M., Tsou, Y., Tzankov, A., Matter, M. S., Tai, C., Yeh, T., Hwang, P. H., Nolan, G. P., Nayak, J. V., Jackson, P. K. 2020; 11 (1): 5453

  Abstract

  The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

  View details for DOI 10.1038/s41467-020-19145-6

  View details for PubMedID 33116139

• Ethacridine inhibits SARS-CoV-2 by inactivating viral particles in cellular models. bioRxiv : the preprint server for biology Li, X., Lidsky, P., Xiao, Y., Wu, C. T., GarciaKnight, M., Yang, J., Nakayama, T., Nayak, J. V., Jackson, P. K., Andino, R., Shu, X. 2020

  Abstract

  More than a million people have now died from COVID-19, because of infection with the SARS-CoV-2 coronavirus. Currently, the FDA has approved remdesivir, an inhibitor of SARS-CoV-2 replication, to treat COVID-19, though very recent data from WHO showed little if any COVID19 protective effect. Here we report that ethacridine, a safe and potent antiseptic use in humans, effectively inhibits SARS-CoV-2, at very low concentrations (EC 50 ~ 0.08 μ M). Ethacridine was identified through a high-throughput screening of an FDA-approved drug library in living cells using a fluorescent assay. Interestingly, the main mode of action of ethacridine is to inactivate virus particles, preventing binding to the host cells. Thus, our work has identified a potent drug with a distinct mode of action against SARS-CoV-2.

  View details for DOI 10.1101/2020.10.28.359042

  View details for PubMedID 33140048

  View details for PubMedCentralID PMC7605555

• Outcomes in Treatment of Rhinosinusitis in the Setting of Medication Induced Immunosuppression. American journal of rhinology & allergy Alapati, R., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2020: 1945892420947932

  Abstract

  BACKGROUND: There is no data currently available to direct nuanced treatment for recurrent acute and chronic rhinosinusitis (RARS, CRS) in patients on daily, long term medications that suppress the immune system.OBJECTIVE: This study sought to evaluate the outcomes of different treatment pathways when treating immunosuppressed patients with chronic rhinosinusitis or recurrent acute rhinosinusitis.METHODS: A retrospective review of patients on immune suppressing medication presenting to a tertiary care center with RARS or CRS between the years 2014-2019 was completed. Patients were categorized into three groups based on treatment: medical management alone (MM), surgery after medical management (SAMM), or upfront surgery (US). Lund-Kennedy scores (LKS) and SNOT-22 scores were evaluated at baseline, 1 month, 3 months and 6 months from presentation.RESULTS: 68 patients met inclusion criteria, with no difference in demographics between groups. Patients who were treated with US and SAMM had significantly higher baseline LKS than those who were treated with MM alone (p=0.050, p=0.039). Once this difference was controlled for, there was no significant difference in overall change of LKS between the three groups over time. There was no significant disparity in baseline SNOT-22 scores between the three groups, but patients who underwent US had a significantly higher improvement in SNOT-22 from baseline compared to those undergoing MM alone (p=0.013).CONCLUSION: Patients experiencing chronic rhinosinusitis and recurrent acute rhinosinusitis who are taking immunosuppressive medication can significantly improve from both medical and surgical management, but upfront surgical management appears to result in greater disease resolution relative to medical management in those with CRS. More study is needed in the RARS patient population regarding upfront surgery versus medical management.

  View details for DOI 10.1177/1945892420947932

  View details for PubMedID 32746611

• In Reply: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic NEUROSURGERY Patel, Z. M., Fernandez-Miranda, J., Hwang, P. H., Nayak, J. V., Dodd, R. L., Sajjadi, H., Jackler, R. K. 2020; 87 (2): E162–E163

  View details for Web of Science ID 000593120500027

• Insertion of the CFTR cDNA in the Endogenous Locus in Airway Stem Cells Using CRISPR/Cas9 Restores CFTR Function to Wild-Type Levels in Differentiated Epithelia Vaidyanathan, S., Sellers, Z. M., Bravo, D. T., Le, W., Randell, S. H., Desai, T. J., Kuo, C. J., Nayak, J. V., Porteus, M. H. CELL PRESS. 2020: 569–70

  View details for Web of Science ID 000530089302407

• In Reply: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic. Neurosurgery Patel, Z. M., Fernandez-Miranda, J., Hwang, P. H., Nayak, J. V., Dodd, R. L., Sajjadi, H., Jackler, R. K. 2020

  View details for DOI 10.1093/neuros/nyaa156

  View details for PubMedID 32323725

• Letter: Precautions for Endoscopic Transnasal Skull Base Surgery During the COVID-19 Pandemic. Neurosurgery Patel, Z. M., Fernandez-Miranda, J., Hwang, P. H., Nayak, J. V., Dodd, R., Sajjadi, H., Jackler, R. K. 2020

  View details for DOI 10.1093/neuros/nyaa125

  View details for PubMedID 32293678

• Endoscopic endonasal resection of a large tuberculum sella meningioma. Neurosurgical focus: Video Mohyeldin, A., Nayak, J. V., Fernandez-Miranda, J. C. 2020; 2 (2): V3

  Abstract

  Over the past three decades, endoscopic endonasal surgery has unlocked new corridors to treat a wide spectrum of ventral skull base lesions. Tuberculum sella meningiomas represent one of the most ideal pathologies for ventral skull base access. Traditionally, these lesions were approached primarily through various subfrontal and frontal-lateral transcranial approaches that have unfortunately been shown to be associated with worsening visual decline postoperatively. The endoscopic endonasal approach is now being attempted by more surgeons and leverages an infrachiasmatic trajectory that provides direct access to the tuberculum sella where most of the vascular supply for these lesions can be taken early, facilitating more efficient surgical resection and mitigating the risk of optic nerve injury. Here we review a challenging case of a large (∼3 cm) tuberculum sella meningioma, encasing critical vessels off the circle of Willis and resected via an endoscopic endonasal approach. We discuss the technical nuances and relevant surgical anatomy of this approach and highlight important considerations in the safe and successful removal of these meningiomas. We show that certain tumors that appear to encase the supraclinoidal carotid artery can be fully resected via an endonasal approach with precise surgical technique and adequate exposure. Furthermore, this case illustrates the risk of injuring a key perforating vessel from the anterior communicating artery complex, called the subcallosal artery. Injury to this vessel is highly associated with tumors like the one presented here that extend into the suprachiasmatic space between the optic chiasm and the anterior communicating complex. Meticulous surgical dissection is required to preserve this perforating vessel as well as branches from the superior hypophyseal artery. Finally, we review our current closure techniques for these challenging approaches and discuss the use of a lumbar drain for 3 days to lower CSF leak rates. The video can be found here: https://youtu.be/mafyXi5B0MA.

  View details for DOI 10.3171/2020.4.FocusVid.19981

  View details for PubMedID 36284775

  View details for PubMedCentralID PMC9542388

• Indications and Outcomes for Patients With Limited Symptoms Undergoing Endoscopic Sinus Surgery. American journal of rhinology & allergy Rahman, A. S., Hwang, P. H., Alapati, R., Lin, Y., Nayak, J. V., Patel, Z. M., Yan, C. H. 2020: 1945892420912159

  View details for DOI 10.1177/1945892420912159

  View details for PubMedID 32168996

• Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial. Neurosurgery Yan, C. H., Rathor, A., Krook, K., Ma, Y., Rotella, M. R., Dodd, R. L., Hwang, P. H., Nayak, J. V., Oyesiku, N. M., DelGaudio, J. M., Levy, J. M., Wise, J., Wise, S. K., Patel, Z. M. 2020

  Abstract

  BACKGROUND: Endoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration.OBJECTIVE: To evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection.METHODS: In this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively.RESULTS: Eighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P=.02 and P=.01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P=.03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P=.04).CONCLUSION: Omega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

  View details for DOI 10.1093/neuros/nyz559

  View details for PubMedID 31950156

• The cotton test redistributes nasal airflow in patients with empty nose syndrome. International forum of allergy & rhinology Malik, J., Thamboo, A., Dholakia, S., Borchard, N. A., McGhee, S., Li, C., Zhao, K., Nayak, J. V. 2020

  Abstract

  BACKGROUND: Empty nose syndrome (ENS) remains a controversial disease primarily associated with inferior turbinate tissue loss. Cotton placement into the inferior meatus often alleviates ENS symptoms within minutes, but the physiologic explanation for this phenomenon is unknown. Computational fluid dynamics (CFD) was employed to evaluate the mechanisms of altered nasal airflow conferred by cotton testing.METHODS: Six ENS patients (12 sides) with pre-existing sinus computed tomography (CT) imaging were enrolled after marked symptomatic improvement (decrease in score on the Empty Nose Syndrome 6-Item Questionnaire [ENS6Q] of >7 points) with office-based cotton testing. The fashioned cotton plug was labeled in situ with iohexol contrast spray, and sinus CT was immediately obtained to detect cotton contouring in the inferior meatus. CT imaging from pre- and post-cotton placement was analyzed using comparative CFD techniques.RESULTS: After cotton placement, significant symptomatic improvement and reduced ENS6Q scores (16.8 ± 4.1 to 3.1 ± 2.4; p < 0.001) were recorded. Using CFD, cotton placement produced an expected 21% increase in upper airway resistance (p < 0.05). However, a significant shift in the nasal airflow distribution was also detected, with a transition of airflow vectors away from a middle meatus jetstream (-41%; p < 0.002).CONCLUSION: Objective CFD assessment confirmed that the cotton test not only increases nasal resistance, but also restores airflow distribution to the inferior meatus in symptomatic ENS patients. These results highlight the potential efficacy of cotton test in ENS patients and further bolster the utility of this tool in identifying appropriate candidates for the inferior meatus augmentation procedure.

  View details for DOI 10.1002/alr.22489

  View details for PubMedID 31951101

• Inferior Meatus Augmentation Procedure (IMAP) to Treat Empty Nose Syndrome: A Pilot Study. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Thamboo, A., Dholakia, S. S., Borchard, N. A., Patel, V. S., Tangbumrungtham, N., Velasquez, N., Huang, Z., Zarabanda, D., Nakayama, T., Nayak, J. V. 2020: 194599819900263

  Abstract

  Our understanding of empty nose syndrome (ENS) continues to evolve. Prior studies evaluating airway augmentation to treat ENS did not use validated disease-specific questionnaires, making the true impact of these surgeries unclear. We present a case series of 10 patients with ENS (11 procedures) who underwent the inferior meatus augmentation procedure (IMAP) between September 2014 and May 2017. Subjective outcomes of IMAP included comparisons of preoperative and postoperative assessments (1 week, 1 month, 3 months, 6 months) using the Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), and Sino-Nasal Outcome Test-22 (SNOT-22). The decrement in ENS6Q scores observed maintained statistical significance at 6 months (P ≤ .001). Similar results were achieved with PHQ-9, GAD-7, and SNOT-22 (P ≤ .01, P ≤ .01, P ≤ .001, respectively). IMAP can dramatically improve the quality of life of ENS patients regarding both ENS-specific symptoms and psychological well-being.

  View details for DOI 10.1177/0194599819900263

  View details for PubMedID 31935161

• Hemodynamic changes in patients undergoing office-based sinus procedures under local anesthesia. International forum of allergy & rhinology Chang, M. T., Jitaroon, K. n., Nguyen, T. n., Yan, C. H., Overdevest, J. B., Nayak, J. V., Hwang, P. H., Patel, Z. M. 2020; 10 (1): 114–20

  Abstract

  The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office-based endoscopic sinus procedures performed under local anesthesia.We conducted a prospective study of adults undergoing in-office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5-minute intervals throughout the procedure. Anxiety levels were scored using the State-Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric.Twenty-five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mmHg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mmHg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred.Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.

  View details for DOI 10.1002/alr.22460

  View details for PubMedID 31899857

• The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Chang, M. T., Hosseini, D. K., Song, S. H., Nayak, J. V., Patel, Z. M., Lee, J. Y., Hwang, P. H. 2020: 194599820917396

  Abstract

  We assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement.Retrospective chart review.Academic center.Patients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT-22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ-7 >3.5.In total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ-7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, P < .001), 6 weeks (17.8 ± 9.3, P < .001), 3 months (16.8 ± 8.5, P < .001), and 6 months (16.4 ± 7.9, P < .001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ-7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04-1.22; P = .030), higher preoperative SNOT-22 score (aOR, 1.02; 95% CI, 1.02-1.08; P = .001), higher preoperative SNOT-22 ear subscore (aOR, 1.27; 95% CI, 1.02-1.65; P = .034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22-4.92; P = .025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17-1.66; P = .008).ETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray.4.

  View details for DOI 10.1177/0194599820917396

  View details for PubMedID 32343633

• Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers. medRxiv : the preprint server for health sciences Lee, I. T., Nakayama, T. n., Wu, C. T., Goltsev, Y. n., Jiang, S. n., Gall, P. A., Liao, C. K., Shih, L. C., Schürch, C. M., McIlwain, D. R., Chu, P. n., Borchard, N. A., Zarabanda, D. n., Dholakia, S. S., Yang, A. n., Kim, D. n., Kanie, T. n., Lin, C. D., Tsai, M. H., Phillips, K. M., Kim, R. n., Overdevest, J. B., Tyler, M. A., Yan, C. H., Lin, C. F., Lin, Y. T., Bau, D. T., Tsay, G. J., Patel, Z. M., Tsou, Y. A., Tai, C. J., Yeh, T. H., Hwang, P. H., Nolan, G. P., Nayak, J. V., Jackson, P. K. 2020

  Abstract

  We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.

  View details for DOI 10.1101/2020.05.08.20092866

  View details for PubMedID 32511516

  View details for PubMedCentralID PMC7273284

• Nasal vestibular body treatment for recalcitrant nasal obstruction. International forum of allergy & rhinology Ibrahim, N. n., Tyler, M. A., Borchard, N. A., Rathor, A. n., Nayak, J. V. 2020

  Abstract

  The nasal vestibular body (NVB) is a recently reported dynamic swell body present in the inferolateral internal nasal valve. The contribution of NVB presence to persistent nasal obstruction, and effects of NVB treatment, are undefined.Thirty-five patients with recalcitrant nasal obstruction and NVB presence were retrospectively reviewed between 2013 and 2019, including 25 patients (48 sides) who had NVBs reduced via radiofrequency ablation (RFA) and 10 patients (20 sides) who had untreated NVBs. Posttreatment healing and complications were reviewed at early (<1 month) and late (mean, 7.3 months) time-points after RFA of the NVB. A subset of the NVB-treatment patients (18 of 25 patients) were compared with 10 NVB-control patients for pre-/posttreatment outcomes using 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomain scoring.NVBs were successfully reduced in 100% of cases (48 of 48 sides) over both time-points. Early sequelae of NVB treatment, such as local crusting (22 of 23, 95.6%) and bone exposure (4 of 23, 17.3%), resolved by the late time-point, with complete remucosalization (23 of 23, 100%) of all NVB treatment sites. No persistent pain, sensory loss, or pyriform aperture stenosis was noted from any patient/side. Significant reductions between mean pre- and postoperative SNOT-22 (-24, p = 0.001) and individual subdomain (-2, p = 002) scores were seen in the NVB-treatment patients compared to the reductions in NVB-controls (-8 and -1, respectively, both p > 0.001).NVB treatment using RFA is safe and highly effective, providing complete swell body reduction with only transient local morbidity. NVB presence contributes to persistent/recalcitrant nasal obstruction, with significant improvement in nasal airway function noted after NVB soft tissue reduction.

  View details for DOI 10.1002/alr.22463

  View details for PubMedID 32017469

• Management of Postsurgical Empty Nose Syndrome. Facial plastic surgery clinics of North America Talmadge, J., Nayak, J. V., Yao, W., Citardi, M. J. 2019; 27 (4): 465–75

  Abstract

  Empty nose syndrome (ENS) is a controversial condition associated with disruption of nasal airflow caused by excessive loss of turbinate tissue. ENS arises after total or near-total inferior turbinate resection. Patients present with intense fixation on the perception of nasal obstruction. Diagnostic tools to assess for empty nose syndrome include a validated patient questionnaire and the office cotton test. Treatment involves topical moisturization, behavioral/psychiatric assessment/treatment, and surgical reconstruction. Current data show promising long-term efficacy after surgical intervention. Postprocedural ENS is best prevented by minimizing inferior and middle turbinate tissue loss.

  View details for DOI 10.1016/j.fsc.2019.07.005

  View details for PubMedID 31587766

• Correlation between extent of sinus surgery, radiographic disease, and postoperative outcomes. Rhinology Ayoub, N., Walgama, E., Thamboo, A., Chitsuthipakorn, W., Patel, Z. M., Nayak, J. V., Hwang, P. H. 2019

  Abstract

  BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes.METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months.RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate.CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.

  View details for DOI 10.4193/Rhin19.213

  View details for PubMedID 31671433

• The Upper Airway Nasal Complex: Structural Contribution to Persistent Nasal Obstruction Williams, R., Patel, V., Chen, Y., Tangbumrungtham, N., Thamboo, A., Most, S. P., Nayak, J. V., Liu, S. C. SAGE PUBLICATIONS LTD. 2019: 171–77

  View details for DOI 10.1177/0194599819838262

  View details for Web of Science ID 000473507100024

• Environmental Triggers Associated With Empty Nose Syndrome Symptoms: A Cross-Sectional Study ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Manji, J., Patel, V. S., Nayak, J., Thamboo, A. 2019; 128 (7): 601–7

  View details for DOI 10.1177/0003489419833714

  View details for Web of Science ID 000470665300003

• Use of intranasal submucosal fillers as a transient implant to alter upper airway aerodynamics: implications for the assessment of empty nose syndrome Borchard, N. A., Dholakia, S. S., Yan, C. H., Zarabanda, D., Thamboo, A., Nayak, J. V. WILEY. 2019: 681–87

  View details for DOI 10.1002/alr.22299

  View details for Web of Science ID 000470911800015

• 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. 2019; 33 (3): 277–85

  View details for DOI 10.1177/1945892418823305

  View details for Web of Science ID 000470774400007

• Genome Edited Airway Stem Cells as a Durable Cell-Based Therapy to Treat Cystic Fibrosis Vaidyanathan, S., Sellers, Z. M., Bravo, D. T., Le, W., Nayak, J. V., Porteus, M. H. CELL PRESS. 2019: 83

  View details for Web of Science ID 000464381001006

• The Horizon Sign and Frontal Bar: Two Topographic Landmarks to Confirm Endoscopic Frontal Sinusotomy OTOLARYNGOLOGY-HEAD AND NECK SURGERY Walgama, E. S., Thamboo, A., Tangbumrungtham, N., Ayoub, N., Patel, Z. M., Nayak, J. V. 2019; 160 (4): 740–43

  View details for DOI 10.1177/0194599818825472

  View details for Web of Science ID 000463053500024

• Imaging predictors for malignant transformation of inverted papilloma Yan, C. H., Tong, C. L., Penta, M., Patel, V. S., Palmer, J. N., Adappa, N. D., Nayak, J. V., Hwang, P. H., Patel, Z. M. WILEY. 2019: 777–82

  View details for DOI 10.1002/lary.27582

  View details for Web of Science ID 000462650400015

• Microcurrent technology for rapid relief of sinus pain: a randomized, placebo-controlled, double-blinded clinical trial Maul, X. A., Borchard, N. A., Hwang, P. H., Nayak, J. V. WILEY. 2019: 352–56

  View details for DOI 10.1002/alr.22280

  View details for Web of Science ID 000468167600004

• The Upper Airway Nasal Complex: Structural Contribution to Persistent Nasal Obstruction. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Williams, R., Patel, V., Chen, Y., Tangbumrungtham, N., Thamboo, A., Most, S. P., Nayak, J. V., Liu, S. Y. 2019: 194599819838262

  Abstract

  OBJECTIVE: To determine the contribution of the nasal floor and hard palate morphology to nasal obstruction for nonresponders to prior intranasal surgery.STUDY DESIGN: Retrospective case-control study.SETTING: Tertiary academic center.METHODS: Institutional review board-approved, retrospective institutional database analysis was obtained of a cohort of 575 patients who presented with nasal obstruction over a 21-year period. Of the patients, 89 met inclusion criteria: 52 were placed into the experimental group, defined as having persistent nasal obstruction following endoscopic sinus surgery (ESS), septoplasty, nasal valve repair, and/or turbinoplasty using validated subjective questionnaires, and 37 were placed into the control group, defined as having resolution of subjective nasal obstruction. Computed tomography imaging was presented to 3 blinded experts, who measured numerous nasal airway and hard palate morphology parameters, including anterior nasal floor width, anterior maxillary angle, maxilla width, anterior nasal floor width, and palatal vault height. Standard demographic information, comorbidities, perioperative 22-item Sinonasal Outcome Test (SNOT-22), and follow-up time were also assessed. Wilcox rank sum analysis or t test was performed where appropriate.RESULTS: Follow-up ranged from 2 to 36 months following surgical intervention. Several skeletal characteristics within the upper airway were significantly associated with persistent nasal obstruction, including acute maxillary angle ( P = .035), narrow maxillary width ( P = .006), and high arched palate ( P = .004).CONCLUSION: Persistent nasal obstruction may be seen in patients with narrow, high arched hard palate despite prior nasal surgical intervention and may benefit from additional skeletal remodeling procedures such as maxillary expansion.

  View details for PubMedID 30909809

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

• Patient-Reported Outcome Measures and Provocative Testing in the Workup of Empty Nose Syndrome-Advances in Diagnosis: A Systematic Review. American journal of rhinology & allergy Gill, A. S., Said, M. n., Tollefson, T. T., Strong, E. B., Nayak, J. V., Steele, T. O. 2019: 1945892419880642

  View details for DOI 10.1177/1945892419880642

  View details for PubMedID 31594386

• The effect of topical epinephrine 1:1000 with and without infiltration of 1% lidocaine with epinephrine 1:100,000 on endoscopic surgical field visualization: a double-blind randomized controlled study. International forum of allergy & rhinology Tangbumrungtham, N. n., Hwang, P. H., Maul, X. n., Borchard, N. A., Dholakia, S. S., Patel, Z. M., Nayak, J. V., Choby, G. n. 2019

  Abstract

  The objective of this study is to determine whether the infiltration of 1% lidocaine with 1:100,000 epinephrine in addition to topical application of 1:1000 epinephrine significantly improves surgical field grading scale score over topical 1:1000 epinephrine alone.A prospective, double-blind, randomized, controlled study was performed of 40 patients undergoing bilateral endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Patients were enrolled and randomly assigned to receive infiltration with 1% lidocaine with 1:100,000 epinephrine on 1 side of the nasal cavity vs plain saline on the other side in preparation for ESS. Both groups received topical application of 1:1000 epinephrine. Surgical videos were recorded and Wormald surgical field grading scale was assigned by 2 blinded reviewers. The number of extra 1:1000 epinephrine pledgets used during the surgery, estimated blood loss, and surgical duration were also recorded.There were no statistically significant differences in Wormald surgical field grading scale, number of extra pledgets used, or estimated blood loss between the nasal cavity side infiltrated with 1% lidocaine with 1:100,000 epinephrine in comparison to infiltration with saline. The side infiltrated with 1% lidocaine with 1:100,000 epinephrine had a reduced operative time compared to the side infiltrated with saline (p = 0.002). There were no differences in postoperative bleeding from questionnaire completed by patient at the first postoperative visit.Addition of infiltration of 1% lidocaine with epinephrine 1:100,000 to topical application of epinephrine 1:1000 for preparation of ESS does not significantly improve surgical field of view compared to topical epinephrine alone.

  View details for DOI 10.1002/alr.22468

  View details for PubMedID 31671251

• High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia. Cell stem cell Vaidyanathan, S. n., Salahudeen, A. A., Sellers, Z. M., Bravo, D. T., Choi, S. S., Batish, A. n., Le, W. n., Baik, R. n., de la O, S. n., Kaushik, M. P., Galper, N. n., Lee, C. M., Teran, C. A., Yoo, J. H., Bao, G. n., Chang, E. H., Patel, Z. M., Hwang, P. H., Wine, J. J., Milla, C. E., Desai, T. J., Nayak, J. V., Kuo, C. J., Porteus, M. H. 2019

  Abstract

  Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Mortality in CF patients is mostly due to respiratory sequelae. Challenges with gene delivery have limited attempts to treat CF using in vivo gene therapy, and low correction levels have hindered ex vivo gene therapy efforts. We have used Cas9 and adeno-associated virus 6 to correct the ΔF508 mutation in readily accessible upper-airway basal stem cells (UABCs) obtained from CF patients. On average, we achieved 30%-50% allelic correction in UABCs and bronchial epithelial cells (HBECs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentiated epithelia. Furthermore, we successfully embedded the corrected UABCs on an FDA-approved porcine small intestinal submucosal membrane (pSIS), and they retained differentiation capacity. This study supports further development of genetically corrected autologous airway stem cell transplant as a treatment for CF.

  View details for DOI 10.1016/j.stem.2019.11.002

  View details for PubMedID 31839569

• 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

  Abstract

  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 Thamboo, A., Rathor, A., Borchard, N. A., Nayak, J. V., Hwang, P. H., Patel, Z. M. WILEY. 2018: 1389–94

  View details for DOI 10.1002/alr.22184

  View details for Web of Science ID 000453516400004

• 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; 8 (10): 1162–68

  View details for DOI 10.1002/alr.22156

  View details for Web of Science ID 000446274900013

• Comparison of outcomes following culture-directed vs non-culture-directed antibiotics in treatment of acute exacerbations of chronic rhinosinusitis Yan, C. H., Tangbumrungtham, N., Maul, X. A., Ma, Y., Nayak, J. V., Hwang, P. H., Patel, Z. M. WILEY. 2018: 1028–33

  View details for DOI 10.1002/alr.22147

  View details for Web of Science ID 000443132000008

• 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

  Abstract

  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

• The "Cross-court draf IIb" procedure for advanced nasal septum or frontal sinus pathology and nasal septum pathology. The Laryngoscope Choby, G., Nayak, J. V. 2018; 128 (7): 1527-1530

  View details for DOI 10.1002/lary.27016

  View details for PubMedID 29271490

• Nose blowing after endoscopic sinus surgery does not adversely affect outcomes LARYNGOSCOPE Ayoub, N., Chitsuthipakorn, W., Nayak, J. V., Patel, Z. M., Hwang, P. H. 2018; 128 (6): 1268–73

  View details for DOI 10.1002/lary.26907

  View details for Web of Science ID 000434179100010

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  View details for DOI 10.1016/j.wneu.2017.08.058

  View details for Web of Science ID 000415874900003

• 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

  Abstract

  Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recently, endoscopic transsphenoidal approaches have been increasingly used; however, few case series exist in the pediatric population.A retrospective review of patients (aged <18 years) undergoing endoscopic transsphenoidal resection of craniopharyngiomas between 1995 and 2016 was performed. Preoperative data included presenting symptoms, tumor size, location, and components. Postoperative outcomes included symptom resolution, visual outcomes, endocrine outcomes, disease recurrence, and major complications.Sixteen pediatric patients with mean age of 11.0 years (range, 5-15 years) were included. The median follow-up time was 56.2 months. Mean maximal tumor diameter was 3.98 cm. Most of the tumors had suprasellar (93.8%) and intrasellar (68.8%) components. The gross total resection rate was 93.8%. The most common presenting symptoms were vision changes (81.3%) and increased intracranial pressure (56.3%). Most patients (66.7%) had their presenting symptoms resolved by their first postoperative visit. Vision improved or remained normal in 69.2% of patients. Postoperatively, new incidence of panhypopituitarism or diabetes insipidus developed in 63.6% and 46.7% of patients, respectively. New hypothalamic obesity developed in 28.6% of patients. The postoperative cerebrospinal fluid leak rate was 18.8%. One patient died of intraventricular hemorrhage postoperatively. The major complication rate was 12.5%. Disease recurrence occurred in 1 patient with gross total resection (6.3%).Endoscopic transsphenoidal resection for craniopharyngiomas can achieve high rates of total resection with low rates of disease recurrence in larger tumors than previously described. However, hypothalamic-pituitary dysfunction and cerebrospinal fluid leak remain significant postoperative morbidities.

  View details for DOI 10.1016/j.wneu.2017.08.058

  View details for PubMedID 28838874

• 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

  Abstract

  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-+

  Abstract

  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

• Efficacy of endoscopic sinus surgery for chronic rhinosinusitis following primary radiotherapy and concurrent chemotherapy for nasopharyngeal carcinoma INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Ayoub, N., Walgama, E., Thamboo, A., Nayak, J. V., Hwang, P. H. 2017; 7 (11): 1045–51

  Abstract

  Chronic rhinosinusitis (CRS) is a downstream complication following radiotherapy or chemoradiation for nasopharyngeal carcinoma (NPC). Endoscopic sinus surgery (ESS) is an accepted therapy for medically refractory CRS, but its efficacy in addressing CRS symptoms in patients with previously irradiated NPC is unclear.All patients at the Stanford Sinus Center with a history of radiation therapy or chemoradiation for NPC between 2006 and 2015 were reviewed. Patients without antecedent CRS prior to NPC treatment (n = 26) were retrospectively divided into 2 cohorts based on whether they developed postirradiation CRS and underwent ESS (surgical group, n = 13) or did not develop CRS (control, n = 13). Demographic and clinical characteristics were collected, and temporal changes in 22-item Sino-Nasal Outcome Test (SNOT-22) score were compared.The median time following primary irradiation to initial presentation was 6.8 and 6.5 years in the surgical and control groups, respectively. The surgical cohort had statistically greater baseline SNOT-22 scores than the control group (45 vs 14, p = 0.0198). At 6 to 12 months postoperatively, the surgical group demonstrated statistically significant and clinically meaningful improvements in SNOT-22 scores when compared to controls (15-point decrease vs 0, p = 0.0040), ultimately resulting in similar SNOT-22 scores for both groups (28 vs 18, p = 0.3687). The rhinologic, extranasal, and ear/face subdomain scores of the surgical group were significantly greater than those of the control group preoperatively (rhinologic: p = 0.0010; extranasal: p = 0.0179; ear/face: p = 0.0068), but these disparities resolved postoperatively (rhinologic: p = 0.1461; extranasal: p = 0.3131; ear/face: p = 0.3401).ESS appears to effectively manage recalcitrant CRS symptoms in patients previously treated with radiation therapy and concurrent chemotherapy for NPC.

  View details for PubMedID 28806502

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

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

  Abstract

  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

• 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

  View details for DOI 10.1155/2017/6384586

  View details for Web of Science ID 000392538000001

• 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. n., Shih, L. C., Patel, Z. M., Nayak, J. V., Hwang, P. H. 2017

  Abstract

  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. n., Patel, V. S., Thamboo, A. n., Patel, Z. M., Nayak, J. V., Ma, Y. n., Choby, G. n., Hwang, P. H. 2017

  Abstract

  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

• 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

  Abstract

  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

  Abstract

  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

• 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-?

  Abstract

  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

• Evidence for a 'preinvasive' variant of fungal sinusitis: Tissue invasion without angioinvasion. World journal of otorhinolaryngology - head and neck surgery Paknezhad, H. n., Borchard, N. A., Charville, G. W., Ayoub, N. F., Choby, G. W., Thamboo, A. n., Nayak, J. V. 2017; 3 (1): 37–43

  Abstract

  Clinical experience has suggested the existence of an intermediate form of fungal sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and invasive fungal sinusitis (IFS). This fungal sinusitis variant demonstrates unhealthy mucosa by endoscopy with fungal invasion, but lacks angioinvasion microscopically, representing what clinically behaves as a 'pre-invasive' subtype of fungal sinusitis. Unlike non-IFS disease, patients with pre-invasive fungal sinusitis were still felt to require anti-fungal medications due to histologic presence of invasive fungus. While sharing some clinical features of IFS, these 'intermediate' patients were successfully spared extended and repeated surgical debridements given the microscopic findings, and have been successfully treated with shorter courses of antifungal therapy. These select patients have had favorable outcomes when managed in a judicious and semi-aggressive manner, in an undefined zone between the treatments for routine fungal ball and aggressive IFS.

  View details for PubMedID 29204577

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

  Abstract

  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

• 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

  Abstract

  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)

  Abstract

  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

• 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)

  View details for DOI 10.1172/jci.insight.88027

  View details for Web of Science ID 000387119700008

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

• Reply to: In reference to: Medical therapy vs surgery for recurrent acute rhinosinusitis INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Hwang, P. H., Costa, M. L., Psaltis, A. J., Nayak, J. V. 2015; 5 (12): 1186

  View details for PubMedID 26458500

• 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

  Abstract

  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

• 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): 1077-81

  Abstract

  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 PubMedID 26332403

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

• A Case of Stereotactic Radiation in Skull Base Solitary Fibrous Tumor: More Harm Than Good? JOURNAL OF NEUROLOGICAL SURGERY REPORTS Maria, P., Abuzeid, W. M., Nayak, J. V., Chang, S. D., Blevins, N. H. 2014; 75 (2): E214–E216

  View details for DOI 10.1055/s-0034-1387196

  View details for Web of Science ID 000215674900006

• 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

  Abstract

  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

• 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

  Abstract

  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

• 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

  Abstract

  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

• Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease. Otolaryngology--head and neck surgery : official journal of American Academy of 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

  Abstract

  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 PubMedID 25118195

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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-?

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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