Publications by authors named "Adam J Kimple"

61 Publications

SARS-CoV-2 infection of the oral cavity and saliva.

Nat Med 2021 Mar 25. Epub 2021 Mar 25.

Division of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
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http://dx.doi.org/10.1038/s41591-021-01296-8DOI Listing
March 2021

Prolonged Implantation of Sinus Devices and Implications for Chronic Rhinosinusitis: A Case Report and Review of the Literature.

Surg Case Rep (Tallinn) 2020 Apr 28;3(4). Epub 2020 Apr 28.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States.

Background: Implantation of sinus stents and spacers can be used as adjuvant management to maintain patency of sinuses after endoscopic sinus surgery for chronic rhinosinusitis. These implants are typically removed several weeks after surgery. We present two cases of different patients who were initially treated by different physicians and were found to have retained sinus spacers in their paranasal sinuses 6-10 years after implantation.

Case Presentation: Case 1: a 40-year old male with chronic rhinosinusitis and history of balloon sinuplasty six years prior presented with worsening symptoms of chronic rhinosinusitis refractory to medical management. He underwent revision functional endoscopic sinus surgery and was found to have retained sinus implants in the left and right frontal sinus recesses. Case 2: a 48-year-old female with long-standing chronic rhinosinusitis refractory to medical management presented after two prior sinus surgeries most recently 10 years ago. She underwent revision functional endoscopic surgery and was found to have a retained sinus implant from prior surgery in the right frontal recess outflow tract embedded within scar tissue and reactive hyperostosis. Foreign bodies from both patients were removed without complication and patients were healing appropriately in the post-operative period.

Conclusions: While sinus stents and spacers can help with post-operative scarring, leaving then unmonitored and in place will eventually result in them becoming a nidus for scarring and infection. It is critical that patients are aware of any foreign bodies we place, if they need scheduled removal or routine observation, and what symptoms may indicate that they are causing a problem.
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http://dx.doi.org/10.31487/j.scr.2020.04.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771652PMC
April 2020

Quantification of Aerosol Concentrations During Endonasal Instrumentation in the Clinic Setting.

Laryngoscope 2021 05 5;131(5):E1415-E1421. Epub 2020 Oct 5.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.

Objective: Recent anecdotal reports and cadaveric simulations have described aerosol generation during endonasal instrumentation, highlighting a possible risk for transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during endoscopic endonasal instrumentation. This study aims to provide a greater understanding of particle generation and exposure risk during endoscopic endonasal instrumentation.

Study Design: Prospective quantification of aerosol generation during office-based nasal endoscopy procedures.

Methods: Using an optical particle sizer, airborne particles concentrations 0.3 to 10 microns in diameter, were measured during 30 nasal endoscopies in the clinic setting. Measurements were taken at time points throughout diagnostic and debridement endoscopies and compared to preprocedure and empty room particle concentrations.

Results: No significant change in airborne particle concentrations was measured during diagnostic nasal endoscopies in patients without the need for debridement. However, significant increases in mean particle concentration compared to preprocedure levels were measured during cold instrumentation at 2,462 particles/foot (95% CI 837 to 4,088; P = .005) and during suction use at 2,973 particle/foot (95% CI 1,419 to 4,529; P = .001). In total, 99.2% of all measured particles were ≤1 μm in diameter.

Conclusion: When measured with an optical particle sizer, diagnostic nasal endoscopy with a rigid endoscope is not associated with increased particle aerosolization in patient for whom sinonasal debridement is not needed. In patients needing sinonasal debridement, endonasal cold and suction instrumentation were associated with increased particle aerosolization, with a trend observed during endoscope use prior to tissue manipulation. Endonasal debridement may potentially pose a higher risk for aerosolization and SARS-CoV-2 transmission. Appropriate personal protective equipment use and patient screening are recommended for all office-based endonasal procedures.

Level Of Evidence: 3 Laryngoscope, 131:E1415-E1421, 2021.
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http://dx.doi.org/10.1002/lary.29122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675733PMC
May 2021

Quantification of Aerosol Particle Concentrations During Endoscopic Sinonasal Surgery in the Operating Room.

Am J Rhinol Allergy 2020 Oct 4:1945892420962335. Epub 2020 Oct 4.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Recent indirect evidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission during endoscopic endonasal procedures has highlighted the dearth of knowledge surrounding aerosol generation with these procedures. As we adapt to function in the era of Coronavirus Disease 2019 (COVID-19) a better understanding of how surgical techniques generate potentially infectious aerosolized particles will enhance the safety of operating room (OR) staff and learners.

Objective: To provide greater understanding of possible SARS-CoV-2 exposure risk during endonasal surgeries by quantifying increases in airborne particle concentrations during endoscopic sinonasal surgery.

Methods: Aerosol concentrations were measured during live-patient endoscopic endonasal surgeries in ORs with an optical particle sizer. Measurements were taken throughout the procedure at six time points: 1) before patient entered the OR, 2) before pre-incision timeout during OR setup, 3) during cold instrumentation with suction, 4) during microdebrider use, 5) during drill use and, 6) at the end of the case prior to extubation. Measurements were taken at three different OR position: surgeon, circulating nurse, and anesthesia provider.

Results: Significant increases in airborne particle concentration were measured at the surgeon position with both the microdebrider (p = 0.001) and drill (p = 0.001), but not for cold instrumentation with suction (p = 0.340). Particle concentration did not significantly increase at the anesthesia position or the circulator position with any form of instrumentation. Overall, the surgeon position had a mean increase in particle concentration of 2445 particles/ft3 (95% CI 881 to 3955; p = 0.001) during drill use and 1825 particles/ft3 (95% CI 641 to 3009; p = 0.001) during microdebrider use.

Conclusion: Drilling and microdebrider use during endonasal surgery in a standard operating room is associated with a significant increase in airborne particle concentrations. Fortunately, this increase in aerosol concentration is localized to the area of the operating surgeon, with no detectable increase in aerosol particles at other OR positions.
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http://dx.doi.org/10.1177/1945892420962335DOI Listing
October 2020

A Comparison of Sphenoid Sinus Osteoneogenesis in Aspirin-Exacerbated Respiratory Disease.

Am J Rhinol Allergy 2021 Mar 13;35(2):172-178. Epub 2020 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized.

Objective: The aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls.

Methods: A retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists.

Results: Patients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05).

Conclusion: Patients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis.
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http://dx.doi.org/10.1177/1945892420941732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874380PMC
March 2021

Radiologic Analysis of Balloon Sinuplasty in a Human Cadaver Model: Observed Effects on Sinonasal Anatomy.

Am J Rhinol Allergy 2021 Jan 7;35(1):107-113. Epub 2020 Jul 7.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina Chapel Hill, Chapel Hill, North Carolina.

Background: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature.

Objective: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model.

Methods: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically.

Results: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time.

Conclusions: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.
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http://dx.doi.org/10.1177/1945892420939430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874344PMC
January 2021

Numerical evaluation of spray position for improved nasal drug delivery.

Sci Rep 2020 06 29;10(1):10568. Epub 2020 Jun 29.

Department of Otolaryngology/Head and Neck Surgery, School of Medicine - University of North Carolina, Chapel Hill, NC, 27599, United States.

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.
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http://dx.doi.org/10.1038/s41598-020-66716-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324389PMC
June 2020

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort.

Am J Rhinol Allergy 2021 Jan 19;35(1):72-76. Epub 2020 Jun 19.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms.

Methods: We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified.

Results: The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17-53 years old. The volumes for all thee sinus cavities were significantly smaller (p < 0.007) compared to the control population. The average Lund-Mackay score was 10.6 in the PCD cohort (range 6-16) in comparison to an average of 0.7 in the control cohort (range 0-2).

Conclusions: Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group.
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http://dx.doi.org/10.1177/1945892420933175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750665PMC
January 2021

Extramedullary Hematopoiesis in the Sinonasal Cavity: A Case Report and Review of the Literature.

Allergy Rhinol (Providence) 2020 Jan-Dec;11:2152656720918874. Epub 2020 Apr 21.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina.

Background: Extramedullary hematopoiesis (EMH) occurs in patients with hematologic disorders, but rarely within the paranasal sinuses. We report a case of EMH in a 17-year-old male with sickle cell disease (SCD) who presented with occipital pain and sinusitis. A computed tomography (CT) scan demonstrated heterogeneous opacification of the right maxillary sinus concerning for allergic fungal sinusitis or a fungal ball with bony erosion. He was taken to the operating room for endoscopic biopsy and a limited endoscopic sinus surgery. Grossly, his maxillary sinus was filled with spiculated osseous tissue. Final pathology demonstrated active hematopoietic bone marrow filling the sinus.

Methods: We present a case report and literature review of sinonasal EMH.

Results: We identified 14 articles with 15 patients. EMH was typically associated with SCD or beta thalassemia. The average age of presentation was 30. There was a male sex predilection with a ratio of 11:15. The most common presenting symptom was a headache and nasal obstruction (33% for both). The most common finding on CT was a soft tissue expansile mass (73%). The most commonly affected location was the maxillary sinus (60%).

Conclusions: This case report serves as a reminder to consider EMH as an uncommon cause of sinus opacification, particularly in patients with SCD or beta thalassemia. The expansion of hematopoietic tissue may be identified as a sinus mass on CT. By recognizing the potential manifestations of chronic anemia, an accurate and timely diagnosis can be made.
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http://dx.doi.org/10.1177/2152656720918874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177988PMC
April 2020

Understood? Evaluating the readability and understandability of intranasal corticosteroid delivery instructions.

Int Forum Allergy Rhinol 2020 06 13;10(6):773-778. Epub 2020 Apr 13.

Department of Otolaryngology/Head and Neck Surgery, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: Allergic rhinitis is a widespread disease that has significant quality-of-life ramifications. Symptoms include rhinorrhea, nasal obstruction, cough, and postnasal drip. Intranasal corticosteroids are a hallmark of treatment of allergic rhinitis. However, the benefits of treatment are dependent on correct nasal spray technique, of which many patients are not aware. Patient instructions are included with the purchase of these medications. The readability and understandability for these educational materials has been minimally assessed in the medical literature. The aim of this study was to evaluate the readability and understandability of commonly used intranasal steroids.

Methods: Three readability measures (Gunning Fog, Simple Measure of Gobbledygook [SMOG], and FORCAST) and an understandability assessment (Patient Education Materials Assessment Tool for Printable Materials [PEMAT-P]) were used to evaluate the instructions for use of commonly prescribed intranasal steroids. Instructions with 6th grade readability level or lower were considered to meet health literacy experts' recommendations. Higher understandability values correlate to easier understandability.

Results: Instructions for 10 intranasal corticosteroid brands were reviewed. Gunning Fog consistently estimated easiest readability, whereas FORCAST estimated most difficult readability. Twenty percent (20%) of analyzed instructions met National Institutes of Health and health literacy experts' recommended reading levels. Understandability of instructions ranged from 33% to 90%, with an average of 66%.

Conclusion: The benefit of intranasal corticosteroids is contingent on correct use by patients. However, the prepackaged instructions provided are most often above recommended reading levels and are difficult to understand. Future development of intranasal steroid instructions should meet recommended readability levels and be understandable to maximize their utility.
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http://dx.doi.org/10.1002/alr.22550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266716PMC
June 2020

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist.

Am J Rhinol Allergy 2020 Jul 13;34(4):573-580. Epub 2020 Mar 13.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described.

Objective: Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF.

Methods: The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed.

Results: Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators' increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS.

Conclusions: CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.
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http://dx.doi.org/10.1177/1945892420912368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573678PMC
July 2020

Streamlining care in cystic fibrosis: survey of otolaryngologist, pulmonologist, and patient experiences.

Int Forum Allergy Rhinol 2020 05 17;10(5):591-603. Epub 2020 Jan 17.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: Care coordination for cystic fibrosis (CF) is essential. The objectives of this study were to: (1) compare otolaryngologists' and pulmonlogists' understanding of long-term chronic rhinosinusitis (CRS) management; and (2) query patient perceptions of otolaryngologic care and CRS.

Methods: A cross-sectional survey was administered by the Cystic Fibrosis Foundation in 2018 to patients with CF or their caregivers, otolaryngologists, and pulmonologists. Statistical analysis was performed comparing specialists. Descriptive statistics were computed for patient/caregiver-reported data.

Results: Respondents included 126 otolaryngologists, 115 pulmonologists, and 186 patients with CF or their caregivers. Pulmonologists had greater experience caring for CF patients compared with otolaryngologists (66.7% vs 43.2% with 13 years of experience, respectively), but more otolaryngologists cared for both adult and pediatric CF patients (39.2% vs 10.4%, respectively). Significantly more otolaryngologists advocated for establishing otolaryngologic care at time of CF diagnosis (64.8%) compared with pulmonologists (14.4%, p < 0.001), of whom 60.4% recommended otolaryngologist referral when sinonasal symptoms affect quality of life. More otolaryngologists perceived sinus surgery as beneficial for pulmonary function (74.5% vs 57.7%, p = 0.009); 60.8% of patients first sought otolaryngologic care in infancy or childhood (<13 years). Median number of sinus surgeries was 3 (interquartile range, 2-5). The most common perceived benefits of surgery according to patients/caregivers included improved breathing (31.2%) and improved sinonasal symptoms (23.7%). Top patients/caregiver otolaryngologic priorities included symptom/infection control (49.0%) and care coordination (15.0%).

Conclusion: Our results highlight variable patient/caregiver experiences, and suggest that otolaryngologist and pulmonologist perceptions of CF otolaryngologic care also differ in some respects requiring improved interspecialty coordination/education.
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http://dx.doi.org/10.1002/alr.22522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278084PMC
May 2020

Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Case Report and Review of the Literature.

Allergy Rhinol (Providence) 2019 Jan-Dec;10:2152656719889030. Epub 2019 Nov 20.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors which most often arise from the minor salivary glands primarily in palate and tongue but can arise in any location with minor salivary glands including the nasopharynx.

Methods: A case report of primary nasopharyngeal HCCC is presented. Because of the rarity of this tumor and location, a literature search was conducted to determine the most common presenting symptoms, treatment strategies, and outcomes.

Results: A 48-year-old man underwent biopsy of a 4.5 cm mass of the right nasopharynx with pathology suggesting an intermediate grade mucoepidermoid carcinoma. After discussing management with the patient, an endoscopic resection was performed. Final pathology revealed an HCCC which was confirmed after negative Mastermind-like 2 (MAML2) and positive Ewing sarcoma breakpoint region 1 (ESWR1) gene rearrangements on fluorescence in situ hybridization (FISH) studies. Literature review of other nasopharyngeal HCCC cases shows diverse presentation and overall excellent prognosis through surgical and radiation therapy.

Conclusion: HCCCs are rare, low-grade malignant tumors of the minor salivary glands and can present as a nasopharyngeal mass. Presenting symptoms are diverse but frequently involve otologic and sinonasal disturbances. HCCC is an indolent tumor with an excellent prognostic outcome when treated appropriately with surgical resection and adjuvant radiotherapy.
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http://dx.doi.org/10.1177/2152656719889030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883668PMC
November 2019

Mometasone absorption in cultured airway epithelium.

Int Forum Allergy Rhinol 2019 12 21;9(12):1451-1455. Epub 2019 Oct 21.

Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: Topical mometasone is frequently used as an intranasal spray, on drug-eluting stents, and compounded by specialty pharmacies as a sinus rinse. A typical sinus rinse contains 1.2 mg of mometasone dissolved in 240 mL of buffered saline and is flushed through the sinonasal cavity. The mometasone irrigation rapidly flows to the contralateral sinonasal cavity or the nasopharynx with a contact time on the order of 5 to 10 seconds. However, no information is available on the absorption rate of topical mometasone on the sinonasal surface.

Methods: To determine the absorption characteristics of mometasone, we harvested nasal epithelium from 2 healthy donors and differentiated them into a mature ciliated epithelium on Millicell membranes. We applied mometasone to the apical surface for various time intervals and then rinsed off non-absorbed mometasone with phosphate-buffered saline. Millicell membranes with the adherent epithelial cells were then harvested and stored in guanidine hydrochloride for quantification using high-performance liquid chromatography-mass spectrometry.

Results: Fifty percent of the maximal absorption occurred after an average of 38 minutes after application, and maximal absorption occurred after an average of 114 minutes.

Conclusion: Our data provide an estimate for rates of absorption of mometasone applied to the sinonasal cavity and suggest that the absorption rates poorly match contact time during saline lavage.
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http://dx.doi.org/10.1002/alr.22441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927533PMC
December 2019

Readability of patient-reported outcome measures for chronic rhinosinusitis and skull base diseases.

Laryngoscope 2020 10 11;130(10):2305-2310. Epub 2019 Oct 11.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, U.S.A.

Objective: Outcome measures in healthcare that presume a higher level of patient health and overall literacy may inadequately estimate the disease experiences of less-educated patients and further disadvantage them. Patient-Reported Outcome Measures (PROMs) are widely used communication tools for clinical practice and are often used to evaluate and guide management for chronic rhinosinusitis (CRS) and skull base diseases. However, their readability and subsequent incomprehensibility for patients have not been assessed. The aim of this study is to evaluate the readability of commonly used PROMs for these conditions and whether they meet recommended readability levels.

Methods: Three readability measures, Gunning Fog, Simple Measure of Gobbledygook (SMOG), and FORCAST were used in the evaluation of commonly used PROMs for CRS and skull base disease. PROMs with sixth-grade readability level or lower were considered to meet health literacy experts' recommendations.

Results: A total of 11 PROMs were reviewed (8 CRS, 3 skull base). Gunning Fog consistently estimated the easiest readability, whereas FORCAST the most difficult. One hundred percent of CRS and 67% of skull base PROMs were above National Institutes of Health and health literacy experts' recommended reading levels. PROMs developed more recently had easier readability.

Conclusion: PROMs are important clinical tools in otolaryngology that help guide management of disease for improved patient-centered care. Like many other fields of medicine, those used in otolaryngology are beyond recommended reading levels. Development of PROMs in the future should meet recommended readability levels to fully assess the disease experience of our patients.

Level Of Evidence: 4 Laryngoscope, 130:2305-2310, 2020.
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http://dx.doi.org/10.1002/lary.28330DOI Listing
October 2020

Modeling Microdebrider-Mediated Ophthalmic Damage: A Word of Caution in Endoscopic Sinus Surgery.

Rhinol Online 2019 7;2:44-49. Epub 2019 Mar 7.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: The microdebrider has become nearly universal in the treatment of sinonasal pathology; however, recent case reports have demonstrated the potential for major ophthalmic complications. The goal of this study was twofold: 1) determine the anatomical proximity of ophthalmic structures to the paranasal sinuses, and 2) assess the timeframe at which ophthalmic injury may occur with the use of a microdebrider during FESS utilizing a cadaveric model.

Methodology/principal: Computed tomography scans from 50 patients were accessed retrospectively. The distances between the lamina papyracea (LP) and orbital structures were determined at varying depths. Seven cadavers (14 sides) were studied using three microdebrider systems operated by otolaryngology residents. Following removal of a window of LP, the time from activation of the microdebrider on the periorbita until transection of the medial rectus (MR), optic nerve (ON), and to aspiration of the globe were measured.

Results: The mean distance between the LP and MR at the level of the anterior aspect of the anterior ethmoid and basal lamella were 3.59 ±1.2mm and 1.5 ±0.8mm, respectively. The mean distance between the LP and ON at the level of the basal lamella was 8.1 ±2.1mm. Mean transection times for the MR and ON were 13.4 ± 7.3 seconds and 37.3 ± 9.2 seconds, respectively, with minimum times of 4 seconds and 26 seconds.

Conclusions: The proximity of orbital structures to the paranasal sinuses and the rapidity of ophthalmic damage following violation of the periorbita reaffirms the need for cautious use of the microdebrider during FESS.
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http://dx.doi.org/10.4193/RHINOL/19.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748634PMC
March 2019

The Adolescent Vaping Epidemic in the United States-How It Happened and Where We Go From Here.

JAMA Otolaryngol Head Neck Surg 2019 Aug 22. Epub 2019 Aug 22.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill.

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http://dx.doi.org/10.1001/jamaoto.2019.2410DOI Listing
August 2019

Image quality and dose reduction in sinus computed tomography using iterative reconstruction: a cadaver study.

Rhinol Online 2018 ;1:45-49

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, USA.

Background: Concerns about radiation dose in computed tomography (CT) imaging have renewed interest in iterative reconstruction (IR), a technique which has the potential to produce images with less noise at lower radiation doses than traditional filtered back projection (FBP). This study aimed to assess whether application of IR could provide comparable quality sinus CT images to FBP at lower kilovolt (kV) and milliamp (mA) settings, and to establish optimal scan settings for sinus imaging.

Methodology/principal: 30 sinus CT scans were performed on 5 cadaver heads at two kV setting and three mA settings. Each scan was reconstructed using FBP and 3 IR settings, yielding a total of 120 images series. Each image set was blinded and randomly reviewed by 3 rhinologists and 2 neuroradiologists. Using a 5-point Likert scale, 16 anatomical landmarks, were graded with respect to image quality. Data were assessed with respect to dose and IR settings using statistical analysis.

Results: Higher kV and mAs settings produced significantly higher quality images for structure identification across all 16 landmarks; however, the suitability for surgery did not increase in a linear fashion and plateaued by a total radiation dose of 0.1201 mSv. IR algorithm did not provide a benefit in the overall score of scans at a fixed kV and mAs.

Conclusions: Identification of structures in sinus CT imaging significantly correlate with the kV and mA and overall dose of radiation; however, IR did not provide additional benefit in the image quality.
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http://dx.doi.org/10.4193/RHINOL/18.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292212PMC
January 2018

How Much Blood Could a JP Suck If a JP Could Suck Blood?

Laryngoscope 2019 08 13;129(8):1806-1809. Epub 2018 Dec 13.

Department of Otolaryngology Head and Neck Surgery at Chapel Hill, Chapel Hill, North Carolina, U.S.A.

Objective: Active surgical drains minimize fluid accumulation in the postoperative period. The Jackson-Pratt (JP) system consists of a silicone drain connected by flexible tubing to a bulb. When air in the bulb is evacuated, negative pressure is applied at the surgical site to aspirate fluid. The objective of this study was to determine if the evacuation method and volume of accumulated fluid affect the pressure generated by the bulb.

Methods: Bulbs were connected to a digital manometer under various experimental conditions. A random number generator determined the initial evacuation method for each bulb, either side-in or bottom-up. Subsequent evacuations were alternated until data was collected in triplicate for each method. Predetermined amounts of water were placed into the bulb; air was evacuated; and pressure was recorded. The digital manometer was allowed to equilibrate for 1 minute prior to data acquisition.

Results: The average amount of pressure after a side-in evacuation of a JP bulb was 87.4 cm H O compared to 17.7 cm H O for a bottom-up evacuation (P < 0.0001). When the drain contained 25 mL, 50 mL, 75 mL, and 100 mL of fluid, the pressure applied dropped to 72.6, 41.3, 37.0, and 35.6 cm H O, respectively.

Conclusions: JP drains generate negative pressure in order to reduce fluid accumulation at surgical sites. Although its function is frequently taken for granted, this study demonstrates that both the specific method for evacuating the bulb as well as the amount of fluid in the bulb significantly affect the performance of this device.

Level Of Evidence: NA Laryngoscope, 129:1806-1809, 2019.
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http://dx.doi.org/10.1002/lary.27710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565520PMC
August 2019

Sinonasal epithelial-myoepithelial carcinoma: Report of a novel subsite and review of the literature.

Allergy Rhinol (Providence) 2018 Jan-Dec;9:2152656718764229. Epub 2018 Apr 9.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Background: Epithelial-myoepithelial carcinoma (EMC) is a rare tumor of the major and minor salivary glands. Sinonasal EMC is extremely uncommon and hitherto not described within the frontal or ethmoid sinuses.

Objective: To present a novel sinonasal subsite and review the literature regarding sinonasal EMC.

Methods: A case of frontoethmoidal EMC was presented. A medical literature data base was queried from January 1, 1950, to August 8, 2017, for all reports of sinonasal EMC.

Results: A 69-year-old man underwent combined open and endoscopic craniofacial resection of a right frontoethmoidal EMC, a previously undescribed primary location for this tumor. A comprehensive review of the literature revealed 13 additional cases of sinonasal EMC.

Conclusion: EMC is an uncommon neoplasm typically found in the major salivary glands; occurrence in the nose or paranasal sinuses is extremely rare. EMC often follows an indolent clinical course, although, in a minority of cases, particularly in large tumors with nuclear atypia, more aggressive behavior may be observed.
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http://dx.doi.org/10.1177/2152656718764229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028158PMC
April 2018

Surgical simulation and applicant perception in otolaryngology residency interviews.

Laryngoscope 2018 11 25;128(11):2503-2507. Epub 2018 Apr 25.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, U.S.A.

Objective: The traditional resident applicant interview involves multiple oral interviews. The implementation of surgical simulations adds an additional dimension of assessment but can be perceived in a stressful way by applicants. The purpose of this project is to describe low-fidelity simulations that were implemented for the 2016 to 2017 residency interviews and obtain applicant perception of these simulations.

Methods: Six simulation modules were created, which reflected tasks used in six subspecialties within otolaryngology (pediatrics, otology, laryngology, facial plastics, rhinology, and head/neck). Applicants were guided in the procedures by both an attending and resident. Afterward, applicants were anonymously surveyed on their perception of the tasks using a 5-point Likert scale (1 = Strongly Disagree, 2 = Somewhat Disagree, 3 = Neutral, 4 = Somewhat Agree, 5 = Strongly Agree).

Results: A total of 41 applicants were interviewed. The following were measured: enjoyable (98.5% strongly agree, 2.5% somewhat agree; mean: 4.97; 95% confidence interval [CI], 4.92, 5.02), educational (88% strongly agree, 12% somewhat agree; mean: 4.88; 95% CI, 4.78, 4.98), recommended for future use (92.7% strongly agree, 7.3% somewhat agree; mean: 4.93; 95% CI, 4.85, 5.01), and stressful (63.5% strongly disagree, 19.5% somewhat disagree, 17% neutral; mean: 1.54; 95% CI, 1.30, 1.78).

Conclusion: Implementation of a low-fidelity multi-station surgical simulation experience is feasible in an interview day. Majority of applicants viewed the simulations in a positive manner. Surgical simulations may provide a useful holistic evaluation of an applicant in future interviews, especially if done in a setting that minimizes stress and maximizes the educational experience.

Level Of Evidence: 2b. Laryngoscope, 2503-2507, 2018.
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http://dx.doi.org/10.1002/lary.27211DOI Listing
November 2018

Aggressive Tumor, Aggressive Treatment.

Int J Radiat Oncol Biol Phys 2017 12;99(5):1062-1063

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.ijrobp.2017.07.027DOI Listing
December 2017

Pneumocephalus after insertion of an inflatable nasal tampon for the management of epistaxis.

Ear Nose Throat J 2016 Apr-May;95(4-5):172-4

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina Memorial Hospitals, 170 Manning Dr., Ground Floor, Physician Office Building, CB #7070, Chapel Hill, NC 27599, USA.

While the fundamental principles of epistaxis management have not changed over the decades, the methods by which tamponade is achieved have been evolving. Inflatable nasal tampons are being used and seen with increasing frequency in our ENT clinic. They are usually placed by emergency department personnel, who then refer patients to our clinic for removal. The classically described complications of nasal packs are induction of the nasopulmonary reflex, toxic shock syndrome, and discomfort. In this article, we describe a case of pneumocephalus following placement of an inflatable nasal tampon. To the best of our knowledge, this is the first report of pneumocephalus after placement of an inflatable nasal tampon.
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April 2017

Standardized letters of recommendation and successful match into otolaryngology.

Laryngoscope 2016 05 3;126(5):1071-6. Epub 2016 Feb 3.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.

Objectives/hypothesis: Historically, narrative letters of recommendation have been utilized in the selection of applicants for otolaryngology residency programs. In the last two application cycles, our specialty adopted a standardized letter of recommendation (SLOR). The intent was to decrease time burden for letter writers and to provide readers with an objective evaluation of applicants. The objective of this study was to determine attributes in the SLOR that correlate with matching into a residency program.

Study Design: We performed a retrospective study using SLOR, United States Medical Licensing Examination (USMLE) step 1 scores, and matched outcomes of applicants who applied to our institution for the 2013 and 2014 match cycle.

Methods: We included the following variables from the SLOR in the statistical analysis to determine which ones were associated with matching: patient care, medical knowledge, communication skills, procedural skills, research, initiative and drive, commitment to otolaryngology, commitment to academic medicine, match potential, and USMLE1 scores.

Results: We identified 532 applicants and 963 SLOR. In successful applicants, scores for patient care, medical knowledge, communication skills, initiative and drive, and match potential were statistically higher (P < 0.05). Scores for professionalism, procedural skills, research, commitment to otolaryngology, commitment to academic medicine, and USMLE step 1 scores were not higher among successfully matched applicants.

Conclusion: Although SLOR can save time for letter writers and provide an objective description of applicants, the utility of individual domains within the SLOR is questionable. Additionally, it is concerning that applicants' professionalism and procedural skills are not correlated with matching in our specialty.

Level Of Evidence: NA. Laryngoscope, 126:1071-1076, 2016.
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http://dx.doi.org/10.1002/lary.25637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842134PMC
May 2016

Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review.

Pediatr Pulmonol 2016 Feb 29;51(2):115-32. Epub 2015 Sep 29.

Department of Pediatrics, University of North Carolina, Marsico Lung Institute, Chapel Hill, North Carolina.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung disease resulting in chronic oto-sino-pulmonary disease in both children and adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their differential diagnosis due to inexperience with diagnostic testing methods. Thus far, all therapies used for PCD are unproven through large clinical trials. This review article outlines consensus recommendations from PCD physicians in North America who have been engaged in a PCD centered research consortium for the last 10 years. These recommendations have been adopted by the governing board of the PCD Foundation to provide guidance for PCD clinical centers for diagnostic testing, monitoring, and appropriate short and long-term therapeutics in PCD patients.
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http://dx.doi.org/10.1002/ppul.23304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912005PMC
February 2016

Oral cavity squamous cell carcinoma--an overview.

Oral Health Dent Manag 2014 Sep;13(3):877-82

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina Memorial Hospitals, 170 Manning Dr., Ground Floor Physician Office Building, CB#7070, Chapel Hill, NC 27599, USA; Tel: 919-966-6484; Fax: 919-966-7941; e-mail:

Inhaled or chewed tobacco is equally addictive and harmful and used daily by over 1 billion people. In addition to increased rates of coronary artery disease, stroke, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease and lung cancers, tobacco is the leading preventable cause of oral cavity squamous cell carcinoma. In addition to tobacco, consumption and abuse of alcohol, and betel nut quid significantly contribute to the burden of oral cavity squamous cell carcinoma. Dental visits are excellent opportunities to identify primary lesions in the oral cavity. This review highlights relevant anatomy, epidemiology, pathogenesis, evaluation and treatment options for oral cavity squamous cell carcinoma.
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September 2014

Polysomnographic results of prone versus supine positioning in micrognathia.

Int J Pediatr Otorhinolaryngol 2014 Dec 6;78(12):2056-9. Epub 2014 Sep 6.

Division of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Division of Pediatric Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, United States. Electronic address:

Background: Children with micrognathia commonly present with upper airway symptoms and are at risk for developing obstructive sleep apnea (OSA). Prone positioning is widely used as first-line management for micrognathic children with obstructive symptoms. The aim of the present study was to document the effect of positioning on oxygenation and upper airway obstruction as measured by polysomnography (PSG).

Methods: Three children with micrognathia from two institutions underwent PSG in both the prone and supine position.

Results: Patient ages were 1 week, 3 months, and 7 months. Supine obstructive apnea-hypopnea indices (oAHI) were severe for all 3 children, with a mean of 21.9 events/hour (range 16.8 to 26.3). In the prone position, the oAHI significantly improved in 2 of 3 children, with a mean of 5.1 events/hour (range 0.3 to 10.3). The frequency of central apnea events increased in 1 child following supine positioning. Nadir oxygen saturation improved in 2 of 3 children and remained within normal limits in the third.

Conclusions: This is the first report of the effect of positioning on changes in PSG indices of micrognathic children. Improvement in obstructive PSG indices occurred with prone positioning, though OSA persisted in 2 of 3 children. The effect of positioning on central apnea was unclear. In light of these findings, we recommend that routine PSG be considered in micrognathic children undergoing prone positioning for definitive therapy of upper airway obstruction.
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http://dx.doi.org/10.1016/j.ijporl.2014.08.042DOI Listing
December 2014

Polymorphous low-grade adenocarcinoma: a case series and determination of recurrence.

Laryngoscope 2014 Dec 17;124(12):2714-9. Epub 2014 Sep 17.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.

Objectives/hypothesis: Information on polymorphous low-grade adenocarcinoma (PLGA) consists primarily of case reports and small institutional series with varying recurrence rates. In this report, we describe our institutional experience and conduct a review of the literature to assess the overall incidence of PLGA among oral salivary gland tumors and determine recurrence rates.

Study Design: A retrospective case series and literature-based review was performed.

Methods: Retrospective case series at an academic tertiary referral center. Review of clinical records and pathological analysis of tissue specimens from 20 patients treated for PLGA from July 1, 1990 to July 1, 2011. A literature-based review on PLGA was also performed.

Results: Twenty patients (mean age, 54 years; eight males) with PLGA based on pathologic diagnosis were included. The most common initial presentation was an asymptomatic mass (45%), and the most frequent site was the palate (60%). Our literature review identified 54 case reports, eight case series, and 17 large series. In total, 456 cases of PLGA were identified, with an overall recurrence rate of 19%. Half of the recurrences occurred by 36 months; however, recurrences were reported up to 24 years after initial resection.

Conclusions: PLGA arises from minor salivary glands and is characteristically slow growing and indolent. Although these tumors may be histologically low-grade, our review highlights the high rates of recurrence of these tumors as well as the ability to metastasize to local lymph nodes and distant organs. The mainstay of treatment should be wide surgical excision with long-term oncologic follow-up.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lary.24788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547589PMC
December 2014

Surgical treatments for otitis media with effusion: a systematic review.

Pediatrics 2014 Feb 6;133(2):296-311. Epub 2014 Jan 6.

Division for Health Services and Social Policy Research, RTI International, Research Triangle Park, North Carolina; and.

Background And Objective: The near universality of otitis media with effusion (OME) in children makes a comparative review of treatment modalities important. This study's objective was to compare the effectiveness of surgical strategies currently used for managing OME.

Methods: We identified 3 recent systematic reviews and searched 4 major electronic databases. Eligible studies included randomized controlled trials, nonrandomized trials, and cohort studies that compared myringotomy, adenoidectomy, tympanostomy tubes (tubes), and watchful waiting. Using established criteria, pairs of reviewers independently selected, extracted data, rated risk of bias, and graded strength of evidence of relevant studies. We incorporated meta-analyses from the earlier reviews and synthesized additional evidence qualitatively.

Results: We identified 41 unique studies through the earlier reviews and our independent searches. In comparison with watchful waiting or myringotomy (or both), tubes decreased time with OME and improved hearing; no specific tube type was superior. Adenoidectomy alone, as an adjunct to myringotomy, or combined with tubes, reduced OME and improved hearing in comparison with either myringotomy or watchful waiting. Tubes and watchful waiting did not differ in language, cognitive, or academic outcomes. Otorrhea and tympanosclerosis were more common in ears with tubes. Adenoidectomy increased the risk of postsurgical hemorrhage.

Conclusions: Tubes and adenoidectomy reduce time with OME and improve hearing in the short-term. Both treatments have associated harms. Large, well-controlled studies could help resolve the risk-benefit ratio by measuring acute otitis media recurrence, functional outcomes, quality of life, and long-term outcomes. Research is needed to support treatment decisions in subpopulations, particularly in patients with comorbidities.
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http://dx.doi.org/10.1542/peds.2013-3228DOI Listing
February 2014

RGS21, a regulator of taste and mucociliary clearance?

Laryngoscope 2014 Mar 2;124(3):E56-63. Epub 2013 Oct 2.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina at Chapel Hill, North Carolina, U.S.A; Department of Pharmacology, University of North Carolina at Chapel Hill, North Carolina, U.S.A.

Objectives/hypothesis: Motile cilia of airway epithelial cells help to expel harmful inhaled material. Activation of bitterant-responsive G protein-coupled receptors (GPCRs) is believed to potentiate cilia beat frequency and mucociliary clearance. In this study, we investigated whether regulator of G protein signaling-21 (RGS21) has the potential to modulate signaling pathways connected to airway mucociliary clearance, given that RGS proteins modulate GPCR signaling by acting as GTPase-accelerating proteins (GAPs) for the Gα subunits of heterotrimeric G proteins.

Study Design: This is a pilot investigation to determine if RGS21, a potential tastant specific RGS gene, is expressed in sinonasal mucosa, and to determine its specific Gα substrate using in vitro biochemical assays with purified proteins.

Methods: Rgs21 expression in sinonasal mucosa was determined using quantitative, real-time PCR and a transgenic mouse expressing RFP from the Rgs21 promoter. Rgs21 was cloned, over-expressed, and purified using multistep protein chromatography. Biochemical and biophysical assays were used to determine if RGS21 could bind and accelerate the hydrolysis of GTP on heterotrimeric Gα subunits.

Results: Rgs21 was expressed in sinonasal mucosa and lingual epithelium. Purified recombinant protein directly bound and accelerated GTP hydrolysis on Gα subunits.

Conclusions: Rgs21 is expressed in sinonasal mucosa, is amenable to purification as a recombinant protein, and can bind to Gα(i/o/q) subunits. Furthermore, RGS21 can accelerate the hydrolysis rate of GTP on Gαi subunits. This provides evidence that RGS21 may be a negative regulator of bitterant responses. Future studies will be needed to determine the physiological role of this protein in mucociliary clearance.
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http://dx.doi.org/10.1002/lary.24326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985343PMC
March 2014