Publications by authors named "Natasha Mirza"

63 Publications

Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing.

World J Otorhinolaryngol Head Neck Surg 2021 Feb 12. Epub 2021 Feb 12.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Background: Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction.

Objectives: The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers.

Methods: Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed.

Results: Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time-dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.

Conclusion: Healthcare workers with recent SARS-CoV-2 infection had reduced olfaction and normal gustation on self-administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.
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http://dx.doi.org/10.1016/j.wjorl.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879131PMC
February 2021

Iatrogenic Tracheal Injuries: Case Series and Review of the Literature.

ORL J Otorhinolaryngol Relat Spec 2021 9;83(2):123-126. Epub 2020 Dec 9.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Iatrogenic tracheal injuries are an uncommon but serious complication of endotracheal tube intubation. We present two cases that illustrate iatrogenic tracheal injuries presenting hours after the time of their injury. This report addresses the critical diagnostic evaluation and management of iatrogenic tracheal injuries resulting from endotracheal intubation.
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http://dx.doi.org/10.1159/000511712DOI Listing
December 2020

Auditory Feedback Control of Vocal Pitch in Spasmodic Dysphonia.

Laryngoscope 2020 Nov 10. Epub 2020 Nov 10.

Department of Otorhinolaryngology - Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: Hearing plays an important role in the maintenance of vocal control in normal individuals. In patients with spasmodic dysphonia (SD), however, the ability to maintain sustained control of phonation is impaired. The origins of SD are unknown, and it is unclear whether auditory feedback-dependent vocal control is compromised in these patients.

Study Design: Prospective case-control study.

Methods: We tested 15 SD patients and 11 age-matched controls. Voice recordings were performed while subjects repeated the vowel /e/ and auditory feedback of their vocal sounds was altered in real-time to introduce a pitch-shift (±2 semitones), presented back to subjects using headphones. Recordings were analyzed to determine voice changes following the pitch-shifted feedback. Results were further compared with patient demographics and subjective measures of dysphonia, including the Voice Handicap Index (VHI).

Results: Despite considerable pitch variability and vocal breaks, SD patients exhibited significantly higher average vocal pitch compensation than control subjects. SD patients also exhibited greater variability than controls. However, there were no significant correlations between vocal compensation and patient demographics, although there was a significant inverse correlation with VHI.

Conclusions: In this pilot study, patients with SD exhibited increased sensitivity to altered auditory feedback during sustained phonation. These results are consistent with recent theories of SD as a disorder of sensory-motor feedback processing, and suggest possible avenues for future investigation.

Level Of Evidence: 3 Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29254DOI Listing
November 2020

Current Practices in Endotracheal Tube Size Selection for Adults.

Laryngoscope 2020 Oct 29. Epub 2020 Oct 29.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: Intubation with inappropriately sized endotracheal tubes (ETT) can cause long-term tracheal and laryngeal injuries often requiring surgical intervention. Although tracheal size has been demonstrated to vary based on height and sex, it is unclear whether these guidelines are regularly implemented in patients undergoing endotracheal intubation. The objective of this study is to determine the rate of appropriate ETT size selection in patients undergoing intubation and assess provider decision making in ETT size selection.

Study Design: Retrospective cohort study.

Methods: The study population was all patients who underwent endotracheal intubation over a two-week period at a tertiary academic medical center. Data were collected on patient age, gender, height, BMI, comorbidities, ETT size, duration of intubation, bronchoscopies, and type of practitioner who performed the intubation. A height-based nomogram for ETT size selection was used to determine the recommended ETT size for each patient.

Results: One hundred five patients met the inclusion criteria. 22% of patients were intubated with an inappropriately large tube, defined as 1.0 mm larger than the recommended size. Women were more likely to be intubated with an inappropriately large ETT (OR = 13.58, P = .001), as were patients with height less than 160 cm (OR = 141, P = .001). Other factors related to disease severity, anticipation for bronchoscopy, and BMI were not risk factors for the use of inappropriately large ETT.

Conclusions: Although there is compelling evidence that height is a strong predictor of tracheal morphology and appropriate ETT size, height-based guidelines have yet to be universally adopted for ETT size selection. Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29192DOI Listing
October 2020

Gore-Tex implant extrusion following revision medialization thyroplasty: Case report and review of the literature.

World J Otorhinolaryngol Head Neck Surg 2020 Sep 19. Epub 2020 Sep 19.

Department of Otorhinolaryngology, Head & Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Objective: To review current literature and experience with Gore-TexⓇ implant extrusion following medialization thyroplasty, as well as to report the unique case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty.

Methods: Review of existing literature and description of personal experience with unique case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty.

Results: Review of existing literature found no prior reported cases of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Risk factors for implant extrusion include the pressure of the implant on insertion and the inability to secure the implant. Cases of implant extrusion can be managed operatively via an endoscopic or via an external open approach.

Conclusion: This is the first reported case of Gore-TexⓇ implant extrusion following revision medialization thyroplasty. Careful consideration should be given in revision medialization thyroplasty as additional implant material may cause increased pressure, a risk factor for implant extrusion.
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http://dx.doi.org/10.1016/j.wjorl.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502009PMC
September 2020

Airway management of angioedema patients during the COVID-19 pandemic.

World J Otorhinolaryngol Head Neck Surg 2020 Nov 5;6:S36-S39. Epub 2020 Jun 5.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, United States.

Importance: The COVID-19 pandemic is characterized by high transmissibility from patients with prolonged minimally- or asymptomatic periods, with a particularly increased risk of spread during aerosol-generating procedures, including endotracheal intubation.

Observations: All patients presenting with upper airway obstruction due to angioedema during this time should be carefully managed in a way that is safest for both patient and provider.

Conclusions: For patients requiring emergent airway management during the COVID-19 pandemic, minimization of aerosols while taking the necessary precautions to protect healthcare workers should are critical principles for their management.
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http://dx.doi.org/10.1016/j.wjorl.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274586PMC
November 2020

Virtual Dysphagia Evaluation: Practical Guidelines for Dysphagia Management in the Context of the COVID-19 Pandemic.

Otolaryngol Head Neck Surg 2020 09 26;163(3):455-458. Epub 2020 May 26.

Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

With encouraging signs of pandemic containment nationwide, the promise of return to a full range of clinical practice is on the horizon. Clinicians are starting to prepare for a transition from limited evaluation of emergent and urgent complaints to resumption of elective surgical procedures and routine office visits within the next few weeks to months. Otolaryngology as a specialty faces unique challenges when it comes to the COVID-19 pandemic due to the fact that a comprehensive head and neck examination requires aerosol-generating endoscopic procedures. Since the COVID-19 pandemic is far from being over and the future may hold other highly communicable infectious threats that may require similar precautions, standard approaches to the clinical evaluation of common otolaryngology complaints will have to be modified. In this communication, we present practical recommendations for dysphagia evaluation with modifications to allow a safe and comprehensive assessment.
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http://dx.doi.org/10.1177/0194599820931791DOI Listing
September 2020

Voice Restoration after Radiation and Supracricoid Partial Laryngectomy by Injection Augmentation of the Arytenoid.

J Voice 2019 Nov 29. Epub 2019 Nov 29.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Supracricoid partial laryngectomy (SCPL) is an organ-preserving surgical technique intended to achieve oncologic control of laryngeal cancer while maintaining laryngeal functions. Most patients who undergo SCPL achieve a serviceable voice. However, several factors can affect the function of the neoglottis after SCPL. We report the case of a 53-year-old male referred for near aphonia after undergoing SCPL for recurrent laryngeal carcinoma initially treated with radiation. Calcium hydroxylapatite injection augmentation of the right arytenoid was performed to assist neoglottic closure. Flexible laryngoscopy demonstrated greatly improved neoglottic closure postoperatively, and the patient's voice was successfully restored. This case demonstrates a novel technique for voice restoration in patients who have undergone partial laryngectomy.
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http://dx.doi.org/10.1016/j.jvoice.2019.11.002DOI Listing
November 2019

Long-Term Voice and Swallowing Outcomes for Oral and Oropharyngeal Cancer Following Primary or Adjuvant Chemoradiation.

Ann Otol Rhinol Laryngol 2019 Sep 21;128(9):802-810. Epub 2019 Apr 21.

1 Department of Otolaryngology-Head and Neck Surgery, Philadelphia, Pennsylvania, USA.

Objective: Chemoradiation (CRT) for nonlaryngeal head and neck cancer (HNC) can lead to voice and swallowing dysfunction. The purpose of this study was to examine voice and swallowing from the patient's perspective at least 5 years after treatment.

Design: Patient survey.

Methods: Twenty-eight patients treated with primary or adjuvant CRT at least 5 years ago (mean = 10.7 years, SD = 5.5, range, 5-28) completed a survey created based on previously validated questionnaires (the Patient Perception of Swallowing Function Questionnaire, PPSFQ; the Eating Assessment Tool, EAT-10; the Voice Handicap Index, VHI-10; the Voice Related Quality of Life, V-RQOL).

Results: Patients reported some voice and swallowing dysfunction (39% of V-RQOL scores in categories of fair, poor, or worst possible and 32% of VHI-10 scores ≥20 or greater than 50% of the maximum; 39% of PPSFQ scores greater than 50% of the maximum and 32% of EAT-10 scores ≥20 or 50% of the maximum). There was a correlation between V-RQOL and VHI-10 scores (Pearson product moment correlation coefficient r = .96, calculated probability value = 0), PPSFQ and EAT-10 scores (r = 0.87, = 0.8 × 10), as well as between V-RQOL and PPSFQ/EAT-10 scores (r = .94, = 0), VHI-10 and PPSFQ/EAT-10 scores (r = .97, = 0).

Conclusions: Perceived voice and swallowing dysfunction following CRT for nonlaryngeal HNC can persist or worsen beyond 5 years.
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http://dx.doi.org/10.1177/0003489419842256DOI Listing
September 2019

Spontaneous Giant Laryngeal Granuloma in the Absence of Laryngeal Injury.

J Voice 2020 Jan 20;34(1):162.e1-162.e3. Epub 2018 Sep 20.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA. Electronic address:

The etiology of laryngeal granuloma can typically be attributed to endotracheal intubation, vocal abuse, or gastroesophageal reflux disease. There is a strong male predominance, except in cases due to intubation, where incidence is higher in women. We report a case of spontaneous development of multiple granulomas in a female with no history of intubation who presented with hoarseness and massive bilateral supraglottic masses obscuring her glottis. The disparity between the massive lesions and asymptomatic reflux highlights the need for further research in the pathophysiology of laryngeal granulomas.
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http://dx.doi.org/10.1016/j.jvoice.2018.08.013DOI Listing
January 2020

Taste acceptability of thickening agents.

World J Otorhinolaryngol Head Neck Surg 2018 Jun 21;4(2):145-147. Epub 2018 Jul 21.

Department of Otorhinolaryngology Head and Neck Surgery, The University of Pennsylvania, Philadelphia, PA, USA.

Objective: Patients with dysphagia are often unable to manage secretions and liquids, necessitating the use of commercial thickeners to decrease the likelihood of aspiration. This study aims to evaluate the effect of commercially available thickeners on hedonic perception of various liquids.

Methods: Forty subjects without preexisting dysphagia or anosmia were recruited from a tertiary care otorhinolaryngology clinic over a five-month period. Participants were presented with samples of three unthickened liquids (ice water, chilled ginger ale, and hot coffee) and their thickened counterparts and asked to rate the taste acceptability of the liquids on an 11-point visual analog scale. The study was reviewed by the hospital's Institutional Review Board and determined to be IRB exempt.

Results: A statistically significant preference for unthickened liquids over their thickened counterpart was observed across flavors ( < 0.0001). Of the thickened liquid samples, study participants expressed the strongest preference for thickened ginger ale.

Conclusion: Thickened liquids are perceived as significantly less palatable than their unthickened counterparts, although ginger ale may be better tolerated when thickened than coffee or water. Providers should be aware of the impact of thickeners on taste acceptability when counseling patients with dysphagia.
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http://dx.doi.org/10.1016/j.wjorl.2018.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074016PMC
June 2018

Diagnostic utility of flexible fiberoptic nasopharyngolaryngoscopy recorded onto a smartphone: A pilot study.

World J Otorhinolaryngol Head Neck Surg 2018 Jun 23;4(2):135-139. Epub 2018 Jun 23.

Hospitals of the University of Pennsylvania, Philadelphia, PA, USA.

Objectives: To evaluate the diagnostic accuracy of flexible fiberoptic examinations of the larynx recorded onto smartphones.

Methods: Prospective, blinded study of inpatients requiring laryngoscopy. A live exam was performed, then a smartphone was attached to the endoscope using a novel coupling device and the same examination was recorded. The live and recorded exams were evaluated by two laryngologists, each blinded to the findings of the other.

Results: Eighteen subjects were evaluated. Evaluation of airway patency was identical (Kappa = 1.0 [1, 1]). Evaluation of vocal cord motion was identical for 14 subjects: 9 normal, 3 paretic, 2 paralytic (Kappa = 0.69 [0.38, 1]).

Conclusion: There is high correlation between laryngeal diagnoses using live flexible fiberoptic laryngoscopy and recordings using a coupling device to transfer the recordings on to smartphones. Critical findings such as airway patency and vocal fold motion showed the highest correlation.
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http://dx.doi.org/10.1016/j.wjorl.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074017PMC
June 2018

Geriatric Otolaryngology.

Otolaryngol Clin North Am 2018 08;51(4):xvii-xviii

Otolaryngology, Head and Neck Surgery, Stanford University, Comprehensive Otolaryngology, Adult Otolaryngology, 801 Welch Road, Second Floor, Palo Alto, CA 94305, USA. Electronic address:

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http://dx.doi.org/10.1016/j.otc.2018.04.002DOI Listing
August 2018

Influences of temporal lobe epilepsy and temporal lobe resection on olfaction.

J Neurol 2018 Jul 16;265(7):1654-1665. Epub 2018 May 16.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.
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http://dx.doi.org/10.1007/s00415-018-8891-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239967PMC
July 2018

High-Level Disinfection of Otorhinolaryngology Clinical Instruments: An Evaluation of the Efficacy and Cost-effectiveness of Instrument Storage.

Otolaryngol Head Neck Surg 2018 01 24;158(1):163-166. Epub 2017 Oct 24.

1 Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objectives Despite increasing interest in individual instrument storage, risk of bacterial cross-contamination of otorhinolaryngology clinic instruments has not been assessed. This study is the first to determine the clinical efficacy and cost-effectiveness of standard high-level disinfection and clinic instrument storage. Methods To assess for cross-contamination, surveillance cultures of otorhinolaryngology clinic instruments subject to standard high-level disinfection and storage were obtained at the start and end of the outpatient clinical workday. Rate of microorganism recovery was compared with cultures of instruments stored in individual peel packs and control cultures of contaminated instruments. Based on historical clinic data, the direct allocation method of cost accounting was used to determine aggregate raw material cost and additional labor hours required to process and restock peel-packed instruments. Results Among 150 cultures of standard high-level disinfected and co-located clinic instruments, 3 positive bacterial cultures occurred; 100% of control cultures were positive for bacterial species ( P < .001). There was no statistical difference between surveillance cultures obtained before and after the clinic day. While there was also no significant difference in rate of contamination between peel-packed and co-located instruments, peel packing all instruments requires 6250 additional labor hours, and conservative analyses place the cost of individual semicritical instrument storage at $97,852.50 per year. Discussion With in vitro inoculation of >200 otorhinolaryngology clinic instruments, this study demonstrates that standard high-level disinfection and storage are equally efficacious to more time-consuming and expensive individual instrument storage protocols, such as peel packing, with regard to bacterial contamination. Implications for Practice Standard high-level disinfection and storage are equally effective to labor-intensive and costly individual instrument storage protocols.
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http://dx.doi.org/10.1177/0194599817738977DOI Listing
January 2018

Invasive Aspergillus Laryngotracheobronchitis in an Adult with Primary CNS Lymphoma.

Mycopathologia 2017 Aug 17;182(7-8):733-737. Epub 2017 Feb 17.

Department of Otorhinolaryngology, Head and Neck Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA, 19104, USA.

Invasive aspergillosis can be difficult to diagnose, and early recognition and initiation of therapy is imperative for improving patient outcomes. A case of invasive Aspergillus laryngotracheobronchitis is presented here with a review of the relevant literature. A 58-year-old male undergoing treatment for CNS lymphoma presented with neutropenic sepsis and acute respiratory distress requiring intubation. Following extubation, he reported persistent hoarseness for 1-month duration and he was found to have pseudomembranous plaques and ulcers of the larynx, trachea, and right mainstem bronchus consistent with Aspergillus laryngotracheobronchitis. Invasive Aspergillus laryngotracheobronchitis should be considered in immunocompromised patients presenting with persistent hoarseness.
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http://dx.doi.org/10.1007/s11046-017-0123-yDOI Listing
August 2017

Idiopathic First Bite Syndrome.

J Oral Maxillofac Surg 2016 May 3;74(5):872. Epub 2016 Feb 3.

Philadelphia, PA.

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http://dx.doi.org/10.1016/j.joms.2015.12.024DOI Listing
May 2016

Influences of age, tongue region, and chorda tympani nerve sectioning on signal detection measures of lingual taste sensitivity.

Physiol Behav 2016 Mar 17;155:202-7. Epub 2015 Dec 17.

Smell and Taste Center, Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Although the ability to taste is critical for ingestion, nutrition, and quality of life, a clear understanding of the influences of age, sex, and chorda tympani (CT) resection on taste function in different regions of the anterior tongue is generally lacking. In this study we employed criterion-free signal detection analysis to assess electric and chemical taste function on multiple tongue regions in normal individuals varying in age and sex and in patients with unilateral CT resections. The subjects were 33 healthy volunteers, ranging from 18 to 87 years of age, and 9 persons, 27 to 77 years of age, with unilateral CT lesions. The influences of age, sex, tongue region, and chorda tympani resections on signal detection sensitivity (d') and response bias (β) measures was assessed in 16 tongue regions to weak electric currents and solutions of sucrose, sodium chloride, and caffeine. Significant age-related decrements in d' were found for sucrose (p=0.012), sodium chloride (p=0.002), caffeine (p=0.006), and electric current (EC) (p=0.0001). Significant posterior to anterior, and medial to lateral, gradients of increasing performance were present for most stimuli. β was larger on the anterior than the posterior tongue for the electrical stimulus in the youngest subjects, whereas the opposite was true for sucrose in the oldest subjects. No sex differences were apparent. d' was depressed ipsilateral to the CT lesion side to varying degrees in all tongue regions, with the weakest influences occurring on the medial and anterior tongue. CT did not meaningfully influence β. This study is the first to employ signal detection analysis to assess the regional sensitivity of the tongue to chemical and electrical stimuli. It clearly demonstrates that tongue regions differ from one another in terms of their age-related sensitivity and their susceptibility to CT lesions.
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http://dx.doi.org/10.1016/j.physbeh.2015.12.014DOI Listing
March 2016

IL-1 Receptor Antagonist Inhibits Early Granulation Formation.

Ann Otol Rhinol Laryngol 2016 Apr 1;125(4):284-9. Epub 2015 Nov 1.

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Purpose: Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers.

Methods: Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra-treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction.

Results: There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-β and IL-1β between the treated and untreated specimens.

Conclusions: Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.
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http://dx.doi.org/10.1177/0003489415610588DOI Listing
April 2016

Trauma-induced schwannoma of the recurrent laryngeal nerve after thyroidectomy.

Laryngoscope 2016 06 30;126(6):1408-10. Epub 2015 Sep 30.

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Laryngeal schwannomas are rare, benign tumors, most often arising from the superior laryngeal nerve. We describe a case of a 68-year-old female with a laryngeal schwannoma of the recurrent laryngeal nerve after traumatic injury. We postulate that trauma to the recurrent laryngeal nerve during thyroidectomy or thyroplasty incited growth of a nerve sheath tumor. This is the first reported case of a trauma-induced schwannoma of the recurrent laryngeal nerve and second case of a recurrent laryngeal nerve schwannoma. Although rare, this case demonstrates that these tumors should be considered during workup of vocal cord paresis after surgery or failed thyroplasty. Laryngoscope, 126:1408-1410, 2016.
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http://dx.doi.org/10.1002/lary.25697DOI Listing
June 2016

First bite syndrome: Our experience with intraparotid injections with botulinum toxin type A.

Laryngoscope 2016 Jan 15;126(1):104-7. Epub 2015 Sep 15.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Objectives/hypothesis: First bite syndrome is the sudden onset of acute and severe pain in the parotid region at the initiation of mastication. Although it generally lasts less than a minute, it is disabling for these individuals and leads to a fear of oral intake. It is typically seen after parapharyngeal or deep parotid space surgery. Intraparotid injection of botulinum toxin A (BTA) has been suggested as a treatment for this condition, but there is little supporting literature to this effect. The purpose of this study is to document our experience using this treatment method for first bite syndrome.

Study Design: Retrospective case review.

Methods: Five patients with first bite syndrome, developed after parapharyngeal space surgery, were treated by multisite injection of BTA into the parotid gland. Between 17.5 and 50 total U of BTA were injected into four or more sites in the parotid region. The patients were then followed up every 4 months.

Results: Three of five patients reported a significant improvement in symptoms at the 4-month follow-up visit, although complete resolution was not reported. One patient reported only moderate improvement, and despite two series of injections there was no improvement in one patient, leading us to question our initial diagnosis.

Conclusions: Unilateral BTA injection into the affected parotid gland produces a decrease in the severity of symptoms. It is a safe and viable noninvasive treatment for this difficult to treat condition and may lead to permanent resolution of symptoms in some patients.
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http://dx.doi.org/10.1002/lary.25571DOI Listing
January 2016

Anesthetic Management for Laser Excision of Ball-Valving Laryngeal Masses.

Case Rep Anesthesiol 2015 24;2015:875053. Epub 2015 May 24.

Department of Anesthesiology & Critical Care, Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, The University of Pennsylvania, PA 19104, USA.

A 47-year-old obese woman with GERD and COPD presents for CO2-laser excision of bilateral vocal fold masses. She had a history of progressive hoarseness and difficulty in breathing. Nasopharyngeal laryngoscopy revealed large, mobile, bilateral vocal cord polyps that demonstrated dynamic occlusion of the glottis. We describe the airway and anesthetic management of this patient with a topicalized C-MAC video laryngoscopic intubation using a 4.5 mm Xomed Laser Shield II endotracheal tube. We examine the challenges of anesthetic management unique to the combined circumstances of a ball-valve lesion and the need for a narrow-bore laser compatible endotracheal tube.
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http://dx.doi.org/10.1155/2015/875053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458295PMC
June 2015

Anticholinergic Use Is a Major Risk Factor for Dysphonia.

Ann Otol Rhinol Laryngol 2015 Oct 5;124(10):797-802. Epub 2015 May 5.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: We hypothesize that many cases of dysphonia of unclear etiology are a form of sicca caused by anticholinergic medication use, and we aim to determine their association.

Study Design: This was a cross-sectional study conducted over a 6-month time period. Participants were drawn from a tertiary care laryngology practice within an academic institution.

Methods: One hundred forty-nine patients met inclusion criteria. Patients rated the symptom of chronic hoarseness; scores were compared with participants' medication lists, comorbidities, age, and sex, and a multivariate logistic regression model was developed. Significance was set at P<.05. As a secondary analysis, participants rated a variety of other symptoms using the Voice Handicap Index-10, Reflux Symptom Index, and the GRBAS scale, which were likewise compared to anticholinergic use.

Results: Any patient taking at least 1 anticholinergic medication had a 2.32 increased odds (P=.03) of experiencing hoarseness. If the patient was taking 2 or more anticholinergic medications, those odds rose to 4.52 (P=.009).

Conclusion: This is the first study, to our knowledge, that implicates medication use as a major risk factor for dysphonia of unclear etiology. An awareness of this association is invaluable when attributing cause to hoarseness and when considering treatment options.
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http://dx.doi.org/10.1177/0003489415585867DOI Listing
October 2015

Influences of hormone replacement therapy on olfactory and cognitive function in postmenopausal women.

Neurobiol Aging 2015 Jun 10;36(6):2053-9. Epub 2015 Mar 10.

Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA.

Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone replacement therapy (HRT) may protect against Alzheimer's disease in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. A total of three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories. Serum levels of reproductive hormones were obtained for all subjects; APOE-ε4 haplotype was determined for 77 women. National Adult Reading Test and Odor Memory/Discrimination Test scores were positively influenced by HRT. Odor Identification and Odor Memory/Discrimination Test scores were lower for women who scored poorly on a delayed recall test, a surrogate for mild cognitive impairment. The Wechsler Adult Intelligence Scale, Revised, as a Neuropsychological Instrument Spatial Span Backwards Test scores were higher in women receiving estrogen and progestin HRT and directly correlated with serum testosterone levels, the latter implying a positive effect of testosterone on spatial memory. APOE-ε4 was associated with poorer odor threshold test scores. These data suggest that HRT positively influences a limited number of olfactory and cognitive measures during menopause.
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http://dx.doi.org/10.1016/j.neurobiolaging.2015.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640930PMC
June 2015

Inflammatory protein expression in human subglottic stenosis tissue mirrors that in a murine model.

Ann Otol Rhinol Laryngol 2014 Jan;123(1):65-70

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Objectives: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model.

Methods: Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction.

Results: The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor β1, interleukin 1β, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ.

Conclusions: This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.
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http://dx.doi.org/10.1177/0003489414521146DOI Listing
January 2014

Presentation and publication rates among women and men at AAO-HNS meetings.

ORL J Otorhinolaryngol Relat Spec 2012 5;74(6):325-9. Epub 2013 Jan 5.

Department of Otolaryngology, Head and Neck Surgery, Weill Cornell Medical College, New York, N.Y. 10021, USA.

Objective: We attempted to assess the percentages of abstracts submitted to annual American Academy of Otolaryngology, Head and Neck Surgery (AAO-HNS) meetings from 2000 to 2004 by both women and men. We sought to determine the subsequent peer-reviewed overall publication rates for all submissions. We also studied trends of submission among female presenters and compared them to males.

Study Design: Cross-sectional study.

Setting: Tertiary academic medical center.

Methods: 2,463 total abstracts presented between 2000 and 2004 were searched in the computerized databases Medline and Pubmed in 2008. The published articles were examined by reviewers to assess publication rate, time to publication, gender of authorship and subspecialty of publication.

Results: 1,413 (57.35%) posters and 1,051 (42.65%) oral presentations were presented from 2000 to 2004. Of the 1,413 posters presented, 275 (19.46%) were presented by female first authors. The female first-author poster publication rate was 33.81%, while the male first-author poster publication rate was 36.99% (p = 0.353). Of 1,051 oral presentations, 154 (14.65%) were presented by female first authors. The male first-author oral presentation publication rate was 60.98%, while the female first-author oral presentation publication rate was 59.09% (p = 0.657). There were no statistical differences in time to publication for posters (p = 0.796) or oral presentations (p = 0.737) between the genders. The majority of female first-author submissions involved pediatric (29.94%) and general (17.88%) otolaryngology.

Conclusion: While women are increasingly drawn to otolaryngology, they represented less than 20% of total submissions at the annual AAO-HNS meetings from 2000 to 2004. Women more commonly submit poster than oral presentations. The eventual publication rates of abstracts and the average time to publication of presentations are equal between the genders.
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http://dx.doi.org/10.1159/000345099DOI Listing
August 2013

Pulse steroid therapy inhibits murine subglottic granulation.

Otolaryngol Head Neck Surg 2013 Feb 21;148(2):284-90. Epub 2012 Nov 21.

Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Objective: Using a functional model of airway granulation tissue in subglottic stenosis, we investigated changes in inflammatory markers within granulation tissue in response to intraperitoneal dexamethasone injections. Changes in inflammatory markers will allow us to identify potential targets for immunological therapy.

Study Design: Institutional Animal Care and Use Committee-approved animal study.

Setting: Philadelphia Veterans Administration Medical Center animal research facility.

Subjects And Methods: Laryngotracheal complexes of donor mice underwent direct airway injury and were transplanted into subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal complexes were then harvested, and granulation formation was measured. The messenger RNA (mRNA) expression of transforming growth factor (TGF)-β(1) and interleukin (IL)-1 was quantified.

Results: At 3 weeks posttransplantation, there were statistically significant differences in observable granulation formation as well as mRNA expression of TGF-β(1) and IL-1β in all groups within the steroid treated arm as compared with the untreated arm.

Conclusions: Systemic steroids have been used to prevent formation of granulation tissue and subglottic stenosis. However, the study of the immunologic markers and the corresponding changes with steroid treatment has not been well studied in animal models. Using a previously described novel murine model, we begin to delineate inflammatory markers that can be applied for potential therapeutic targets.
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http://dx.doi.org/10.1177/0194599812466533DOI Listing
February 2013

Laser ablation of a large tongue hemangioma with remifentanil analgosedation in the ORL endoscopy suite.

ORL J Otorhinolaryngol Relat Spec 2011 25;73(3):166-9. Epub 2011 May 25.

Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

We present a unique, practical, and safe approach to the clinical management of a young male with a large tongue hemangioma who presented for serial surgical treatment of the lesion. Laser ablation was undertaken in the operating room under topical anesthesia with remifentanil analgosedation without the use of supplemental oxygen. Significant involution of the hemangioma was achieved without complication while the patient was awake, cooperative, and able to protect his airway. The application of remifentanil infusion for analgosedation during airway surgery is described. The utility of pharmacokinetic modeling in these applications is discussed along with the use of non-invasive respiratory inductance plethysmography to monitor ventilation during opioid sedation. The concept of analgosedation for airway surgery is introduced and relative risk versus benefit considerations of the approach in comparison to general anesthesia are discussed. This approach can be conceived of as an ORL endoscopy suite model for limited airway procedures.
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http://dx.doi.org/10.1159/000328341DOI Listing
October 2011

Cellular adaptive inflammation mediates airway granulation in a murine model of subglottic stenosis.

Otolaryngol Head Neck Surg 2011 Jun 18;144(6):927-33. Epub 2011 Feb 18.

Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Objective: To determine the contribution of B- and T-cell-mediated inflammation in a murine airway granulation model.

Study Design: Pilot study in a modified murine model.

Setting: Philadelphia VA Medical Center Research Building.

Subjects And Methods: Laryngotracheal complexes (LTCs) from 54 donor C57BL/6 mice were harvested and divided into 3 groups: (1) uninjured, (2) mechanically injured using a wire brush, and (3) chemically injured using hydrochloric acid. One donor LTC from each group was placed in deep dorsal subcutaneous pockets of either severe combined immunodeficiency (SCID)- or C57BL-recipient mice, for a total of 3 transplanted tracheas per recipient mouse. After 3 weeks, the transplanted LTCs were harvested from both C57BL- and SCID-recipient mice. Tissues were fixed, sectioned, and stained with hematoxylin and eosin. Representative slides were reviewed by a blinded pathologist to determine the formation of granulation tissue and graded as to the degree of formation of granulation tissue.

Results: Despite significant granulation formation in C57BL-recipient mice, direct airway injury did not induce the formation of granulation tissue under the disrupted epithelium of airway mucosa in SCID mice 3 weeks after injury.

Conclusion: The data indicate that the immune response that results in the formation of granulation tissue is mediated by circulating B- and/or T-cell processes rather than resident airway immune cells. Further studies focusing on cellular adaptive immune processes in response to airway injury may provide a novel treatment modality for subglottic stenosis.
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http://dx.doi.org/10.1177/0194599810397750DOI Listing
June 2011

Quality of life and self-image in patients undergoing tracheostomy.

Laryngoscope 2010 ;120 Suppl 4:S196

Department of General Surgery, University of Pennsylvania, PA, USA.

Objectives: The objective of this study is to understand trends in the Quality of Life and Self Image in patients undergoing an elective tracheostomy for non-malignant laryngeotracheal pathologies. We will also discuss the relationship between quality of life and patient demographics.

Study Design: A prospective, IRB approved cohort study was conducted in a tertiary referral center. The SF-12, was used to assess the mental and physical health of patients. The 12 questions on this tool were scored to generate a Physical Composite Score(PCS) and a Mental Composite Score (MCS). A higher score indicates better health.

Methods: The retrospective arm of the study included patients who presented to the senior author and had a trachesotomy for greater than 6 months. For the prospective arm of the study patients were recruited when they were to undergo an elective tracheostomy. Patients were recruited over a 12 month period. In the prospective arm the questionnaire was administered one to seven days pre-operatively and one to three weeks postoperatively. Variables analyzed included age, gender, marital status, education, occupation and other co-morbidities.

Results: In the prospective group, Mean PCS scores were higher in the post-trach period (38.2 ± 6.9) compared to the pre-trach period (35.4 ± 11.5). However, there is a decline in the MCS score in the post-trach period (49 ± 8.5) compared to the pre-trach period (55.4 ± 7.3). In the retrospective group, Mean PCS scores in this group was 28.5 ± 12.3 while the mean MCS score was 40.5 ± 18.3.

Conclusion: Planned tracheostomy is a beneficial intervention for patients with benign airway pathologies, since they experience an improvement in their physical health and the ability to perform activities of daily living. There is a decline in mental health postoperatively, which we attribute to worsening self esteem. Patients who did not undergo planned tracheostomy as seen in the retrospective group, experienced a decline in their physical and mental functioning. This can be attributed to the lack of understanding of the benefit of the procedure and poor preoperative counseling. We recommend perioperative psychological assessment to improve mental health in patients undergoing elective trachesotomies.
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http://dx.doi.org/10.1002/lary.21663DOI Listing
February 2011